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Pancreatic enzyme replacement therapy for people with cystic fibrosis - PubMed

  • ️Fri Jan 01 2016

Review

Pancreatic enzyme replacement therapy for people with cystic fibrosis

Usha Rani Somaraju et al. Cochrane Database Syst Rev. 2016.

Update in

Abstract

Background: Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review.

Objectives: To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function).

Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016.

Selection criteria: Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations.

Data collection and analysis: Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review.

Main results: One parallel trial and 12 cross-over trials of children and adults with cystic fibrosis were included in the review. The number of participants in each trial varied between 14 and 129 with a total of 512 participants included in the review. All the included trials were for a duration of four weeks. The included trials had mostly an unclear risk of bias from the randomisation process as the details of this were not given; they also mostly had a high risk of attrition bias and reporting bias.We could not combine data from all the trials as they compared different formulations. Findings from individual studies provided insufficient evidence to determine the size and precision of the effects of different formulations. Ten studies reported information on the review's primary outcome (nutritional status); however, we were only able to combine data from two small cross-over studies (n = 41). The estimated gain in body weight was imprecise, 0.32 kg (95% confidence interval -0.03 to 0.67; P = 0.07). Combined data from the same studies gave statistically significant results favouring enteric-coated microspheres over enteric-coated tablets for our secondary outcomes stool frequency, mean difference -0.58 (95% confidence interval -0.85 to -0.30; P < 0.0001); proportion of days with abdominal pain, mean difference -7.96% (95% confidence interval -12.97 to -2.94; P = 0.002); and fecal fat excretion, mean difference -11.79 g (95% confidence interval -17.42 to -6.15; P < 0.0001). Data from another single small cross-over study also favoured enteric-coated microspheres over non-enteric-coated tablets with adjuvant cimetidine in terms of stool frequency, mean difference -0.70 (95% confidence interval -0.90 to -0.50; P < 0.00001).

Authors' conclusions: There is limited evidence of benefit from enteric-coated microspheres when compared to non-enteric coated pancreatic enzyme preparations up to one month. In the only comparison where we could combine any data, the fact that these were cross-over studies is likely to underestimate the level of inconsistency between the results of the studies due to over-inflation of confidence intervals from the individual studies.There is no evidence on the long-term effectiveness and risks associated with pancreatic enzyme replacement therapy. There is also no evidence on the relative dosages of enzymes needed for people with different levels of severity of pancreatic insufficiency, optimum time to start treatment and variations based on differences in meals and meal sizes. There is a need for a properly designed study that can answer these questions.

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Conflict of interest statement

None of the authors has any interests to declare.

Figures

1
1

Forest plot of comparison: 2 ECM versus ECT, outcome: 2.2 Stool frequency [number/day].

2
2

Forest plot of comparison: 2 ECM versus ECT, outcome: 2.3 Abdominal pain [% days].

3
3

Forest plot of comparison: 2 ECM versus ECT, outcome: 2.4 FFE [g/day].

4
4

Forest plot of comparison: 4 ECM (Creon®) versus another ECM, outcome: 4.5 Coefficient of fat absorption [%].

1.1
1.1. Analysis

Comparison 1 ECM versus NECT + adjuvant cimetidine, Outcome 1 Change in weight.

1.2
1.2. Analysis

Comparison 1 ECM versus NECT + adjuvant cimetidine, Outcome 2 Stool frequency.

1.3
1.3. Analysis

Comparison 1 ECM versus NECT + adjuvant cimetidine, Outcome 3 Abdominal pain.

1.4
1.4. Analysis

Comparison 1 ECM versus NECT + adjuvant cimetidine, Outcome 4 FFE.

2.1
2.1. Analysis

Comparison 2 ECM versus ECT, Outcome 1 Change in weight.

2.2
2.2. Analysis

Comparison 2 ECM versus ECT, Outcome 2 Stool frequency.

2.3
2.3. Analysis

Comparison 2 ECM versus ECT, Outcome 3 Abdominal pain.

2.4
2.4. Analysis

Comparison 2 ECM versus ECT, Outcome 4 FFE.

3.1
3.1. Analysis

Comparison 3 ECM versus ECMM, Outcome 1 FFE.

4.1
4.1. Analysis

Comparison 4 ECM (Creon®) versus another ECM, Outcome 1 Change in body weight [kg].

4.2
4.2. Analysis

Comparison 4 ECM (Creon®) versus another ECM, Outcome 2 Stool frequency (number/day).

4.3
4.3. Analysis

Comparison 4 ECM (Creon®) versus another ECM, Outcome 3 Proportion of days with abdominal pain.

4.4
4.4. Analysis

Comparison 4 ECM (Creon®) versus another ECM, Outcome 4 Proportion of days with flatulence.

4.5
4.5. Analysis

Comparison 4 ECM (Creon®) versus another ECM, Outcome 5 Coefficient of fat absorption [%].

5.1
5.1. Analysis

Comparison 5 ECM versus TPE, Outcome 1 FFE.

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References

References to studies included in this review

Assoufi 1994 {published data only}
    1. Assoufi BK, Doig C, Hodson ME. High dose Nutrizym 22 in adults with cystic fibrosis [abstract]. Pediatric Pulmonology 1994;18 Suppl 10:337. [CFGD Register: GN168]
Borowitz 2005 {published data only}
    1. Borowitz D, Goss C, Limauro S, Murray F, Casey S, Cohen M. A dose‐ranging study of efficacy of TheraCLEC‐Total for treatment of pancreatic insufficiency [abstract]. Pediatric Pulmonology 2005;40(Suppl 28):348. [CFGD Register: GN203a]
    1. Borowitz D, Goss CH, Limauro S, Konstan MW, Blake K, Casey S, et al. Study of a novel pancreatic enzyme replacement therapy in pancreatic insufficient subjects with cystic fibrosis. Journal of Pediatrics 2006;149(5):658‐62. [CFGD Register: GN203f] - PubMed
    1. Borowitz D, Goss CH, Limauro S, Murray F, Casey S, Cohen M, et al. A phase 2 study of TheraCLEC‐Total enzymes in CF patients with pancreatic insufficiency (PI) [abstract]. Pediatric Pulmonology 2005;40(Suppl 28):142. [CFGD Register: GN203b]
    1. Borowitz D, Konstan MW, Goss C, Limauro SE, Murray FT. Enhanced coefficient of fat absorption using a novel pancreatic enzyme preparation, ALTU‐135, with concomitant use of a proton pump inhibitor [abstract]. Journal of Cystic Fibrosis 2006;5(Suppl):S56. [CFGD Register: GN203d]
    1. Borowitz D, Konstan MW, Goss C, Limauro SE, Murray FT, Casey S, et al. Treatment with ALTU‐135 results in a positive inverse relationship between coefficient of fat absorption with stool weight in subjects with cystic fibrosis‐related pancreatic insufficiency [abstract]. Journal of Cystic Fibrosis 2006;5(Suppl):S56. [CFGD Register: GN203c]
Elliott 1992 {published data only}
    1. Elliott RB, Escobar LC, Lees HR, Akroyd RM, Reilly HC. A comparison of two pancreatin microsphere preparations in cystic fibrosis. New Zealand Medical Journal 1992;105(930):107‐8. [CFGD Register: GN152] - PubMed
Henker 1987 {published data only}
    1. Henker J, Jutta Hein L, Vogt E. Comparison of effectiveness of Pankreon ForteR and KreonR in children with cystic fibrosis [abstract]. 15th Annual Meeting of the European Working Group for Cystic Fibrosis; 1987; Oslo, Norway. 1987:72. [CFGD Register: GN162]
Lacy 1992 {published data only}
    1. Lacy D, West J, Venkataraman M, Vyas J, MacDonald A, Weller PH, et al. A comparison of Nutrizym GR and Creon in children with CF [abstract]. 11th International Cystic Fibrosis Congress; 1992; Dublin, Ireland. 1992:TP76. [CFGD Register: GN165]
Patchell 1999 {published data only}
    1. Patchell CJ, Desai M, Weller PH, MacDonald A, Smyth RL, Bush A, et al. Creon® 10000 minimicrospheres™ vs. Creon® 8000 microspheres ‐ an open randomised crossover preference study. Journal of Cystic Fibrosis 2002;1(4):287‐91. [CFGD Register: GN189b] - PubMed
    1. Patchell CJ, Smyth RL, Bush A, Weller PW, Collins SA, Gilbody JS. Creon® 10 000 minimicrospheres™ versus Creon® 8000 MS preference study [abstract]. The Netherlands Journal of Medicine 1999;54(Suppl):S64. [CFGD Register: GN189a]
Petersen 1984 {published data only}
    1. Petersen W, Heilman C, Garne S. A double dummy cross‐over study comparing the effect of pancreatic enzyme as acid‐resistant microsphere (Pancrease R Cilag Chemie) to granules (Pancreatin R Rosco) in cystic fibrosis [abstract]. 9th International Cystic Fibrosis Congress; 1984 June 9‐15; Brighton, England. 1984:Poster 8.13. [CFGD Register: GN138a]
    1. Petersen W, Heilmann C, Garne S. Pancreatic enzyme supplementation as acid‐resistant microspheres versus enteric‐coated granules in cystic fibrosis. A double placebo‐ controlled cross‐over study. Acta Paediatrica Scandinavica 1987;76(1):66‐9. [CFGD Register: GN138b] - PubMed
Stead 1986 {published data only}
    1. Stead RJ, Skypala I, Hodson ME, Batten JC. Enteric coated microspheres of pancreatin in the treatment of cystic fibrosis: comparison with a standard enteric coated preparation. Thorax 1987;42(7):533‐7. [CFGD Register: GN140b] - PMC - PubMed
    1. Stead RJ, Skypala I, Hodson ME, Batten JC. Reduction in steatorrhoea in cystic fibrosis using enteric coated microspheres of pancreatin compared with a standard coated preparation [abstract]. 14th Annual Meeting of the European Working Group for Cystic Fibrosis; 1986 Sept 1‐2; Budapest, Hungary. 1986:132. [CFGD Register: GN140a]
Stead 1987 {published data only}
    1. Stead RJ, Skypala I, Hodson ME. Enteric‐coated microspheres of pancreatin versus non enteric‐coated pancreatin combined with cimetidine in cystic fibrosis [abstract]. 15th Annual Meeting of the European Working Group for Cystic Fibrosis; 1987; Oslo, Norway. 1987:71. [CFGD Register: GN146a]
    1. Stead RJ, Skypala I, Hodson ME. Treatment of steatorrhoea in cystic fibrosis: a comparison of enteric‐coated microspheres of pancreatin versus non‐enteric‐coated pancreatin and adjuvant cimetidine. Alimentary Pharmacology & Therapeutics 1988;2(6):471‐82. [CFGD Register: GN146b] - PubMed
Taylor 2015 {published data only}
    1. Taylor CJ, Thieroff‐Ekerdt R, Shiff S, Magnus L, Fleming R, Gommoll C. A randomized, double‐blind, multicentre, multinational crossover comparison of the pancreatic enzyme product (PEP) APT‐1008 (ZENPEP®) to KREON® in the treatment of exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF) in patients ≥12 years of age [abstract]. Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society 2015;14 Suppl 1:S120, Abstract no: 240. [CFGD Register: GN251a; CRS: 5500135000001306]
    1. Taylor CJ, Thieroff‐Ekerdt R, Shiff S, Magnus L, Fleming R, Gommoll C. Comparison of two pancreatic enzyme products for exocrine insufficiency in patients with cystic fibrosis. Journal of Cystic Fibrosis 2016;15(5):675‐80. [CENTRAL: 1157598; CFGD Register: GN251b; CRS: 5500135000001564; DOI: 10.1016/j.jcf.2016.02.010; PUBMED: 27013382] - DOI - PubMed
Vidailhet 1987 {published data only}
    1. Vidailhet M, Derelle J, Morali A, Gasperi JP. Comparison of effectiveness and tolerance of enteric coated versus unprotected pancreatic extracts in CF patients [abstract]. 15th Annual Meeting of the European Working Group for Cystic Fibrosis; 1987; Oslo, Norway. 1987:69. [CFGD Register: GN164]
Vyas 1990 {published data only}
    1. Vyas H, Matthew D, Milla P. A double‐blind comparison between enteric coated microspheres and enteric coated tablets of pancreatic enzymes [abstract]. 14th Annual Meeting of the European Working Group for Cystic Fibrosis; 1986 Sept 1‐2; Budapest, Hungary. 1986:52. [CFGD Register: GN148a]
    1. Vyas H, Matthew DJ, Milla PJ. A comparison of enteric coated microspheres with enteric coated tablet pancreatic enzyme preparations in cystic fibrosis. A controlled study. European Journal of Pediatrics 1990;149(4):241‐3. [CFGD Register: GN148b] - PubMed
Williams 1990 {published data only}
    1. Williams J, MacDonald A, Weller PH, Field J, Pandov H. Enteric‐coated microspheres in cystic fibrosis: Pancrease* vs. Creon [abstract]. Pediatric Pulmonology 1988;5(Suppl 2):143. [CFGD Register: GN149a]
    1. Williams J, MacDonald A, Weller PH, Fields J, Pandov H. Two enteric coated microspheres in cystic fibrosis. Archives of Disease in Childhood 1990;65(6):594‐7. [CFGD Register: GN149b] - PMC - PubMed

References to studies excluded from this review

Ansaldi 1988 {published data only}
    1. Ansaldi Balocco N, Santini B, Sarchi C. Efficacy of pancreatic enzyme supplementation in children with cystic fibrosis: comparison of two preparations by random crossover study and a retrospective study of the same patients at two different ages [abstract]. Journal of Pediatric Gastroenterology and Nutrition 1988;7(Suppl 1):S40‐5. [CFGD Register: GN141] - PubMed
Araujo 2011 {published data only}
    1. Araujo M, Goyheneix M, Castanos C. High requirement of pancreatic enzyme dose [abstract]. Journal of Cystic Fibrosis 2011;10 Suppl 1:S75, Abstract no: 294. [CFGD Register: GN223]
Beker 1994 {published data only}
    1. Beker LT, Fink RJ, Shamsa FH, Chaney HR, Kluft J, Evans E, et al. Comparison of weight‐based dosages of enteric‐coated microtablet enzyme preparations in patients with cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 1994;19(2):191‐7. [CFGD Register: GN159] - PubMed
Beverley 1987 {published data only}
    1. Beverley DW, Kelleher J, MacDonald A, Littlewood JM, Robinson T. A comparison of four different pancreatic extracts on the absorption of fat in patients with cystic fibrosis [abstract]. 14th Annual Meeting of the European Working Group for Cystic Fibrosis; 1986 Sept 1‐2; Budapest, Hungary. 1986:69. [CFGD Register: GN139a]
    1. Beverley DW, Kelleher J, MacDonald A, Littlewood JM, Robinson T, Walters MP. Comparison of four pancreatic extracts in cystic fibrosis. Archives of Disease in Childhood 1987;62(6):564‐8. [CFGD Register: GN139b] - PMC - PubMed
    1. Littlewood M, Kelleher J, Walters MP, Johnson AW. In vivo and in vitro studies of microsphere pancreatic supplements. Journal of Pediatric Gastroenterology and Nutrition 1988;7(Suppl 1):S22‐9. [CFGD Register: GN139c; MEDLINE: ] - PubMed
Borowitz 2008 {published data only}
    1. Borowitz D, Campion M, Stevens C, Brettman L, Liprotamase 726SG. Reproducibility of coefficient of fat absorption (CFA) in cystic fibrosis patients with pancreatic insufficiency [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S77, Abstract no: 297. [CENTRAL: 848908; CFGD Register: GN211c; CRS: 5500100000010606]
    1. Borowitz D, Falzone RP, Fratazzi C, for the ALTU‐135 Study Group. A phase 3 study of the efficacy and safety of Altu‐135 (Trizytek) for treatment of pancreatic insufficiency in CF [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:423. [CFGD Register: GN211e]
    1. Borowitz D, Stevens C, Brettman LR, Campion M, Chatfield B, Cipolli M, et al. International phase III trial of liprotamase efficacy and safety in pancreatic‐insufficient cystic fibrosis patients. Journal of Cystic Fibrosis 2011;10(6):443‐52. [CENTRAL: 972216; CFGD Register: GN211d; CRS: 5500050000000062; PUBMED: 21831726] - PubMed
    1. Borowitz D, Stevens C, Brettman LR, Campion M, Wilschanski M, Thompson H. Liprotamase long‐term safety and support of nutritional status in pancreatic‐insufficient cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2012;54(2):248‐57. [CENTRAL: 901255; CFGD Register: GN211f; CRS: 5500050000000424; EMBASE: 2012058171] - PubMed
    1. Borowitz D, Stevens C, Campion M, Brettman L. Relationship of baseline & treatment coefficient of fat absorption to growth in patients with cystic fibrosis [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:424, Abstract no: 564. [CENTRAL: 795565; CFGD Register: GN211b; CRS: 5500100000003595]
Bouquet 1988 {published data only}
    1. Bouquet J, Sinaasappel M, Neijens HJ. Malabsorption in cystic fibrosis: mechanisms and treatment. Journal of Pediatric Gastroenterology and Nutrition 1988;7(Suppl 1):S30‐S35. [CFGD Register: GN142] - PubMed
Bowler 1993 {published data only}
    1. Bowler IM, Wolfe SP, Owens HM, Sheldon TA, Littlewood JM, Walters MP. A double blind lipase for lipase comparison of a high lipase and standard pancreatic enzyme preparation in cystic fibrosis. Archives of Disease in Childhood 1993;68(2):227‐30. [CFGD Register: GN155b] - PMC - PubMed
    1. Littlewood JM, Bowler IM, Wolfe SP, Owens HM. A double‐blind comparison of a high lipase and standard pancreatic extract [abstract]. Pediatric Pulmonology 1992;14 Suppl S8:267. [CFGD Register: GN155a]
Brady 1991 {published data only}
    1. Brady MS, Rickard K, Yu PL, Eigen H. Effectiveness and safety of small vs. large doses of enteric coated pancreatic enzymes in reducing steatorrhea in children with cystic fibrosis: a prospective randomized study. Pediatric Pulmonology 1991;10(2):79‐85. [CFGD Register: GN150] - PubMed
Brady 1992 {published data only}
    1. Brady MS, Rickard K, Yu PL, Eigen H. Effectiveness of enteric coated pancreatic enzymes given before meals in reducing steatorrhea in children with cystic fibrosis. Comment in: Journal of the American Dietetic Association 1993 Jan;93(1):14. Journal of the American Dietetic Association 1992;92(7):813‐7. [CFGD Register: GN153] - PubMed
Brady 2006 {published data only}
    1. Brady MS, Garson JL, Krug SK, Kaul A, Rickard KA, Caffrey HH, et al. An enteric‐coated high‐buffered pancrelipase reduces steatorrhea in patients with cystic fibrosis: a prospective, randomized study. Journal of the American Dietetic Association 2006;106(8):1181‐6. [CFGD Register: GN205] - PubMed
    1. Brady MS, Stevens J, Rickard K, Fineberg N. Effectiveness of a new enteric coated (EC) pancreatic enzyme with bicarbonate (pancrecarb®) in reducing steatorrhea in patients with cystic fibrosis (CF): a prospective randomized study [abstract]. Pediatric Pulmonology 1998;26(Suppl 17):354‐5. [CFGD Register: GN187]
Breuel 1996 {published data only}
    1. Breuel K, Wutzke KD, Radke M, Gurk S. Evaluation of pancreatic enzyme activity in cystic fibrosis (CF) by use of a 13C‐Breath test: A comparison of different galemic preparations [abstract]. Israel Journal of Medical Sciences 1996;32(Suppl):S175. [CFGD Register: GN145]
Butt 2001 {published data only}
    1. Butt AM, Kelly E, Pike J, Myilvanasuntharam M, Sequeira K, Morson N, et al. Comparison of the dynamics of lipid assimilation using 13CO2 breath tests with both long‐ and medium‐chain 13C‐labeled stable isotope lipid substrates [abstract]. Pediatric Pulmonology 2001;32(Suppl 22):342. [CFGD Register: GN195]
Chazalette 1988 {published data only}
    1. Chazalette JP, Dain MP, Castaigne JP. Efficacy of pancrease: crossover comparative study versus eurobiol in cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 1988;7(Suppl 1):S46‐8. [CFGD Register: GN183; MEDLINE: ] - PubMed
Chazalette 1993 {published data only}
    1. Chazalette JP. A double‐blind placebo‐controlled trial of a pancreatic enzyme formulation (Panzytrat (R) 25 000) in the treatment of impaired lipid digestion in patients with cystic fibrosis. Drug Investigation 1993;5(5):274‐80. [CFGD Register: GN184]
Colombo 2001 {published data only}
    1. Colombo C, Giunta A, Moretti E, Corbetta C, Valmarana L, Moretto E, et al. Comparison of two stable isotope breath tests (BT) and faecal elastase to assess exocrine pancreatic status in cystic fibrosis (CF) [abstract]. Pediatric Pulmonology 2001;32 Suppl 22:339. [CFGD Register: GN194; MEDLINE: ]
De Boeck 1998 {published data only}
    1. Boeck K, Delbeke I, Eggermont E, Veereman Wauters G, Ghoos Y. Lipid digestion in cystic fibrosis: comparison of conventional and high‐lipase enzyme therapy using the mixed‐triglyceride breath test. Journal of Pediatric Gastroenterology and Nutrition 1998;26(4):408‐11. [CFGD Register: GN185] - PubMed
Desager 2006 {published data only}
    1. Desager KN, Mulberg AE, Verkade H, Malfroot A, Veereman G, Bodewes F, et al. A phase 2, randomized, investigator‐blinded, parallel‐group, pilot study evaluating the safety, palatability and efficacy of four doses of pancrelipase microtablets in the treatment of infants and toddlers with cystic fibrosis‐related pancreatic insufficiency and fat malabsorption [abstract]. Pediatric Pulmonology 2006;41 Suppl 29:377. [CFGD Register: GN206]
Duhamel 1988 {published data only}
    1. Duhamel JF, Vidailhet M, Luyer B, Douchain F, Jehanne M, Clavel R, et al. Multicenter comparative study of a new formulation of pancreatin in gastro‐resistant microgranules for the treatment of exocrine pancreatic insufficiency in children with mucoviscidosis [Etude multicentrique comparative d'une nouvelle presentation de pancreatine en microgranules gastroresistants dans l'insuffisance pancreatique exocrine de la mucoviscidose chez l'enfant.]. Annales de Pediatrie 1988;35(1):69‐74. [CFGD Register: GN143] - PubMed
Duhamel 1998 {published data only}
    1. Duhamel JF, Lenoir G, Druon D, Grimfeld A, Vidailhet M, Chazalette JP, et al. Open‐label, multicentre, cross‐over study to investigate the patients' preference for Creon 10 000 MinimicrospheresTM or Creon in patients with pancreatic exocrine insufficiency due to cystic fibrosis [abstract]. Proceedings of 22nd European Cystic Fibrosis Conference; 1998 June 13‐19; Berlin, Germany. 1998:96. [CFGD Register: GN181]
Durie 1980 {published data only}
    1. Durie PR, Bell L, Linton W, Corey ML, Crozier DN, Forstner GG. The effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis [abstract]. Proceedings of 20th Annual Meeting Cystic Fibrosis Club Abstracts; 1979 May 1; Atlanta, Georgia. 1979:37. [CFGD Register: GN134b]
    1. Durie PR, Bell L, Linton W, Corey ML, Forstner GG. Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis. Gut 1980;21(9):778‐86. [CFGD Register: GN134a] - PMC - PubMed
Dutta 1988 {published data only}
    1. Dutta SK, Hubbard VS, Appler M. Critical examination of therapeutic efficacy of a pH‐sensitive enteric‐coated pancreatic enzyme preparation in treatment of exocrine pancreatic insufficiency secondary to cystic fibrosis. Digestive Diseases and Sciences 1988;33:1237‐44. [CFGD Register: GN183; MEDLINE: ] - PubMed
Easley 1998 {published data only}
    1. Easley D, Krebs N, Jefferson M, Miller L, Erskine J, Accurso F, et al. Effect of pancreatic enzymes on zinc absorption in cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 1998;26(2):136‐9. [CFGD Register: GN180] - PubMed
Ellis 1994 {published data only}
    1. Ellis L, Durie P, Corey M, Davis L, Kalnin D. Changing the coating of pancreatic enzyme microspheres to dissolve at a lower PH does not improve efficacy [abstract]. Pediatric Pulmonology 1994;18 Suppl 10:338. [CFGD Register: GN169]
Foucaud 1989 {published data only}
    1. Foucaud P, Saint‐Marc Girardin MF, Jehanne M, Loeuille G, Gilly R, Lenoir G, et al. Compared efficacity of two pancreatic extracts: eurobiol 25.000 U and eurobiol in children with mucovisidosis [abstract] [Efficacite comparee de deux extraits pancreatiques: eurobiol 25.000 U et eurobiol chez des enfants atteints de mucoviscidose.]. Gastroenterologie Clinique et Biologique 1989;13:A34. [CFGD Register: GN196]
Gan 1994 {published data only}
    1. Gan KH, Heijerman HGM, Geus W, Bakker W, Lamers C. Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in adult cystic fibrosis patients. Alimentary Pharmacology & Therapeutics 1994;8(6):603‐7. [CFGD Register: GN158b] - PubMed
    1. Gan KH, Heijerman HGM, Lamers CBHW, Bakker W. Comparison of a high lipase pancreatic enzyme extract with a regular pancreatin preparation in pancreatic insufficient CF patients [abstract]. Pediatric Pulmonology 1994;18 Suppl 10:340. [CFGD Register: GN158a]
Goodchild 1974 {published data only}
    1. Goodchild MC, Sagaro E, Brown GA, Cruchley PM, Jukes HR, Anderson CM. Comparative trial of pancrex V forte and nutrizym in treatment of malabsorption in cystic fibrosis. British Medical Journal 1974;3(5933):712‐4. [CFGD Register: GN133] - PMC - PubMed
Gow 1981 {published data only}
    1. Gow R, Bradbear R, Francis P, Shepherd R. Comparative study of varying regimens to improve steatorrhoea and creatorrhoea in cystic fibrosis: Effectiveness of an enteric‐coated preparation with and without antacids and cimetidine. Lancet 1981;2(8255):1071‐4. [CFGD Register: GN135a] - PubMed
    1. Shepherd RW, Gow R. Comparative trial of measures to prevent acid‐peptic inactivation of pancreatic enzyme supplements in pancreatic insufficiency due to cystic fibrosis. [abstract]. Australian and New Zealand Journal of Medicine 1982;12:106. [CFGD Register: GN134b]
Graff 2010 {published data only}
    1. Boydd D, Caras SD, Zipfel L, Sander‐Struckmeier S. Evaluation of sparse stool collections compared to 72‐hour collections as an efficacy measure of pancreatic enzyme therapy in patients with exocrine pancreatic insufficiency [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:420, Abstract no: 554. [CENTRAL: 793676; CFGD Register: GN218b; CRS: 5500100000003566]
    1. Caras S, Boyd D, Zipfel L, Sander‐Struckmeier S. Evaluation of stool collections to measure efficacy of PERT in subjects with exocrine pancreatic insufficiency. Journal of Pediatric Gastroenterology and Nutrition 2011;53(6):634‐40. [CENTRAL: 892801; CFGD Register: GN218d; CRS: 5500050000000061; EMBASE: 2011653202] - PubMed
    1. Graff GR, Maguiness K, McNamara J, Morton R, Boyd D, Beckmann K, et al. Efficacy and tolerability of a new formulation of pancrelipase delayed‐release capsules in children aged 7 to 11 years with exocrine pancreatic insufficiency and cystic fibrosis: a multicenter, randomized, double‐blind, placebo‐controlled, two‐period crossover, superiority study. Clinical Therapeutics 2010;32(1):89‐103. [CENTRAL: 743659; CFGD Register: GN218a; CRS: 5500100000003422; PUBMED: 20171415] - PubMed
    1. Maguiness KM, Graff G, Boyd D, Caras D. Efficacy of pancrealipase delayed‐release capsules (CREON®) in correcting nitrogen malabsorption in subjects with CF in randomized, controlled trials [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:417, Abstract no: 547. [CENTRAL: 793539; CFGD Register: GN218c // GN214c; CRS: 5500100000003561]
Heubi 2007 {published data only}
    1. Heubi J, Boas SR, Blake K, Nasr SZ, Woo MS, Graff GR, et al. EUR‐1008, a PEP, is safe and effective in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (EPI) [abstract]. Pediatric Pulmonology 2007;42 Suppl 30:392. [CFGD Register: GN207b]
    1. Heubi JE. The efficacy of EUR‐1008, a novel pancreatic enzyme product (PEP), in the absence of concurrent agents affecting gastric pH, in patients with exocrine pancreatic insufficiency (EPI) [abstract]. American Journal of Respiratory and Critical Care Medicine 2009;179:A1187. [CFGD Register: GN207d]
    1. Heubi JE, Boas SR, Blake K, Nasr SZ, Woo MS, Graff GR, et al. EUR‐1008 (a new pancreatic enzyme product, PEP) was shown to be safe and effective in cystic fibrosis (CF) patients with exocrine pancreatic insufficiency (EPI) [abstract]. Journal of Cystic Fibrosis 2007;6 Suppl 1:S61. [CFGD Register: GN207a]
    1. Heubi JE, Straforini C, Thieroff‐Ekerdt R. Switching CF patients from previous pancreatic enzyme replacement therapy to ZENPEP™ (pancrelipase delayed‐release capsules) improves symptom control of exocrine pancreatic insufficieny [abstract]. Journal of Cystic Fibrosis 2010;9 Suppl 1:S77, Abstract no: 299. [CFGD Register: GN207g]
    1. Wooldridge J, Straforini C, Broussard D, Thieroff‐Ekerdt R. Switching CF patients from previous pancreatic enzyme products to EUR‐1008 (ZENPEP® [pancrelipase] delayed‐release capsules) improves symptom control of EPI in the absence of proton pump inhibitors or H2 receptor agonists [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:422, Abstract no: 559. [CFGD Register: GN207f]
Heubi 2016 {published data only}
    1. Heubi JE, Schaeffer D, Ahrens R, Sollo N, Strausbaugh S, Graff G, et al. Safety and efficacy of a novel microbial lipase (NM‐BL) in patients with exocrine pancreatic insufficiency due to cystic fibrosis [abstract]. Pediatric Pulmonology 2015;50 Suppl 41:402, Abstract no: 555. [CENTRAL: 1092206; CFGD Register: GN252a; CRS: 5500135000001395]
    1. Heubi JE, Schaeffer D, Ahrens RC, Sollo N, Strausbaugh S, Graff G, et al. A randomized, controlled clinical trial of a liquid microbial lipase (NM‐BL) in patients with exocrine pancreatic insufficiency due to cystic fibrosis [abstract]. Journal of Cystic Fibrosis 2016;15 Suppl 1:S29, Abstract no: WS17.6. [CENTRAL: 1157595; CFGD Register: GN252b; CRS: 5500135000001561] - PubMed
    1. Heubi JE, Schaeffer D, Ahrens RC, Sollo N, Strausbaugh S, Graff G, et al. Safety and Efficacy of a Novel Microbial Lipase in Patients with Exocrine Pancreatic Insufficiency due to Cystic Fibrosis: A Randomized Controlled Clinical Trial. Journal of Pediatrics 2016 Jun 10 [Epub ahead of print]:pii: S0022‐3476(16)30257‐8. [CENTRAL: 1157596; CFGD Register: GN252c; CRS: 5500135000001562; DOI: 10.1016/j.jpeds.2016.05.049; PUBMED: 27297209] - DOI - PubMed
Hill 1993 {published data only}
    1. Hill CM, Rolles CJ, Keegan P, Chand RA. Pancreatic enzyme supplementation in cystic fibrosis [letter]. Archives of Disease in Childhood 1993;68(1):150. [CFGD Register: GN171; MEDLINE: ] - PMC - PubMed
Hilman 1982 {published data only}
    1. Hilman B, LeBlanc M, Hawley S, Dufton‐Gross N, Gines D, Tolman N, et al. Cross‐over bioequivalence study of two pH sensitive enteric coated pancreatic enzymes in patients with cystic fibrosis [abstract]. 23rd Annual Meeting Cystic Fibrosis Club Abstracts; 1982 May 14; Washington D.C. 1982:122. [CFGD Register: GN174]
Holsclaw 1979 {published data only}
    1. Holsclaw DS, Fahl JC, Keith HH. Enhancement of enzyme replacement therapy in cystic fibrosis (CF) [abstract]. Proceedings of 20th Annual Meeting Cystic Fibrosis Club Abstracts; 1979 May 1; Atlanta, Georgia. 1979:19. [CFGD Register: GN177]
Hubbard 1984 {published data only}
    1. Hubbard VS, Wolf RO, Lester LA, Egge AC. Diagnostic and therapeutic applications of bentiromide screening test for exocrine pancreatic insufficiency in patients with cystic fibrosis. Comparison with other tests of exocrine pancreatic disease. Digestive Diseases and Sciences 1984;29(10):881‐9. [CFGD Register: GN198] - PubMed
Kalnins 2005 {published data only}
    1. Kalnins D, Corey M, Ellis L, Durie PR, Pencharz PB. Combining unprotected pancreatic enzymes with pH‐sensitive enteric‐coated microspheres does not improve nutrient digestion in patients with cystic fibrosis. Journal of Pediatrics 2005;146(4):489‐93. [CFGD Register: GN202] - PubMed
Kalnins 2006 {published data only}
    1. Kalnins D, Ellis L, Corey M, Pencharz PB, Stewart C, Tullis E, et al. Enteric‐coated pancreatic enzyme with bicarbonate is equal to standard enteric‐coated enzyme in treating malabsorption in cystic fibrosis. Journal of Pediatric Gastroenterology and Nutrition 2006;42(3):256‐61. [CFGD Register: GN188b] - PubMed
    1. Kalnins D, Stewart C, Ellis L, Corey M, Tullis E, Pencharz PB, et al. Does the addition of bicarbonate to an enzyme microsphere preparation improve efficacy? [abstract]. Pediatric Pulmonology 1998;26(Suppl 17):355. [CFGD Register: GN188a; MEDLINE: ]
Katona 2000 {published data only}
    1. Katona DR, Nakamura CT, Bowman CM, Margetis M, Keens TG, Woo MS. Does pancreacarb improve the treatment of pancreatic insufficiency in cystic fibrosis [abstract]. American Journal of Respiratory and Critical Care Medicine 2000;161(3):A72. [CFGD Register: GN197; MEDLINE: ]
Khaw 1977 {published data only}
    1. Khaw KT, Adeniyi‐Jones S, Gordon D, Palombo J, Coryer R, Schlaman C, et al. Comparative effectiveness of viokase, cotazym and pancrease in children with cystic fibrosis [abstract]. 18th Cystic Fibrosis Club Abstracts; 1977. 1977:57. [CFGD Register: GN160]
Konstan 2004 {published data only}
    1. Konstan M, Stern R, Trout R, Sherman J, Eigen H, Wagener J, et al. Ultrase MT12® and Ultrase MT20® in the treatment of exocrine pancreatic insufficiency in cystic fibrosis: safety and efficacy [abstract]. Pediatric Pulmonology 2004;38(Suppl 27):339. [CENTRAL: 797027; CFGD Register: GN201a; CRS: 5500100000003612] - PubMed
    1. Konstan MW, Stern RC, Trout JR, Sherman JM, Eigen H, Wagener JS, et al. Ultrase MT12 and Ultrase MT20 in the treatment of exocrine pancreatic insufficiency in cystic fibrosis: safety and efficacy. Alimentary Pharmacology & Therapeutics 2004;20(11‐12):1365‐71. [CENTRAL: 514057; CFGD Register: GN201b; CRS: 5500050000000064; PUBMED: 15606399] - PubMed
Konstan 2008 {published data only}
    1. Konstan MW, Accurso FJ, Nasr SZ, Ahrens RC, Graff GR. Efficacy and safety of a unique enteric‐coated bicarbonate‐buffered pancreatic enzyme replacement therapy in children and adults with cystic fibrosis. Clinical Investigation 2013;3(8):723‐9. [CENTRAL: 918902; CFGD Register: GN209b; CRS: 5500050000000053; EMBASE: 2013513339] - PMC - PubMed
    1. Konstan MW, Strausbaugh SD, Ahrens RC, Accurso FJ, Graff GR, Nasr SZ. A randomized, double‐blind, placebo‐controlled, multicenter, cross‐over study to evaluate the effectiveness and safety of a novel pancrelipase (Pancrecarb® MS‐16) in reducing steatorrhea in children and adults with cystic fibrosis [abstract]. Pediatric Pulmonology 2008;43 Suppl 31:425. [CFGD Register: GN209a]
Konstan 2010 {published data only}
    1. Konstan MW, Liou TG, Strausbaugh SD, Ahrens R, Kanga JF, Graff GR, et al. Efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in the treatment of malabsorption in exocrine pancreatic insufficiency in cystic fibrosis. Gastroenterology Research and Practice. United States: Hindawi Publishing Corporation (410 Park Avenue, 15th Floor, 287 pmb, New York NY 10022, United States), 2010. [CENTRAL: 889209; CFGD Register: GN239; CRS: 5500050000000060; EMBASE: 2011059347] - PMC - PubMed
Kraisinger 1993 {published data only}
    1. Kraisinger M, Hendeles L, Stecenko A, Neiberger R. Hyperuricosuria associated with microencapsulated pancreated enzymes [abstract]. Pediatric Pulmonology 1993;16 Suppl 9:269. [CFGD Register: GN166]
Kuo 2011 {published data only}
    1. Kuo P, Stevens JE, Russo A, Maddox A, Wishart JM, Jones KL, et al. Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis‐‐effects of pancreatic enzyme supplementation. Journal of Clinical Endocrinolgy and Metabolism 2011;96(5):E851‐5. [CFGD Register: GN224] - PubMed
Lancellotti 1996 {published data only}
    1. Lancellotti L, Cabrini G, Zanolla L, Mastella G. High‐ versus low‐lipase acid‐resistant enzyme preparations in cystic fibrosis: a crossover randomized clinical trial. Journal of Pediatric Gastroenterology and Nutrition 1996;22(1):73‐8. [CFGD Register: GN172; MEDLINE: ] - PubMed
Lazaro 1990 {published data only}
    1. Lazaro A, Olivan G, Ros MI, Nebreda JR, Bueno M. Comparative trial between two pancreatine in enteric coated microspheres preparations in children with cystic fibrosis and steatorrhoea [Estudio comparativo cruzado de dos preparados de pancreatina en microesferas en una serie de ni±os con fibrosis quÝstica y esteatorrea.]. BoletÝn de la Sociedad de PediatrÝa de Arag¾n, La Rioja y Soria 1990;20:170‐6. [CFGD Register: GN193]
Leitz 2009 {published data only}
    1. Leitz GJ, Trapnell B, Strausbaugh S, Woo M, Shin‐Yir T, Silber S, et al. A randomised double‐blind (withdrawal) phase 3 study to evaluate the efficacy and tolerability of pancrease‐mt capsules compared with placebo in the treatment of subjects with cystic fibrosis‐dependent exocrine pancreatic insufficiency [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:407, Abstract no: 544. [CFGD Register: GN213a]
    1. Trapnell BC, Strausbaugh SD, Woo MS, Tong S‐Y, Silber SA, Mulberg AE, et al. Efficacy and safety of PANCREAZE for treatment of exocrine pancreatic insufficiency due to cystic fibrosis. Journal of Cystic Fibrosis 2011;10(5):350‐6. [CENTRAL: 887395; CFGD Register: GN213b ; CRS: 5500050000000059; EMBASE: 2011499244] - PubMed
Lubin 1979 {published data only}
    1. Lubin AH, Scott DH, Bonner JL. Failure of antacids to improve the effectiveness and/or utilization of pancreatic extracts in children with cystic fibrosis [abstract]. Proceedings of 20th Annual Meeting Cystic Fibrosis Club Abstracts; 1979 May 1; Atlanta, Georgia. 1979:57. [CFGD Register: GN190]
Mack 1991 {published data only}
    1. Mack G, Cooper PJ, Buchanan N. Effects of enzyme supplementation on oral absorption of ciprofloxacin in patients with cystic fibrosis. Antimicrobial Agents and Chemotherapy 1991;35:1484‐5. [CFGD Register: PI135] - PMC - PubMed
Mischler 1980 {published data only}
    1. Mischler EH, Parrel SJ, Odell GB, Farrell PM. A controlled study of enteric coated pancreatic enzyme microspheres in patients with cystic fibrosis [abstract]. 21st Annual Meeting Cystic Fibrosis Club Abstracts; 1980 April 29; San Antonio, Texas. 1980:80. [CFGD Register: GN161]
Mischler 1982 {published data only}
    1. Mischler EH, Parrell S, Farrell PM, Odell GB. Comparison of effectiveness of pancreatic enzyme preparations in cystic fibrosis. American Journal of Diseases of Children 1982;136(12):1060‐3. [CFGD Register: GN136] - PubMed
Morrison 1992 {published data only}
    1. Morrison G, Morrison J, Redmond A, Byers C, McCracken K, Dodge JA. Pancreatic enzyme supplements in cystic fibrosis [letter]. Lancet 1991;338:1596‐7. [CFGD Register: GN154b; MEDLINE: ] - PubMed
    1. Morrison G, Morrison JM, Redmond AO, Byers CA, McCracken KJ, Dodge JA, et al. Comparison between a standard pancreatic supplement and a high enzyme preparation in cystic fibrosis. Alimentary Pharmacology & Therapeutics 1992;6(5):549‐55. [CFGD Register: GN154a] - PubMed
Munck 2009 {published data only}
    1. Munck A. Creon® for children is preferred by parents of CF patients to Creon® 10000 MMS [abstract]. Journal of Cystic Fibrosis 2006;5 Suppl 1:S57. [CFGD Register: GN204a]
    1. Munck A, Duhamel JF, Lamireau T, Luyer B, Tallec C, Bellon G, et al. Pancreatic enzyme replacement therapy for young cystic fibrosis patients. Journal of Cystic Fibrosis 2009;8(1):14‐8. [CFGD Register: GN204b] - PubMed
Munoz 1987 {published data only}
    1. Munoz Conde J, Perez Perez M, Dapena Fernandes J. Cross‐over comparison of creonR and pankreon granulateR in cystic fibrosis with steatorrhoea: [abstract]. 15th Annual Meeting of the European Working Group for Cystic Fibrosis; 1987; Oslo, Norway. 1987. [CFGD Register: GN163]
NCT02137382 {unpublished data only}
    1. NCT02137382. A double‐blind, randomized, multicenter, cross‐over study to compare the effect of Creon N and Creon® on fat digestion in subjects ≥ 12 years of age with pancreatic exocrine insufficiency due to cystic fibrosis. clinicaltrials.gov/ct2/show/NCT02137382 (first received 12 February 2014).
Neijens 1982 {published data only}
    1. Neijens HJ, Bouquet J, Sinaasappel M, Kerrebijn KF, Grose WFA. Comparison of the effects of pancreatic enzyme as acid‐resistant microspheres to granules and of the addition of N‐acetyl‐cysteine on the malabsorption in CF [abstract]. 11th European Cystic Fibrosis Conference; 1982; Brussels. 1982:197. [CFGD Register: GN179]
Ritz 2004 {published data only}
    1. Ritz MA, Fraser RJ, Matteo AC, Greville H, Butler R, Cmielewski P, et al. Evaluation of the 13C‐triolein breath test for fat malabsorption in adult patients with cystic fibrosis. Journal of Gastroenterology and Hepatology 2004;19(4):448‐53. [CFGD Register: GN200] - PubMed
Robinson 1989 {published data only}
    1. Robinson PJ, Olinsky A. Evaluation of a new enteric coated pancreatic enzyme [abstract]. Excerpta Medica, Asia Pacific Congress Series 1988;74:G.I.(b)6. [CFGD Register: GN147a]
    1. Robinson PJ, Olinsky A, Smith AL, Chitravanshi SB. High compared with standard dose lipase pancreatic supplement. Archives of Disease in Childhood 1989;64(1):143‐5. [CFGD Register: GN147b] - PMC - PubMed
Robinson 1998 {published data only}
    1. Robinson PJ, Natoli G. Comparison of high‐dose and standard‐dose pancreatic enzyme capsules in children with cystic fibrosis. Australian Journal of Hospital Pharmacy 1998;28(3):160‐4. [CFGD Register: GN191]
Santini 2000 {published data only}
    1. Santini B, Antonelli M, Battistini A, Bertasi S, Collura M, Esposito I, et al. Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis. Digestive Liver Disease 2000;32(5):406‐11. [CFGD Register: GN178b] - PubMed
    1. Santini B, Bertasi S, Collura M, Febbaro L, Ferrari R, Ferrero L, et al. Open label multicenter cross over study on two enteric coated microspheres in the treatment of CF pancreatic insufficiency [abstract]. 21st European Cystic Fibrosis Conference; 1997 June 1‐6; Davos, Switzerland. 1997:170. [CFGD Register: GN178a]
Shah 1993 {published data only}
    1. Shah A, Dinwiddie R, Madge S, Prescott P, Hudson G. High dose Nutrizym 22 in cystic fibrosis. European Journal of Pediatrics 1993;152(9):763‐4. [CFGD Register: GN156b] - PubMed
    1. Shah A, Hudson G, Madge S, Dinwiddie R. High dose Nutrizym 22 in cystic fibrosis [abstract]. Proceedings of 11th International Cystic Fibrosis Congress; 1992; Dublin, Ireland. 1992:TP78. [CFGD Register: GN156a]
Sinaasappel 1998 {published data only}
    1. Sinaasappel M, Swart GR, Hoekstra JH, Houwen RH, Laag J, Gijsbers CF, et al. Double‐blind, cross‐over, study to prove the equivalence of creon 10000 minimicrospheres (MMS) versus creon 8000 microspheres (MS) in patients with cystic fibrosis (CF) [abstract]. Pediatric Pulmonology 1998;26 Suppl 17:358. [CFGD Register: GN186]
Stapleton 2001 {published data only}
    1. Stapleton DR, Gurrin LC, Zubrick SR, Silburn SR, Sherriff JL, Sly PD. The effect of 'Go and Grow with CF' on nutrition and pancreatic enzyme knowledge of children with cystic fibrosis. Australian Journal of Nutrition and Dietetics 2001;58(3):164‐8. [CFGD Register: GN199]
Stern 2000 {published data only}
    1. Stern RC, Eisenberg JD, Wagener JS, Ahrens R, Rock M, doPico G, et al. A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency. American Journal of Gastroenterology 2000;95(8):1932‐8. [CFGD Register: GN192] - PubMed
Thomson 1993 {published data only}
    1. Thomson M, Clague A, Cleghorn GJ, Shepherd RW. Comparative in vitro and in vivo studies of enteric‐coated pancrelipase preparations for pancreatic insufficiency. Journal of Pediatric Gastroenterology and Nutrition 1993;17(4):407‐13. [CFGD Register: GN157] - PubMed
Trapnell 2009 {published data only}
    1. Maguiness K, Graff G, Boyd D, Caras S, Beckmann K. Efficacy of Pacrealipase delayed‐release capsules (CREON®) in correcting nitrogen malabsorption in subjects with CF in randomized controlled trials [abstract]. Pediatric Pulmonology 2010;45 Suppl 33:417, Abstract no: 547. [CFGD Register: GN214c // GN218c]
    1. Trapnell B, Maguiness K, Graff G, Boyd D, Caras S, Beckmann K. Pancrelipase delayed‐release capsules (Creon®) in patients with pancreatic insufficiency due to CF: age and severity analyses [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:402, Abstract no: 531. [CFGD Register: GN214]
    1. Trapnell BC, Maguiness K, Graff G, Boyd D, Beckmann K, Caras S. Efficacy and safety of Creon® 24,000 in subjects with exocrine pancreatic insufficiency due to cystic fibrosis. Journal of Cystic Fibrosis 2009;8(6):370‐7. [CFGD Register: GN214d] - PubMed
    1. Trapnell BC, Maguiness K, Graff GR, Boyd D, Caras SD. Efficacy and safety of a new formulation of CREON® in patients with exocrine pancreatic insufficiency due to CF [abstract]. Journal of Cystic Fibrosis 2009;8 Suppl 2:S80, Abstract no: 323. [CFGD Register: GN214b] - PubMed
van der Haak 2016 {published data only}
    1. Haak N, Boase J, Davidson G, Butler R, Miller M, Kaambwa B, et al. Preliminary report of the 13C‐mixed triglyceride breath test to assess timing of pancreatic enzyme replacement therapy in children with cystic fibrosis. Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society 2016 Apr 19 [Epub ahead of print]:pii: S1569‐1993(16)30017‐0. [CENTRAL: 1157597; CFGD Register: GN258; CRS: 5500135000001563; DOI: 10.1016/j.jcf.2016.03.008; PUBMED: 27102891] - DOI - PubMed
Van de Vijver 2011 {published data only}
    1. Vijver E, Desager K, Mulberg AE, Staelens S, Verkade HJ, Bodewes FA, et al. Treatment of infants and toddlers with cystic fibrosis‐related pancreatic insufficiency and fat malabsorption with pancrelipase MT. Journal of Pediatric Gastroenterology and Nutrition 2011;53(1):61‐4. [CENTRAL: 799167; CFGD Register: GN240; CRS: 5500050000000065; PUBMED: 21694537] - PubMed
Vitti 1975 {published data only}
    1. Vitti TG, Berg TJ, Pagtakhan RD. The effect of pancreatic enzyme supplement on the intestinal absorption of ampicillin and cloxacillin in children with cystic fibrosis [abstract]. Proceedings of 16th Cystic Fibrosis Club Abstracts; 1975. 1975:56. [CFGD Register: PI81]
Warwick 1982 {published data only}
    1. Warwick WJ, Budd JR. Comparison of cotayme‐S and pancrease [abstract]. 23rd Annual Meeting Cystic Fibrosis Club Abstracts; 1982 May 14; Washington D.C.. 1982:145. [CFGD Register: GN175]
Weber 1979 {published data only}
    1. Weber AM, Gheldere B, Roy CC, Fontaine A, Dufour OL, Morin CL, et al. Effectiveness of enteric coated pancrease in cystic fibrosis (CF) children under 4 years old [abstract]. 20th Annual Meeting Cystic Fibrosis Club Abstracts; 1979 May 1; Atlanta, Georgia. 1979:18. [CFGD Register: GN176]
Wooldridge 2009 {published data only}
    1. Wooldridge JL, Heubi JE, Amaro‐Galvez R, Boas SR, Blake KV, Nasr SZ, et al. EUR‐1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. Journal of Cystic Fibrosis 2009;8(6):405‐17. [CFGD Register: GN212b] - PubMed
    1. Wooldridge JL, Heubi JE, Thieroff‐Ekerdt R. Exploratory analysis of the effect of dosing options on the efficacy of EUR‐1008 (Zenpep) in young children with CF and exocrine pancreatic insufficiency [abstract]. Pediatric Pulmonology 2009;44 Suppl 32:411, Abstract no: 554. [CFGD Register: GN212a]
    1. Wooldridge JL, Schaeffer D, Jacobs D, Thieroff‐Ekerdt R. Long‐term safety assessment of Zenpep® (pancrelipase delayed‐release capsules) in infants aged 1‐12 months with exocrine pancreatic insufficiency associated with cystic fibrosis [abstract]. Pediatric Pulmonology 2012;47(S35):418, Abstract no: 531. [CFGD Register: GN225]
Zentler 1992 {published data only}
    1. Assoufi BA, Zentler‐Munro P, Cornell S, Northfield TC, Hodson ME. Efficacy of acid resistant fungal lipase in the treatment of steatorrhoea due to adult cystic fibrosis [abstract]. Pediatric Pulmonology 1988;5(Suppl 2):145. [CFGD Register: GN151a] - PubMed
    1. Zentler Munro PL, Assoufi BA, Balasubramanian K, Cornell S, Benoliel D, Northfield TC, et al. Therapeutic potential and clinical efficacy of acid‐resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis. Pancreas 1992;7(3):311‐9. [CFGD Register: GN151b] - PubMed

References to studies awaiting assessment

Dalzell 1992 {published data only}
    1. Dalzell AM, Heaf DP. High dose pancreatic enzymes in distal intestinal obstruction syndrome [abstract]. Proceedings of Paediatric Research Society Meeting. 1992:148. [CFGD Register: GN170; MEDLINE: ]
Holsclaw 1980 {published data only}
    1. Holsclaw DS, Keith H. Long‐term benefits of pH‐sensitive enteric‐coated enzymes in CF [abstract]. Proceedings of 8th International Cystic Fibrosis Congress; 1980; Toronto, Canada. 1980:19a. [CFGD Register: GN137]
Knill 1973 {published data only}
    1. Knill Jones RP, Pearce H, Batten PJ, Williams R. Comparative double‐blind experience of a polyenzymatic preparation in chronic pancreatic insufficiency (author's transl) [Essai comparatif en double insu d'une preparation polyenzymatique dans l'insuffisance pancreatique chronique.]. Acta Gastroenterologica Belgica 1973;36(9):489‐504. [CFGD Register: GN132] - PubMed
Lenoir 2008 {published data only}
    1. Lenoir G, Dubray C, Hubert D, Chiron R, Philippe P, Sarles J. Phase 2 study in young CF adults with the recombinant acid lipase MERISPASE® [abstract]. Journal of Cystic Fibrosis 2008;7 Suppl 2:S29. [CFGD Register: GN208]
Regele 1996 {published data only}
    1. Regele S, Henker J, Munch R, Barbier Y, Stern M. Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double‐blind trial of pancreatic supplementation. Journal of Pediatric Gastroenterology and Nutrition 1996;22(1):68‐72. [CFGD Register: GN173; MEDLINE: ] - PubMed
Taylor 1993 {published data only}
    1. Taylor CJ, McGaw J, Barraclough M, Ghosal S, Beckles‐Wilson N, Keegan P. Clinical trial of High lipase pancreatic enzyme supplementation in cystic fibrosis (CF) ; Evaluation of Creon 25,000 [abstract]. Pediatric Pulmonology 1993;16 Suppl 9:306. [CFGD Register: GN167]

References to ongoing studies

NCT02279498 {unpublished data only}
    1. NCT02279498. Study of oral liprotamase unit‐matched therapy of non‐porcine origin in patients with cystic fibrosis. clinicaltrials.gov/ct2/show/NCT02279498 (first received 28 October 2014).

Additional references

Baker 2008
    1. Baker SS. Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis. Therapeutics and Clinical Risk Management 2008;4(5):1079‐84. - PMC - PubMed
BNF for Children 2014
    1. BMJ Publishing Group Ltd. BNF for Children. Section 1.9.4: Pancreatin. www.medicinescomplete.com/mc/bnf/current/PHP732‐pancreatin.htm (accessed 25 June 2014).
Corey 1988
    1. Corey M, McLaughlin FJ, Williams M, Levinson H. A comparison of the survival, growth and pulmonary function in patients with cystic fibrosis. Journal of Clinical Epidemiology 1988;41:583‐91. - PubMed
CSM 1995
    1. Committee on safety of medicines (CSM). Report of the pancreatic enzymes working party. London. Committee on the Safety of Medicines: Medicines Control Agency 1995.
Dodge 2006
    1. Dodge JA, Turck D. Cystic fibrosis: nutritional consequences and management. Best practice & research. Clinical Gastroenterology 2006;20(3):531‐46. - PubMed
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JPT, Curtin F, Worthington HV, Vail A. Meta‐analyses involving cross‐over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140‐9. - PubMed
Fieker 2011
    1. Fieker A, Philpott J, Armand M. Enzyme replacement therapy for pancreatic insufficiency: present and future. Clinical and Experimental Gastroenterology 2011;4:55‐73. [DOI: 10.2147/CEG.S17634] - DOI - PMC - PubMed
Greer 1991
    1. Greer R, Shepherd R, Cleghorn G, Bowling FG, Holt T. Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis. Journal of Pediatric Gastroenterology & Nutrition 1991;13(1):52‐8. - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC on behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.
Law 2014
    1. Law V, Knox C, Djoumbou Y, Jewison J, Guo AC, Liu Y, et al. Drugbank 4.0: Shedding new light on drug metabolism. Nucleic Acids Research 2014;42(1):1091‐7. - PMC - PubMed
Leus 2000
    1. Leus J, Biervliet S, Robberecht E. Detection and follow up of exocrine pancreatic insufficiency in cystic fibrosis: a review. European Journal of Pediatrics 2000;159(8):563‐8. - PubMed
Quittner 2009
    1. Quittner AL, Modi AC, Wainwright C, Otto K, Kirihara J, Montgomery AB. Determination of the minimal clinically important difference scores for the Cystic Fibrosis Questionnaire‐Revised respiratory symptom scale in two populations of patients with cystic fibrosis and chronic Pseudomonas aeruginosa airway infection. Chest 2009;135(6):1610‐8. - PMC - PubMed
RevMan 2012 [Computer program]
    1. The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.2. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2012.
Schibli 2002
    1. Schibli S, Durie PR, Tullis ED. Proper usage of pancreatic enzymes. Current Opinion in Pulmonary Medicine 2002;8(6):542‐6. - PubMed
Stallings 2008
    1. Stallings V, Stark L, Robinson K, Feranchak A, Quinton H. Evidence‐based practice recommendations for nutrition‐related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. Journal of the American Dietetic Association 2008;108(5):832‐9. - PubMed
Walkowiak 2005
    1. Walkowiak J, Sands D, Nowakowska A, Piotrowski R, Zybert K, Herzig KH, et al. Early decline of pancreatic function in cystic fibrosis patients with class 1 or 2 CFTR mutations. Journal of Paediatric Gastroenterology & Nutrition 2005;40(2):199‐201. - PubMed
Waters 1990
    1. Waters DL, Dorney SF, Gaskin KJ, Gruca MA, O'Halloran M, Wilcken B. Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. New England Journal of Medicine 1990;322(5):303‐8. - PubMed

References to other published versions of this review

Somaraju 2014
    1. Somaraju UR, Solis‐Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database of Systematic Reviews 2014, Issue 10. [DOI: 10.1002/14651858.CD008227.pub2] - DOI - PubMed

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