Diagnostic criteria and details of trial process
| Study | Criteria for chronic pancreatitis | Criteria for exocrine pancreatic insufficiency before randomisation | Run-in (washout) phase | Treatment phase | Fat in diet/day (g) | Faecal dye | Controlled timing of faecal fat collection | Adverse events |
|---|---|---|---|---|---|---|---|---|
| Graham32 | NR | NR | NR | 6 days for each of the four PERT preparations | 100 | NR | 3-day equilibration followed by 3-day collection | NR |
| Dutta et al 33 | Radiological evidence of pancreatic calcifications or multiple strictures in MPD, or histological evidence | Normal d-xylose absorption; marked abnormal secretin test; FFE >7 g/day on a 100 g/day fat intake | NR | 3 days for each of the two PERT preparations | 100 | NR | 3-day equilibration followed by 3-day collection | NR |
| Lankish et al 34 | Typical disease history and/or histology | Abnormal secretin-pancretozymin test; FFE >15 g/day | 3 days | 5 days for each of the three PERT preparations | 100 | NR | 2-day equilibration followed by 3-day collection | NR |
| Halgreen et al 35 | Imaging indicative of pancreatic calcification, previous acute attacks and/or typical abnormalities by ERCP | Meal stimulated duodenal lipase <50 kU/L and FFE >8 g/day | 14 days | 14 days for PERT or placebo then vice versa | 100 | NR | 2-day equilibration followed by 3-day collection | NR |
| Gouerou et al 36 | Imaging indicative of pancreatic calcification, ERCP abnormalities or other histological signs | FFE >8 g/day | 10 days | 21 days each for either two PERT preparations then vice versa | NR | NR | 3 days before treatment and 3 days at the end of each treatment period | PERT1: 11.4%; PERT2: 11.4% |
| Jørgensen et al 37 | Pancreatic calcifications on US, ERCP, CT and/or anatomy abnormalities in laparotomy | Meal stimulated duodenal enzyme activity below 10% and FFE 15 g/day on free diet | 7 days | 7 days for each of the two PERT preparations | NR | Yes, brilliant blue | 3 days before treatment and after 7 days of each treatment | NR |
| Paris38 | Radiology of preoperative confirmation | FFE >10 g/day | 7–9 days placebo followed by 5 days | 8-day PERT or placebo | >100 | NR | 4-day equilibration followed by 3-day collection | PERT: 10.3%; placebo: 9.1% |
| Delhaye et al 39 | Pancreatic calcifications, typical abnormalities in ERCP, or histology | FFE >10 g/day | NR | 14 days for each of the four PERT preparations followed by 5 days of standard diet period in between | >100 | NR | 14-day equilibration followed by 3- day collection | NR |
| Opekun Jr et al 40 | NR | Documented symptomatic steatorrhoea | 6- day placebo | 6 days for each of the three PERT preparations and a placebo with 2-day washout period in between | 100 | NR | 3-day equilibration followed by 3-day collection | NR |
| Halm et al 41 | US, CT, ERCP or X-ray indicative of pancreatic calcification and <6 acute attacks | FFE >7.5 g/day | 7-day placebo followed by 7-day PERT MS | 14 days of each two PERT MS and MMS with a 7-day washout period in between | 70–80 | NR | 4-day equilibration followed by 3-day collection in placebo period, 11-day equilibration followed by 3-day collection in PERT period | PERT MS: 21.7%; PERT MMS: 17.4% |
| O'Keefe et al 42 | Typical signs of chronic pancreatitis in CT, US, ERCP or pancreatic calcification in X-ray | FFE >10 g/day | 7-day placebo followed by 7-day PERT | 14-day PERT or placebo | ∼100 | NR | 4-day equilibration followed by 3-day collection in placebo period, 11-day equilibration followed by 3-day collection in PERT period | NR |
| Domínguez- Muñoz et al 43 | Severe chronic pancreatitis diagnosed by MRI, CT and/or EUS (Cambridge and Wiersema criteria) | FFE >7 g/day | >5 days | 7 days for each of the three PERT preparations (consecutive) | 92 | NR | 5-day equilibration followed by 3- day collection | NR |
| Vecht et al 44 | Clinical history, alterations of pancreatic morphology in CT, ERCP (Cambridge score) | FFE >10 g/day | 15 days | 15 days each for either high or low dose of PERT preparation then vice versa | NR | NR | 3-day collection | NR |
| Safdi et al 45 | Documented chronic pancreatitis | CFA <80% and/or FFE >10 g/day in run-in phase; study compliance | 14-day placebo | 14-day PERT or placebo | >100 | NR | 11-day equilibration followed by 3-day collection | PERT: 23.1%; placebo: 35.7% |
| Whitcomb et al 46 | Medical history and imaging indicative calcification and/or histology | CFA <80% and/or total faecal fat content ≥10 g/day; study compliance | 5-day placebo | 7-day PERT or placebo | >100 | Yes, indigo carmine | 2-day equilibration followed by 3-day collection in run-in phase, 4-day equilibration followed by 3-day collection in PERT period | PERT: 20.0%; placebo: 20.7% |
| Toskes et al 47 | Medical history and one of the criteria: ERCP Cambridge 4, CT with dilated MPD, atrophy, calcification, US, EUS with more than five criteria; partial or distal pancreatectomy not due to cancer | Faecal elastase ≤100 µg/g | 7–9-day placebo | ∼8 days each for either high or low dose of PERT preparations then vice versa | 100 | Yes, indigo carmine | 4-day equilibration followed by 3-day collection in run-in phase, 6-day equilibration followed by 3-day collection in each PERT period | Low-dose PERT: 39.2%; high-dose PERT: 41.3%; placebo: 42.7% |
| Thorat et al 48 | Imaging indicative calcifications or MPD dilatation and/or histology | CFA ≤80% | 7-day followed by 7-day PERT | 7-day PERT or placebo | 100 | NR | 4-day equilibration followed by 3-day collection | PERT: 35.3%; placebo: 25.0% |
CFA, coefficient of fat absorption; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasonography; FFE, faecal fat absorption; MMS, minimicrospheres; MPD, main pancreatic duct; MS, microspheres; NR, not reported; PERT, pancreatic enzyme replacement therapy; US, ultrasonography.