Methods
Eligibility criteria
Information sources
Search
Study selection
Data collection process
Data items
Risk of bias in individual studies
Publication bias
Certainty in evidence
Summary measures and synthesis of data
Results
Study selection
Study characteristics
Study information | PENGUIN-trial | TENSION-trial | MISER-trial |
---|---|---|---|
First author | O.J. Bakker | S. van Brunschot | J. Y. Bang |
Year published | 2012 | 2018 | 2019 |
Country | Netherlands | Netherlands | United States of America |
Design | RCT, multicentric | RCT, multicentric | RCT, monocentric |
Trial time period | 2008–2010 | 2011–2015 | 2014–2017 |
Primary outcome | Postprocedural serum interleukin 6 levels | Composite outcome of death and major complications | Composite outcome of death and major complications |
Stage of pancreatitis | Infected necrotizing pancreatitis or suspected infected necrotizing pancreatitis | Infected necrotizing pancreatitis or suspected infected necrotizing pancreatitis | Infected necrotizing pancreatitis or suspected infected necrotizing pancreatitis |
Timing of intervention | Intervention was postponed to at least a month after onset of disease whenever possible | Randomization and intervention postponed until 4 weeks after onset of pancreatitis whenever possible | Randomization postponed until better demarcation of necrosis if necessary |
Inclusion criteria | Confirmed or suspected infected necrotizing pancreatitis eligible for both endoscopic or surgical necrosectomy | Confirmed or suspected infected necrotizing pancreatitis eligible for both endoscopic or surgical necrosectomy | Confirmed or suspected infected necrotizing pancreatitis eligible for both endoscopic or surgical necrosectomy |
Exclusion criteria | - Previous surgical or endoscopic necrosectomy - Previous exploratory laparotomy - Pancreatitis as consequence of abdominal surgery - Flare up of chronic pancreatitis - Abdominal compartment syndrome - Perforation of visceral organ - Bleeding as indication for intervention | - Previous invasive interventions for necrotizing pancreatitis - Chronic pancreatitis - Recurrent acute pancreatitis - Indication for emergency laparotomy | - Prior surgical or endoscopic drainage or necrosectomy - Pancreatitis secondary to trauma or surgical intervention - Presence of indwelling percutaneous catheters before randomization - Chronic pancreatitis - Pregnancy |
Patients randomized | 22 | 98 | 70 |
Patients analyzed by trial authors | 20 | 98 | 66 |
Method of analyzing | mITT | ITT | mITT |
Excluded patients | 2 (patients excluded due to clinical improvement after drainage) | 0 | 4 (2 Patients excluded due to clinical improvement after drainage, 2 patients excluded due to protocol violation) |
Data of excluded patients | Confirmation acquired from authors that no further complications or mortality occurred in patients excluded due to clinical improvement | No further data required | Patients excluded due to “resolution of symptoms after percutaneous drainage” included in ITT analysis under the assumption that they showed no further complications. Patients excluded due to protocol violations were not included in analysis |
Endoscopic treatment | Endoscopic drainage and subsequent endoscopic necrosectomy | Endoscopic drainage and if necessary subsequent endoscopic necrosectomy. 2, 7 Fr plastic stents used | Endoscopic drainage and if necessary subsequent endoscopic necrosectomy. 2, 7 Fr plastic stents or metal stents or more than one drainage sites (multi-gateway) |
Surgical treatment | - VARD following previously placed retroperitoneal percutaneous drain OR - Open necrosectomy if VARD not possible | - Percutaneous drainage and if necessary subsequent VARD | - Laparoscopic cystogastrostomy with pancreatic necrosectomy OR - Percutaneous drainage and subsequent VARD |
Quality control | Expert panel of gastrointestinal surgeons, gastroenterologists and radiologists evaluated candidates prior to randomization | Expert panel of gastrointestinal surgeons, gastrointestinal endoscopists and radiologists evaluated candidates prior to randomization | Expert panel of gastrointestinal surgeons, gastroenterologists, and radiologists evaluated candidates prior to randomization |
Funding of study | First author received grant from Netherlands Organization for Health Research and Development to perform clinical trials | Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development | No mention of special trial funding |
Endoscopy (10) | Surgery (12) | Endoscopy (51) | Surgery (47) | Endoscopy (34) | Surgery (34) | |
---|---|---|---|---|---|---|
Only drainage | 0 | 2 | 22 | 24 | 22 | 2 |
Step-up procedure (initial drainage and subsequent necrosectomy) | 9 (one patient received immediate necrosectomy after drainage) | 8 | 26 | 22 | 11 (one patient received immediate necrosectomy after drainage) | 9 |
Direct necrosectomy without previous drainage | 0 | 2 | 0 | 0 | 23 | |
Spontaneous improvement without treatment | 0 | 0 | 1 | 1 | 0 | 0 |
Further/differing treatment OR subsequent conversion to other treatment modality | 6 (2 patients received additional VARD after multiple (5/7) unsuccessful endoscopic necrosectomies, 4 patients received percutaneous catheter drainage before endoscopic treatment) | 16 (2 to surgical step-up after unsuccessful endoscopy, 14 patients received additional percutaneous drainage) | 2 (2 patients received additional endoscopic drainage) | 20 (6 patients received additional percutaneous drainage after initial endoscopic drainage, 14 patients had an indwelling percutaneous catheter at time of intervention) | 6 (One patient underwent open necrosectomy, 2 patients underwent endoscopic necrosectomy after aborted surgical necrosectomy; 3 patients underwent endoscopic necrosectomy (1) or drainage (2) after no clinical improvement after surgery) |
Patient characteristics | PENGUIN-trial | TENSION-trial | MISER-trial | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Endoscopy (10) | Surgery (10) | Endoscopy (51) | Surgery (47) | Endoscopy (34) | Surgery (32) | |||||||
Age in years | 62 (58–70) | 64 (46–72) | 63 (14) | 60 (11) | 55.6 (14.2) | 52.9 (14.2) | ||||||
Men (%) | 60 | 80 | 67 | 62 | 65 | 66 | ||||||
BMI (mean) | 29 (26–35) | 27 (23–37) | 29 (25–32) | 28 (25–30) | Not available | Not available | ||||||
Cause of pancreatitis | ||||||||||||
Biliary cause of pancreatitis (%) | 60 | 70 | 51 | 64 | 41 | 25 | ||||||
Alcohol as cause for pancreatitis (%) | 20 | 20 | 14 | 15 | 18 | 34 | ||||||
Other cause of pancreatitis (%) | 20 | 10 | 35 | 21 | 41 | 41 | ||||||
Severity of illness | ||||||||||||
CT-severity score | 8 (4–10) | 8 (4–10) | 6 (6–8) | 8 (6–10) | 4–6 | 8–10 | 4–6 | 8–10 | ||||
3% | 97% | 9% | 90% | |||||||||
APACHE II score | 10 (6–14) | 11 (7–14) | 9 (5–13) | 10 (6–13) | 30 (26–35) | 21 (16–23) | ||||||
Time since onset until intervention (days) | 48 (36–74) | 59 (29–69) | 39 (28–54) | 41 (28–52) | < 28 | 28–42 | > 42 | < 28 | 28–42 | > 42 | ||
27% | 56% | 18% | 22% | 50% | 28% | |||||||
Infected necrosis (%) | 100 | 90 | 90 | 98 | 91 | 94 | ||||||
Admitted to ICU at randomization (%) | 20 | 30 | 41 | 53 | 71 | 66 | ||||||
Multiple organ failure 24 h prior to randomization (%) | 20 | 10 | 18 | 15 | 21 | 22 | ||||||
SIRS prior to randomization (%) | 90 | 70 | 65 | 81 | 47 | 50 | ||||||
Single organ failure prior to randomization (%) | 20 | 30 | 25 | 30 | 6 | 9 | ||||||
ASA 1 status (%) | 10a | 10a | 33a | 38a | 0b | 0b | ||||||
ASA 2 status (%) | 90a | 80a | 57a | 57a | 6b | 3b | ||||||
ASA 3 status (%) | 0a | 10a | 10a | 4a | 76b | 72b | ||||||
ASA 4 status (%) | 0a | 0a | 0a | 0a | 18b | 25b |