The study hypothesis: A very early start of EN, as compared to the current standard of delayed start of EN, will lead to a reduction in morbidity or mortality in patients with predicted severe AP. The primary research question: Does a very early start of EN as compared to the current standard of delayed start of EN lead to a reduction in severe infectious complications or mortality in patients with predicted severe AP?Secondary research question: What is the balance of costs and clinical effects between a very early start of enteral nutrition (EN) and the current standard nutritional management (start of EN after several days) in predicted severe acute pancreatitis? Other secondary research questions: What is the impact of very early EN on the individual components of the primary endpoint? What is the impact of very early EN in terms of clinical outcome; total hospital and intensive care stay, need for percutaneous, surgical or endoscopic necrosectomy, switch from nasogastric to nasojejunal feeding, artificial nutrition related complications and proportion of daily target intake achieved at 1 week?
Pancreatitis, verY early compared wiTH delayed start Of eNteral feeding; PYTHON, a randomised controlled multicenter trial. Dutch Acute Pancreatitis Study Group.1. research question:Primary question: Does a very early start of EN as compared to the current standard of delayed start of EN lead to a reduction in severe infectious complications or mortality in patients with predicted severe AP?Secondary question: What is the balance of costs and clinical effects between a very early start of enteral nutrition (EN) and the current standard nutritional management (start of EN after several days) in predicted severe acute pancreatitis?2. study design:A randomised controlled parallel group superiority multicenter trial in 20 Dutch hospitals3. study population:Patients with predicted severe acute pancreatitis4. intervention:A) Nasogastric EN within 24 hrs after admission versus B) nil per mouth in the first 72 hrs, followed by nasogastric EN or oral feeding when tolerated.5. outcome measures:Primary composite endpoint: the fraction of patients with a severe infectious complication (infected pancreatic necrosis, positive blood culture, pneumonia) or mortality during hospital stay or during 90 days postdischarge follow-up.Secondary endpoints: Medical and indirect costs comparing absolute volumes of resource utilization in relation to outcome (cost-effectiveness analysis), total hospital and intensive care stay, need for and type of intervention, switch from nasogastric to nasojejunal feeding, artificial nutrition related complications, proportion of daily target intake achieved at 1 week.6. sample size calculation:An absolute reduction in severe infectious complications by 17% or a absolute reduction in mortality by 1% is assumed. Combined a reduction of the primary composite endpoint from 40% to 22% is expected. With a 2-sided alpha of 5%, power of 80%, and a loss-to-follow-up of 1% a total 208 patients will be randomized.7. economic evaluationThe balance between costs and effects will be determined in terms of costs per severe infectious complication avoided, death avoided and quality adjusted life year (QALY) gained. The cost-analysis is set up from a societal perspective.8. time schedule:Three year inclusion period including two months for full analysis and reporting of results. |
