High versus gradually increasing energy nutrition in the early phase of acute pancreatitis (GOULASH): a multicentre double-blind randomised clinical trial

Clinical Snapshot

Key Findings

• P Value: 0.42 (corrected for multiple testing)

• Effect Size: Risk difference 3.3% favouring gradual energy approach

• Primary Outcome: Composite mortality and severe acute pancreatitis: HE 9.0% vs LE 5.7%

• Nnt Or Sensitivity: Not calculable due to non-significant primary outcome

• Confidence Interval: Not reported

Clinical Application

Highly feasible - gradual energy approach is standard practice and requires no special resources Directly applicable to Australian emergency departments and gastroenterology units. Supports current RACGP and gastroenterology society recommendations for conservative nutritional management in acute pancreatitis Adult patients with acute pancreatitis of any severity requiring hospitalisation and enteral nutrition

Abstract

BACKGROUND: Acute pancreatitis (AP) is among the most common gastrointestinal diseases requiring hospitalisation, often with severe outcomes and no disease-specific therapy. Nutritional support has been proven to improve outcome, but little is known regarding optimal timing and composition. OBJECTIVE: This clinical trial aimed to compare high (30 kcal/kg/day, high energy (HE)) versus gradually increasing energy (0 increased to 30 kcal/kg/day over 4 days, low energy (LE)) strategies for enteral nutritional support in AP. DESIGN: This was a multicentric, double-blind, randomised clinical trial, enrolling patients with AP regardless of predicted severity (January 2017 to April 2023). The primary outcome was a combination of mortality and severe acute pancreatitis (Revised Atlanta Criteria); secondary outcomes included severity, rate of infection, organ failure and pain relapse. Interim analysis was planned after 50% enrolment. The Benjamini-Hochberg false discovery rate (FDR) method was used to correct p value for multiple testing. RESULTS: The trial was stopped early after enrolling 636 patients. Interim analysis showed that the primary outcome showed no difference between groups in the modified intention-to-treat (mITT) population (HE: 28/312, 9.0% vs LE: 18/307, 5.7%, p(uncorrected/corrected)=0.19/0.42). Secondary outcomes showed no difference in the mITT analysis. Without correction for multiplicity testing, results favoured a low gradual energy strategy in terms of organ failure (HE: 52/312, 16.7% vs LE: 28/307, 9.1%, p(uncorrected)=0.007) and pain relapse (80/312, 27.1% vs 54/307, 19.0% p(uncorrected)=0.03) but showed no differences between groups after correction for multiple testing (p=0.13 and p=0.23, respectively). It was determined that the superiority of the intervention would not be shown even with an increased sample size, and thus the trial was terminated based on a post hoc decision on ethics and futility. CONCLUSION: Based on this early terminated trial, a high-energy strategy for early nutrition in pancreatitis does not decrease mortality/severity, but potentially increases organ failure and pain relapse rate. TRIAL REGISTRATION NUMBER: ISRCTN63827758.

References

1. 1.Márta, K., Engh, M. A., Vincze, Á., Erőss, B., Hegyi, P. J., Mikó, A., Izbéki, F., Papp, M., Mátrai, P., Abonyi-Tóth, Z., Faluhelyi, N., Szentesi, A., & Hegyi, P. (2026). High versus gradually increasing energy nutrition in the early phase of acute pancreatitis (GOULASH): a multicentre double-blind randomised clinical trial. Gut. https://doi.org/10.1136/gutjnl-2025-335970