Abstract
IMPORTANCE: Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear. OBJECTIVE: To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset. INTERVENTIONS: Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization. RESULTS: Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days (P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis. TRIAL REGISTRATION: ChiCTR.org.cn Identifier: ChiCTR1900023640.