Abstract
BACKGROUND: The aim of this study was to investigate whether high-dose intravenous vitamin C (HDIVC) could decrease the mortality rate within 28 days among patients moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS: In this randomized, placebo-controlled trial, patients diagnosed with predicted MSAP or SAP within 72 h of symptom onset were enrolled to receive either a vitamin C infusion (200 mg/kg/24 h) or a matched placebo for 7 days. The primary outcome was 28-day mortality. RESULTS: 212 adults including 155 MSAP and 57 SAP were enrolled from September 2019 to June 2023. The trial was terminated prematurely due to a lower than expected 28-day mortality rate which showed no difference between the HDIVC and Control group (3/109 vs. 4/103, unadjusted OR: 0.70, 95% CI, 0.15-3.21, p = 0.647). Among patients with MSAP, the HDIVC group exhibited a more pronounced reduction in C-reactive protein levels compared to the Control group (Day0 to Day3, median 72 mg/L vs. 46 mg/L, p = 0.003; Day0 to Day7, median 168 mg/L vs. 121 mg/L, p = 0.013); The volume of fluid retention was lower in the HDIVC group compared to the Control group (Day0-Day1, median 676.5 ml vs. 1130 ml, P = 0.04; Day0-Day2, median 511 ml vs. 1290 ml, P = 0.02; Day0-Day3, median 692 ml vs. 1534 ml, P = 0.04). The APACHE II scores reduction from Day0 to Day7 was significantly greater in the HDIVC group in APACHE II scores (median change of 3 vs. 2, P = 0.01). No significant difference was observed among patients with SAP. CONCLUSION: HDIVC did not significantly reduce 28-day mortality in MSAP and SAP patients. While it showed potential benefits in reducing CRP, fluid retention, and APACHE II scores in MSAP patients, these effects may not be directly related to the study drug, and no similar changes were observed in SAP patients. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR1900022022. Registered March 21 2019, https//www.chictr.org.cn/showproj.html?proj=37,106 .