NCT04291508

Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 488 (actual)
• Sponsor: Massachusetts General Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Prospective multi-center phase 2b randomized placebo-controlled double-blinded interventional platform trial of two different pharmacologic therapies (intravenous Vitamin C or intravenous Acetaminophen) for patients with sepsis-induced hypotension or respiratory failure.

Detailed description

Hypothesis 1A: Acetaminophen (APAP) or Vitamin C infusion will increase the days alive and free of organ support to day 28. Hypothesis 1B: APAP or Vitamin C will have a favorable effect on other secondary outcomes including pulmonary and non-pulmonary organ dysfunction and biomarkers of inflammation and endothelial injury The investigators plan to carry out two multi-center phase 2b randomized double-blinded placebo-controlled trials of two different pharmacologic therapies within a single platform trial. 1. One trial will assess the efficacy of Acetaminophen (1 gram intravenously every 6 hours) for 120 hours in patients with sepsis who have evidence of either hemodynamic or respiratory organ failure. 2. A second trial will assess the efficacy of Vitamin C (50 mg/kg every 6 hours) infused intravenously for 120 hours in patients with sepsis who have evidence of either hemodynamic or respiratory organ failure. A total of 900 participants who meet all of the inclusion criteria and none of the exclusion criteria, were planned be randomized in a 2:1:2:1 fashion (APAP-Active: APAP-Placebo: Vit C-Active: Vit C-Placebo). The APAP and Vitamin C trials were planned to be resulted separately. With the closure of the Vitamin C arm in June 2022; the study proceeded with the APAP and Placebo arms with a 1:1 randomization scheme. The total sample size for the APAP trial was 447 participants (227 in the active arm and 220 in the placebo arm). The total sample size for the Vitamin C trial was 79 (40 in the active arm and 39 in the placebo arm). The total combined number in the 4 arms of the ASTER trial was 526 (227 APAP active, 220 APAP placebo, 40 Vit C active, 39 Vit C placebo), although a total of only 487 patients were actually randomized (this is due to the 39 pooled placebo patients that appear in both trials).

Conditions

• Acute Respiratory Distress Syndrome
• Critical Illness
• Respiratory Failure
• Sepsis

Interventions

Type	Name	Description
DRUG	Intravenous Acetaminophen (room temperature)	Acetaminophen given intravenously at the dose of 1 gram (or 15 mg/kg if patient weighs \< 50 kg) every six hours for 5 days (20 doses)
DRUG	Intravenous Vitamin C (refrigerated)	Vitamin C given intravenously at the dose of 50 mg/kg every six hours for 5 days (20 doses)
DRUG	5% Dextrose (room temperature)	Placebo (identical appearing room temperature 5% dextrose solution) infused every six hours for 5 days (20 doses)
DRUG	5% Dextrose refrigerated	Placebo (identical appearing refrigerated 5% dextrose solution) infused every six hours for 5 days (20 doses)

Timeline

• Start date: 2021-10-13
• Primary completion: 2023-04-27
• Completion: 2023-07-27
• First posted: 2020-03-02
• Last updated: 2024-09-27
• Results posted: 2024-09-27

Locations

41 sites across 1 country: United States

Regulatory

• FDA-regulated drug study