Status:

COMPLETED

Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery

Lead Sponsor:

Massachusetts General Hospital

Conditions:

Acute Respiratory Distress Syndrome

Critical Illness

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

Prospective multi-center phase 2b randomized placebo-controlled double-blinded interventional platform trial of two different pharmacologic therapies (intravenous Vitamin C or intravenous Acetaminophe...

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 seco...

Eligibility Criteria

Inclusion

  • Age ≥ 18 years
  • Sepsis defined as:
  • Clinical evidence of a known or suspected infection and orders written to administer antibiotics AND
  • Hypotension as defined by the need for any vasopressor (and 1 liter of fluid already administered intravenously for resuscitation) OR respiratory failure defined by mechanical ventilation, BIPAP or CPAP at any level, or greater than or equal to 6 liters/minute of supplemental oxygen (criterion b must be met at time of enrollment)
  • Admitted to a study site ICU (or intent for the patient to be admitted to a study site ICU) within 36 hours of presentation to the ED or admitted to the study site ICU within 36 hours of presentation to any acute care hospital

Exclusion

  • No consent/inability to obtain consent from the participant or a legally authorized representative
  • Patient unable to be randomized within 36 hours of presentation to the ED or within 36 hours of presentation to any acute care hospital
  • Diagnosis of cirrhosis by medical chart review
  • Liver transplant recipient
  • AST or ALT greater than five times upper limit of normal
  • Diagnosis of ongoing chronic alcohol use disorder/abuse by chart review; if medical record unclear, use Appendix F
  • Clinical diagnosis of diabetic ketoacidosis or other condition such as profound hypoglycemia that requires hourly blood glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
  • Hypersensitivity to Acetaminophen or Vitamin C
  • Patient, surrogate or physician not committed to full support (Exception: a patient will not be excluded if he/she would receive all supportive care except for attempts at resuscitation from cardiac arrest)
  • Home assisted ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing
  • Chronic dialysis
  • Current active kidney stone (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
  • Multiple (\>1) episodes of prior kidney stones, known history of oxalate kidney stones, or history of oxalate nephropathy. (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
  • Kidney transplant recipient (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
  • Use of home oxygen \>3L/minute via nasal cannula for chronic cardiopulmonary disease
  • Moribund patient not expected to survive 24 hours
  • Underlying malignancy or other condition with estimated life expectancy of less than 1 month
  • Pregnant woman, woman of childbearing potential without a documented negative urine or serum pregnancy test during the current hospitalization, or woman who is breast feeding
  • Prisoner
  • Treating team unwilling to enroll because of intended use of Acetaminophen or Vitamin C
  • Treating team unwilling to use plasma (as opposed to point of care testing) for glucose monitoring (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial).

Key Trial Info

Start Date :

October 13 2021

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

July 27 2023

Estimated Enrollment :

488 Patients enrolled

Trial Details

Trial ID

NCT04291508

Start Date

October 13 2021

End Date

July 27 2023

Last Update

September 27 2024

Active Locations (41)

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Page 1 of 11 (41 locations)

1

University of Alabama Medical Center

Birmingham, Alabama, United States, 35249

2

University of Arizona

Tucson, Arizona, United States, 85721

3

UCSF Fresno

Fresno, California, United States, 93701

4

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048