Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at Fresno, California and other locations
Dates
study started
estimated completion

Description

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.

Details

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.

For efficiency, both the Acetaminophen and the Vitamin C groups will use a shared placebo control group. All arms will have the same inclusion and exclusion criteria. All efficacy comparisons will use a pooled placebo group. All safety comparisons will use matching placebo group.

Keywords

Acute Respiratory Distress Syndrome Critical Illness Respiratory Failure Sepsis ARDS Acetaminophen Vitamin C Toxemia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Ascorbic Acid Intravenous Acetaminophen (room temperature) Intravenous Vitamin C (refrigerated) 5% Dextrose (room temperature) 5% Dextrose refrigerated

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Age ≥ 18 years
  2. Sepsis defined as:
  3. Clinical evidence of a known or suspected infection and orders written to administer antibiotics AND
  4. Hypotension as defined by the need for any vasopressor (and 1 liter of fluid already administered) OR respiratory failure defined by assisted ventilation (includes mechanical ventilation and BIPAP), CPAP, or greater than or equal to 6 liters/minute of supplemental oxygen (criterion b must be met at time of enrollment)
  5. Admitted to a study site ICU (or an order written from the ED 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

You CAN'T join if...

  1. No consent/inability to obtain consent from the participant or a legally authorized representative
  2. Patient unable to be randomized within 36 hours of presentation to the ED or within 36 hours of presentation to any acute care hospital
  3. Diagnosis of cirrhosis by medical chart review
  4. Liver transplant recipient
  5. AST or ALT greater than five times upper limit of normal
  6. Diagnosis of ongoing chronic alcohol use disorder/abuse by chart review; if medical record unclear, use Appendix F
  7. Clinical diagnosis of diabetic ketoacidosis or other condition such as profound hypoglycemia that requires hourly blood glucose monitoring
  8. Hypersensitivity to Acetaminophen or Vitamin C
  9. 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)
  10. . Home assisted ventilation (via tracheotomy or noninvasive) except for CPAP/BIPAP used only for sleep-disordered breathing
  11. . Current active kidney stone
  12. . Known history of oxalate kidney stones or history of oxalate nephropathy
  13. . Kidney transplant recipient
  14. . Use of home oxygen for chronic cardiopulmonary disease
  15. . Moribund patient not expected to survive 24 hours
  16. . Underlying malignancy or other condition with estimated life expectancy of less than 1 month
  17. . 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
  18. . Prisoner
  19. . Enrollment in another critical care based pharmacologic interventional trial
  20. . Treating team unwilling to enroll because of intended use of Acetaminophen or Vitamin C

Locations

  • UCSF Fresno
    Fresno California 93701 United States
  • UCSF Medical Center
    San Francisco California 94143 United States

Details

Status
currently not accepting new patients, but might later
Start Date
Completion Date
(estimated)
Sponsor
Massachusetts General Hospital
Links
Website for the PETAL Network
ID
NCT04291508
Phase
Phase 2
Study Type
Interventional
Last Updated