Acetaminophen and Ascorbate in Sepsis: Targeted Therapy to Enhance Recovery
NCT ID: NCT04291508
Last Updated: 2024-09-27
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
488 participants
INTERVENTIONAL
2021-10-13
2023-07-27
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis
NCT01739361
Heamodynamic Effects of Paracetamol in Septic Shock Patients
NCT06076980
Ascorbic Acid (Vitamin C) Infusion in Human Sepsis
NCT01434121
Paracetamol Toxicity in Septic Patients
NCT01182974
Vitamin C to Reduce Vasopressor Dose in Septic Shock
NCT03835286
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
IV Acetaminophen-Active
Patients randomized to the Acetaminophen arm will receive Acetaminophen at the dose of 1 gram (or 15 mg/kg if actual body weight \< 50kg) in 100 ml 5% dextrose in water every 6 hours intravenously for 5 days (20 doses).
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)
IV Vitamin C-Active
Patients randomized to the Vitamin C arm will receive Vitamin C at the dose of 50 mg/kg in 100 ml 5% dextrose in water every 6 hours intravenously for 5 days (20 doses). Note: This arm is now closed.
Intravenous Vitamin C (refrigerated)
Vitamin C given intravenously at the dose of 50 mg/kg every six hours for 5 days (20 doses)
Acetaminophen-Placebo
Patients randomized to placebo will receive an identical-appearing intravenous infusion of 100 ml of 5% dextrose in water every 6 hours for 5 days (20 doses).
5% Dextrose (room temperature)
Placebo (identical appearing room temperature 5% dextrose solution) infused every six hours for 5 days (20 doses)
Vitamin C-Placebo
Patients randomized to placebo will receive an identical-appearing intravenous infusion of 100 ml of 5% dextrose in water every 6 hours for 5 days (20 doses). Note: This arm is now closed.
5% Dextrose refrigerated
Placebo (identical appearing refrigerated 5% dextrose solution) infused every six hours for 5 days (20 doses)
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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)
Intravenous Vitamin C (refrigerated)
Vitamin C given intravenously at the dose of 50 mg/kg every six hours for 5 days (20 doses)
5% Dextrose (room temperature)
Placebo (identical appearing room temperature 5% dextrose solution) infused every six hours for 5 days (20 doses)
5% Dextrose refrigerated
Placebo (identical appearing refrigerated 5% dextrose solution) infused every six hours for 5 days (20 doses)
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
2. Sepsis defined as:
1. Clinical evidence of a known or suspected infection and orders written to administer antibiotics AND
2. 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)
3. 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 Criteria
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 (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
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. Chronic dialysis
12. Current active kidney stone (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
13. 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)
14. Kidney transplant recipient (applicable to the 4 arm (Vitamin C/placebo vs. Acetaminophen/placebo) phase of the trial)
15. Use of home oxygen \>3L/minute via nasal cannula for chronic cardiopulmonary disease
16. Moribund patient not expected to survive 24 hours
17. Underlying malignancy or other condition with estimated life expectancy of less than 1 month
18. 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
19. Prisoner
20. Treating team unwilling to enroll because of intended use of Acetaminophen or Vitamin C
21. 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).
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Massachusetts General Hospital
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Boyd Taylor Thompson
PETAL CCC Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Boyd Taylor Thompson, MD
Role: PRINCIPAL_INVESTIGATOR
Massachusetts General Hospital
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
University of Alabama Medical Center
Birmingham, Alabama, United States
University of Arizona
Tucson, Arizona, United States
UCSF Fresno
Fresno, California, United States
Cedars-Sinai Medical Center
Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, United States
UC Davis Medical Center
Sacramento, California, United States
UCSF Medical Center
San Francisco, California, United States
Stanford University
Stanford, California, United States
University of Colorado Hospital
Aurora, Colorado, United States
Denver Health Medical Center
Denver, Colorado, United States
University Medical Center
New Orleans, Louisiana, United States
Maine Medical Center
Portland, Maine, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Baystate Medical Center
Springfield, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
Henry Ford Medical Center
Detroit, Michigan, United States
Fairview Southdale Hospital
Edina, Minnesota, United States
Hennepin County Medical Center
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Mt. Sinai Hospital
New York, New York, United States
Montefiore Medical Center-Weiler
The Bronx, New York, United States
Montefiore Medical Center-Moses
The Bronx, New York, United States
Carolinas Medical Center
Charlotte, North Carolina, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Oregon Health and Science University
Portland, Oregon, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
UPMC Presbyterian/Mercy/Shadyside/Magee
Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University of Texas Health Science Center
Houston, Texas, United States
Intermountain Medical Center
Murray, Utah, United States
University of Utah Hospital
Salt Lake City, Utah, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Sentara/EVMS
Norfolk, Virginia, United States
VCU Medical Center
Richmond, Virginia, United States
Harborview Medical Center
Seattle, Washington, United States
Swedish Hospital First Hill
Seattle, Washington, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Ware LB, Files DC, Fowler A, Aboodi MS, Aggarwal NR, Brower RG, Chang SY, Douglas IS, Fields S, Foulkes AS, Ginde AA, Harris ES, Hendey GW, Hite RD, Huang W, Lai P, Liu KD, Thompson BT, Matthay MA; National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial. JAMA. 2024 Aug 6;332(5):390-400. doi: 10.1001/jama.2024.8772.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol: ASTER Protocol version 4.2
Document Type: Study Protocol: ASTER Protocol version 4.5
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form: Stamped-ICD_P1_master_v4
Document Type: Informed Consent Form: Stamped-ICD_P1_master_v5
Document Type: Informed Consent Form: ICD_p2_template
Related Links
Access external resources that provide additional context or updates about the study.
Website for the PETAL Network
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PETAL04ASTER
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.