ClinicalTrials.gov
ClinicalTrials.gov Menu

Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03389555
Recruitment Status : Recruiting
First Posted : January 3, 2018
Last Update Posted : April 24, 2018
Sponsor:
Collaborator:
Open Philanthropy Project
Information provided by (Responsible Party):
Michael Donnino, Beth Israel Deaconess Medical Center

Brief Summary:
In this study, we aim to determine whether the combination of Ascorbic Acid (Vitamin C), Thiamine (Vitamin B1), and Corticosteroids improves the trajectory of organ failure and reduces mortality in patients with sepsis and septic shock as compared to placebo.

Condition or disease Intervention/treatment Phase
Sepsis Septic Shock Metabolic Disturbance Drug: vitamin C, vitamin B1, hydrocortisone Drug: Normal saline Phase 2 Phase 3

Detailed Description:

Sepsis and Septic Shock are common and highly morbid clinical conditions without any specific therapy aside from antibiotics. A recent quasi-experimental study (Marik et. al., PMID 27940189) demonstrated a remarkable benefit when the combination of Ascorbic Acid (Vitamin C), Corticosteroids, and Thiamine (Vitamin B1) were given to patients with sepsis. In particular, patients who received this combination of medications required a shorter amount of time on vasopressors, suffered less organ failure, and had improved mortality. Vitamin C has long been suggested for treatment of patients with severe infection as it exerts significant anti-oxidant effects and reduces endothelial permeability. Corticosteroids, a mainstay of therapy for refractory shock in sepsis, have also been shown to enhance the beneficial cellular effects of vitamin C. Finally, thiamine has been shown to be an effective mitochondrial resuscitator in sepsis, especially for the ~30% of septic shock patients who present with thiamine deficiency (Donnino et. al, PMID 26771781).

In this study, we aim to reproduce the findings of Marik et. al. using a more rigorous study design (i.e. a blinded, randomized clinical trial) and focus on the important clinical outcomes of organ failure and death.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ascorbic Ccid, Hydrocortisone, and Thiamine in Sepsis and Septic Shock - A Randomized, Double-Blind, Placebo-Controlled Trial
Actual Study Start Date : February 9, 2018
Estimated Primary Completion Date : June 30, 2019
Estimated Study Completion Date : September 30, 2019


Arm Intervention/treatment
Experimental: Vitamin C, Vitamin B1, Corticosteroids

The combination of vitamin C, vitamin B1, hydrocortisone :

  • Vitamin C (ascorbic acid) 1.5g every 6 hours x 4-days
  • Vitamin B1 (thiamine) 100mg every 6 hours x 4-days
  • Hydrocortisone 50mg every 6 hours x 4-days
Drug: vitamin C, vitamin B1, hydrocortisone
Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9%NACL and administered IV every 6 hours for 4 days or until participant is discharged from the ICU. Hydrocortisone 50mg/ml will be administered via IV push over 1-2 minutes every 6hours for 4 days or until the patient is discharged from the ICU.
Other Names:
  • Ascorbic Acid
  • Thiamine
Placebo Comparator: Placebo
Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components
Drug: Normal saline
Normal saline (0.9% NaCl solution) volume to match all components



Primary Outcome Measures :
  1. Sequential Organ Failure Assessment (SOFA) Score Change [ Time Frame: Enrollment to 72-hours ]
    Change in degree of organ dysfunction as defined by the Sequential Organ Failure Assessment (SOFA) Score


Secondary Outcome Measures :
  1. Renal Failure [ Time Frame: Enrollment until discharge from the ICU ]
    Development of renal failure as defined by a Kidney Disease Improving Global Outcomes [KDIGO] grade 3 or higher

  2. 30-day mortality [ Time Frame: Enrollment until 30-days after enrollment ]
    Mortality rate


Other Outcome Measures:
  1. Ventilator free days [ Time Frame: Ventilator free days over the first 7-days after enrollment ]
    Days not receiving invasive mechanical ventilation

  2. Vasopressor free days [ Time Frame: Vasopressor free days over the first 7-days after enrollment ]
    Days not receiving vasopressor

  3. Length of ICU stay [ Time Frame: Enrollment until ICU discharge ]
    Number of days in the ICU during the index ICU admission

  4. Length of Hospital stay [ Time Frame: Enrollment until hospital discharge ]
    Number of days in the hospital during the index hospital admission

  5. Delirium [ Time Frame: Day 3 of hospital stay ]
    Incidence of delirium

  6. Quality of life [ Time Frame: 90-days after enrollment ]
    Quality of life as assessed by the SF-36 quality-of-life survey



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult patient (age ≥ 18 years)
  2. Suspected (cultures drawn and antibiotic given) or confirmed (via culture results) infection
  3. Receiving vasopressor (norepinephrine, phenylephrine, epinephrine, dopamine, or vasopressin)

Exclusion Criteria:

  1. Member of a protected population (pregnant, prisoner)
  2. Known kidney stones within the past 1 year
  3. Chronic kidney disease (CKD stage ≥3b and above)
  4. Known Glucose-6-Phosphate Dehydrogenase deficiency
  5. Known Hemachromatosis
  6. Comfort Measures Only status
  7. Anticipated death within 24-hours despite maximal therapy (as determined by the enrolling physician)
  8. Receiving supplemental thiamine in a dose greater than that contained in a multivitamin
  9. Clinical indication for steroids (e.g. chronic use) as determined by the clinical team providing this drug
  10. Clinical indication for thiamine as determined by the clinical team providing this drug
  11. Known allergy to vitamin C, hydrocortisone, or thiamine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03389555


Contacts
Contact: Michael W. Donnino, MD 617-754-2341 mdonnino@bidmc.harvard.edu
Contact: Derek P. Guanaga 617-754-2881 dguanaga@bidmc.harvard.edu

Locations
United States, Arizona
Mayo Clinic - Arizona Not yet recruiting
Phoenix, Arizona, United States, 85054
Contact: Ayan Sen, MD         
United States, Massachusetts
Brigham and Women's Hospital Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Peter Hou, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Ari Moskowitz, MD    617-754-3464    amoskowitz@bidmc.harvard.edu   
Contact: Derek P Guanaga    617-754-2881    dguanaga@bidmc.harvard.edu   
Principal Investigator: Michael W Donnino, MD         
Mount Auburn Hospital Not yet recruiting
Cambridge, Massachusetts, United States, 02138
Contact: Jessica McCannon, MD         
United States, Michigan
Detroit Receiving Hospital Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Robert Sherwin, MD         
Harper University Hospital Not yet recruiting
Detroit, Michigan, United States, 48201
Contact: Robert Sherwin, MD         
Henry Ford Hospital Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Bruno DiGiovine, MD         
Sinai Grace Hospital Not yet recruiting
Detroit, Michigan, United States, 48235
Contact: Robert Sherwin, MD         
Beaumont Hospital Not yet recruiting
Royal Oak, Michigan, United States, 48073
Contact: Ronald Otero, MD         
United States, New York
North Shore University Hospital Not yet recruiting
Manhasset, New York, United States, 11030
Contact: Jonathan Gong, MD         
Long Island Jewish Hospital Not yet recruiting
New York, New York, United States, 11040
Contact: Jonathan Gong, MD         
United States, Pennsylvania
University Of Pittsburgh Medical Center Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
The University of Texas Health Science Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Pratik Doshi, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Open Philanthropy Project
Investigators
Principal Investigator: Michael W Donnino, MD Beth Israel Deaconess Medical Center

Publications:
Responsible Party: Michael Donnino, Associate Professor of Emergency Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT03389555     History of Changes
Other Study ID Numbers: 2017P000436
First Posted: January 3, 2018    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Michael Donnino, Beth Israel Deaconess Medical Center:
Sepsis
Metabolic Resuscitation

Additional relevant MeSH terms:
Sepsis
Toxemia
Shock, Septic
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Shock
Vitamins
Ascorbic Acid
Thiamine
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents