Ascorbic acid, Corticosteroids and Thiamine in Sepsis Study (ACTS)

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Description: a randomized, double-blind, placebo-controlled trial of ascorbic acid, hydrocortisone, and thiamine to improve outcomes in septic shock.

Steering Committee:

Michael W. Donnino (Principal Investigator)

Ari Moskowitz MD

Katherine M. Berg MD

Michael N. Cocchi MD

Anne V. Grossestreuer PhD

Paul Marik, MD

Lars W. Andersen, MD, MPH, PhD

Funding Source:

Open Philanthropy

Status of Study:

Enrolling

Purpose of Protocol:

Our overall hypothesis is that the administration of ascorbic acid, hydrocortisone, and thiamine in septic shock patients will mitigate organ injury through improvement in free radical reduction, immune function, endothelial integrity, and mitochondrial energy production.

Specific Aim – To determine whether the combination of thiamine/ascorbic acid/hydrocortisone administered to patients with shock septic mitigates organ dyfunction as compared to placebo. 

Significance and Background:

Septic shock is a common and highly morbid condition affecting over 200,000 patients in the United States each year and resulting in upwards of 40,000 deaths. In-hospital mortality for patients admitted with septic shock has been has been estimated to be as high as 40%. While there is presently no recommended pharmacologic therapy specifically targeted at attenuating organ injury in septic shock, recent observational studies have found promising results using the combination of ascorbic acid (vitamin C), corticosteroids, and thiamine (vitamin B1). This medication combination has gained traction in the lay-media and is already being used by some hospitals to treat patients with sepsis and septic shock. Prospective testing in a randomized controlled trial, however, is needed prior to the widespread implementation of this therapy for victims of septic shock.

Design:

This prospective, randomized, blinded, placebo-controlled multi-center trial will investigate the effect of ascorbic acid, hydrocortisone, and thiamine vs placebo on organ function in patients with septic shock. We will also evaluate other outcomes including mortality.

Study Sites

Hospital Name	Location
BIDMC	Boston, MA
Henry Ford Hospital	Detroit, MI
DMC-Detroit Receiving Hospital	Detroit, MI
DMC-Sinai-Grace Hospital	Detroit, MI
Harper Hospital	Detroit, MI
UT Health, The University of Texas Health Science Center	Houston, TX
Mayo Clinic	Phoenix, AZ
Beaumont Hospital	Royal Oak, MI
Brigham and Women’s Hospital	Boston, MA
Long Island Jewish Hospital Center - Queens	New York, NY
Long Island Jewish Hospital Center – Hyde Park	New York, NY
Mount Auburn Hospital	Cambridge, MA
University of Pittsburgh	Pittsburgh, PA
South Shore Hospital	South Shore, MA

 

Inclusion Criteria:

1.  Adult (≥ 18 years)
2. Suspected (blood cultures drawn and antibiotics given) or confirmed (via culture results) infection
3. Receiving vasopressor support (norepinephrine, phenylephrine, epinephrine, dopamine, or vasopressin)*Sepsis/Infection should be the suspected precipitant of hypotension requiring vasopressor support.

Exclusion Criteria:

1. Known kidney stones within the past 1 year (not including incidentally noted stones)
2. End Stage Renal Disease requiring renal replacement therapy
3. Known G6PD deficiency or hemochromatosis
4. Comfort Measures Only status or anticipated death within 24-hours despite maximal therapy
5. Clinical indication for steroids, thiamine, or Vitamin C as determined by clinical teams
6. Known allergy to vitamin C, hydrocortisone, or thiamine
7. Protected Population (prisoner, pregnant)

Study Protocol:

All patients will receive standard septic shock care per their clinical team, whether or not they enroll in the study. After consent/enrollment, patients will have baseline labs drawn, and will be administered the study drug or placebo four times daily for four days (or until they leave the ICU).

Blood and Urine sample collection: All patients will have blood samples collected at 0, 24, 72, and 120 hours, with testing as detailed below.

Primary Outcome: The primary outcome will be the Sequential Organ Failure Assessment (SOFA) score. The SOFA score is a measure of organ dysfunction.

Secondary Outcomes:

• Need for renal replacement therapy
• Incidence of delirium
• Vasopressor-free days
• Ventilator-free days
• ICU LOS
• 30-day Mortality
• 90-day cognitive outcomes
• Measurements of other blood and urine marker of organ dysfunction