Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) Trial
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ClinicalTrials.gov Identifier: NCT03389555 |
Recruitment Status :
Completed
First Posted : January 3, 2018
Results First Posted : January 29, 2021
Last Update Posted : February 16, 2021
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Condition or disease | Intervention/treatment | Phase |
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Sepsis Septic Shock Metabolic Disturbance | Drug: vitamin C, vitamin B1, hydrocortisone Drug: Normal saline | Phase 2 Phase 3 |
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) |
Actual Enrollment : | 205 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 |
Actual Primary Completion Date : | November 26, 2019 |
Actual Study Completion Date : | February 28, 2020 |

Arm | Intervention/treatment |
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Experimental: Vitamin C, Vitamin B1, Corticosteroids
The combination of vitamin C, vitamin B1, hydrocortisone :
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Drug: vitamin C, vitamin B1, hydrocortisone
Vitamin C (1.5g) plus vitamin B1 (100mg) will be diluted in 100ml 0.9% NACL(normal saline) 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:
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Placebo Comparator: Placebo
Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components
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Drug: Normal saline
Normal saline (0.9% NaCl solution) volume to match all components |
- Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours [ Time Frame: Enrollment to 72-hours ]Sequential Organ Failure Assessment (SOFA) Score at Baseline and 72 Hours. The SOFA score ranges from a minimum of 0 to a maximum of 24, with higher scores meaning worse outcomes.
- Renal Failure [ Time Frame: Enrollment until 7-days or discharge from the ICU ]
Development of renal failure as defined by a Kidney Disease Improving Global Outcomes [KDIGO] stage 3 or higher. There are 3 stages in the KDIGO scale with stage 3 being the worst (corresponds to renal failure).
Stage 1- serum creatinine 1.5 to 1.9 times baseline OR an increase in serum creatinine ≥ 0.3 mg/dL OR urine output < 0.5ml/kg/hour for 6-12 hours. Stage 2- serum creatinine 2.0-2.9 times baseline OR urine output <0.5mg/kg/hour for ≥ 12 hours Stage 3- serum creatinine 3.0 times baseline (or serum creatinine of more than or equal to 4.0 mg/dl with an acute increase of at least 0.5 mg/dl) (OR) Urine output less than 0.3 ml/kg/hour for 24 hours or anuria for 12 hours or new renal replacement therapy
- 30-day Mortality [ Time Frame: Enrollment until 30-days after enrollment ]Mortality rate
- Ventilator Free Days [ Time Frame: Ventilator free days over the first 7-days after enrollment ]Days not receiving invasive mechanical ventilation
- Shock Free Days [ Time Frame: Vasopressor free days over the first 7-days after enrollment ]Days not receiving vasopressor
- ICU Free Days [ Time Frame: From enrollment until 28 days after enrollment ]Number of days that the patient was not in the ICU. Timeframe listed below.
- Hospital Mortality [ Time Frame: Enrollment until hospital discharge, death, or 30-days. Whichever comes first. ]Hospital mortality rate
- Intensive Care Unit (ICU) Mortality [ Time Frame: Enrollment until ICU discharge, death, or 30-days. Whichever comes first. ]ICU mortality rate
- Number of Participants With Delirium [ Time Frame: On day 3 (at approximately 72 hours) after the first study drug dose ]
Describes if patient has delirium as defined by the Confusion Assessment Method (CAM)-ICU. The CAM-ICU method requires that the patient have 3 features to qualify for delirium:
- Acute Onset of Changes or Fluctuations in the Course of Mental Status (AND )
- Inattention (AND)
- Disorganized thinking (OR) Altered Level of Consciousness
- Hospital Disposition: Survivors Discharged Home [ Time Frame: Enrollment until hospital discharge, death, or 30-days, whichever comes first. ]Home hospital disposition in patients who survive to discharge

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, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adult patient (age ≥ 18 years)
- Suspected (cultures drawn and antibiotic given) or confirmed (via culture results) infection
- Receiving vasopressor (norepinephrine, phenylephrine, epinephrine, dopamine, angiotensin II or vasopressin)
Exclusion Criteria:
- Member of a protected population (pregnant, prisoner)
- Known kidney stones within the past 1 year (except for asymptomatic, incidentally noted stones on imaging)
- End stage renal disease (ESRD) requiring dialysis
- Known Glucose-6-Phosphate Dehydrogenase deficiency
- Known Hemachromatosis
- Comfort Measures Only status
- Anticipated death within 24-hours despite maximal therapy (as determined by the enrolling physician)
- Receiving supplemental thiamine in a dose greater than that contained in a multivitamin
- Clinical indication for steroids (e.g. chronic use) as determined by the clinical team providing this drug
- Clinical indication for thiamine as determined by the clinical team providing this drug
- Clinical indication for ascorbic acid as determined by the clinical team providing this drug
- Known allergy to vitamin C, hydrocortisone, or thiamine

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
United States, Arizona | |
Mayo Clinic - Arizona | |
Phoenix, Arizona, United States, 85054 | |
United States, Massachusetts | |
Brigham and Women's Hospital | |
Boston, Massachusetts, United States, 02115 | |
Beth Israel Deaconess Medical Center | |
Boston, Massachusetts, United States, 02215 | |
Mount Auburn Hospital | |
Cambridge, Massachusetts, United States, 02138 | |
United States, Michigan | |
Detroit Receiving Hospital | |
Detroit, Michigan, United States, 48201 | |
Harper University Hospital | |
Detroit, Michigan, United States, 48201 | |
Henry Ford Hospital | |
Detroit, Michigan, United States, 48202 | |
Sinai Grace Hospital | |
Detroit, Michigan, United States, 48235 | |
Beaumont Hospital | |
Royal Oak, Michigan, United States, 48073 | |
United States, New York | |
North Shore University Hospital | |
Manhasset, New York, United States, 11030 | |
Long Island Jewish Hospital | |
New York, New York, United States, 11040 | |
United States, Pennsylvania | |
University Of Pittsburgh Medical Center | |
Pittsburgh, Pennsylvania, United States, 15213 | |
United States, Texas | |
The University of Texas Health Science Center | |
Houston, Texas, United States, 77030 |
Principal Investigator: | Michael W Donnino, MD | Beth Israel Deaconess Medical Center |
Documents provided by Michael Donnino, Beth Israel Deaconess Medical Center:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Michael Donnino, Associate Professor of Emergency Medicine, Beth Israel Deaconess Medical Center |
ClinicalTrials.gov Identifier: | NCT03389555 |
Other Study ID Numbers: |
2017P000436 |
First Posted: | January 3, 2018 Key Record Dates |
Results First Posted: | January 29, 2021 |
Last Update Posted: | February 16, 2021 |
Last Verified: | January 2021 |
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 |
Sepsis Metabolic Resuscitation |
Sepsis Toxemia Shock, Septic Infections Systemic Inflammatory Response Syndrome Inflammation Pathologic Processes Shock Vitamins Ascorbic Acid |
Thiamine Hydrocortisone Micronutrients Physiological Effects of Drugs Anti-Inflammatory Agents Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents Vitamin B Complex |