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

NCT03389555 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2017P000436
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 13

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.

Conditions

Sepsis; Septic Shock; Metabolic Disturbance

Keywords

Sepsis; Metabolic Resuscitation

Outcome Measures

Primary Outcomes (1)

• Sequential Organ Failure Assessment (SOFA) Score at Baseline and 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.

  Enrollment to 72-hours

Secondary Outcomes (2)

• Renal Failure

  Enrollment until 7-days or discharge from the ICU

• 30-day Mortality

  Enrollment until 30-days after enrollment

Other Outcomes (7)

• Ventilator Free Days

  Ventilator free days over the first 7-days after enrollment

• Shock Free Days

  Vasopressor free days over the first 7-days after enrollment

• ICU Free Days

  From enrollment until 28 days after enrollment

Study Arms (2)

Vitamin C, Vitamin B1, Corticosteroids

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Normal Saline Solution (0.9%NaCl) in a volume to match all experimental arm components

Drug: Normal saline

Interventions

vitamin C, vitamin B1, hydrocortisone DRUG

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.

Also known as: Ascorbic Acid, Thiamine

Vitamin C, Vitamin B1, Corticosteroids

Normal saline DRUG

Normal saline (0.9% NaCl solution) volume to match all components

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Open Philanthropy: collaborator

Study Sites (13)

Mayo Clinic - Arizona

Phoenix, Arizona, 85054, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mount Auburn Hospital

Cambridge, Massachusetts, 02138, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Harper University Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Sinai Grace Hospital

Detroit, Michigan, 48235, United States

Location

Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Long Island Jewish Hospital

New York, New York, 11040, United States

Location

University Of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

Related Publications (6)

• Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun;151(6):1229-1238. doi: 10.1016/j.chest.2016.11.036. Epub 2016 Dec 6.

  PMID: 27940189 BACKGROUND

• Moskowitz A, Andersen LW, Cocchi MN, Karlsson M, Patel PV, Donnino MW. Thiamine as a Renal Protective Agent in Septic Shock. A Secondary Analysis of a Randomized, Double-Blind, Placebo-controlled Trial. Ann Am Thorac Soc. 2017 May;14(5):737-741. doi: 10.1513/AnnalsATS.201608-656BC.

  PMID: 28207287 BACKGROUND

• Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.

  PMID: 26771781 BACKGROUND

• Grossestreuer AV, Moskowitz A, Andersen LW, Holmberg MJ, Konacki V, Berg KM, Chase M, Cocchi MN, Donnino MW. Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Health-Related Quality of Life in Sepsis. Crit Care Explor. 2020 Nov 23;2(12):e0270. doi: 10.1097/CCE.0000000000000270. eCollection 2020 Dec.

  PMID: 33251516 DERIVED

• Moskowitz A, Huang DT, Hou PC, Gong J, Doshi PB, Grossestreuer AV, Andersen LW, Ngo L, Sherwin RL, Berg KM, Chase M, Cocchi MN, McCannon JB, Hershey M, Hilewitz A, Korotun M, Becker LB, Otero RM, Uduman J, Sen A, Donnino MW; ACTS Clinical Trial Investigators. Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial. JAMA. 2020 Aug 18;324(7):642-650. doi: 10.1001/jama.2020.11946.

  PMID: 32809003 DERIVED

• Moskowitz A, Yankama T, Andersen LW, Huang DT, Donnino MW, Grossestreuer AV; ACTS Clinical Trial Investigators. Ascorbic Acid, Corticosteroids and Thiamine in Sepsis (ACTS) protocol and statistical analysis plan: a prospective, multicentre, double-blind, randomised, placebo-controlled clinical trial. BMJ Open. 2019 Dec 17;9(12):e034406. doi: 10.1136/bmjopen-2019-034406.

  PMID: 31852712 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Ascorbic Acid; Thiamine; Hydrocortisone; Saline Solution

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

Ongoing or planned corticosteroid use was the most common exclusion criterion, perhaps eliminating a subset of patients more likely to benefit from corticosteroids. Some patients were discharged alive from the ICU within 96 hours of enrollment; thus, many patients did not receive a full 4 days of study drug

Results Point of Contact

• Title: Michae Donnino
• Organization: Beth Israel Deaconness Medical Center Emergency Department

mdonnino@bidmc.harvard.edu

(617) 754-2882

Study Officials

• Michael W Donnino, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Emergency Medicine

Study Record Dates

• First Submitted: December 27, 2017
• First Posted: January 3, 2018
• Study Start: February 9, 2018
• Primary Completion: November 26, 2019
• Study Completion: February 28, 2020
• Last Updated: February 16, 2021
• Results First Posted: January 29, 2021

Record last verified: 2021-01

Locations

US (13)