Thiamine as a Metabolic Resuscitator After Cardiac Arrest (THACA)

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on lactate, cellular oxygen consumption, global oxygen consumption and biomarkers of neurologic injury after out-of-hospital cardiac arrest (OHCA). .

Study Overview

• Status: Terminated
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: Thiamine 500 mg IV; Other: Placebo

Detailed Description

This is a randomized, double-blind, placebo controlled study to investigate the effect of intravenous thiamine (vitamin B1) on lactate, cellular oxygen consumption, global oxygen consumption and biomarkers of neurologic injury after out-of-hospital cardiac arrest (OHCA). Patients who have sustained return of spontaneous circulation (ROSC) after OHCA and have a lactate of 3 or greater will be eligible for the study. Enrolled patients will be randomized to intravenous thiamine 500mg twice daily for 5 doses or matching placebo (100cc normal saline). Blood will be drawn at several time points and patients will be connected to a noninvasive monitor for continuous measurement of global oxygen consumption. The primary endpoint is change in lactate level. Secondary endpoints include change in pyruvate dehydrogenase activity, change in cellular and global oxygen consumption, change in NSE and S100 (biomarkers of neurologic injury) and CPC-E score (a score that assesses neurologic and functional impairment) at hospital discharge, 30 and 90 days.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patient (age ≥ 18 years)
• Cardiac arrest occurring with sustained (> 20 minutes) return of spontaneous circulation (ROSC)
• Within 4.5 hours of cardiac arrest event
• Lactate >/=3

Exclusion Criteria:

• Clinical indication for thiamine administration (alcoholism, known or highly suspected deficiency) or treatment with thiamine beyond the amount found in a standard multivitamin within the last 10 days
• Traumatic etiology of arrest
• Comfort measures only or anticipated withdrawal of support within 24 hours
• Protected populations (pregnant women, prisoners)
• Known allergy to thiamine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Thiamine; Patients randomized to the thiamine arm will receive thiamine 500mg in 100mL of normal saline intravenously every 12 hours for 5 doses. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.	Drug: Thiamine 500 mg IV; Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.; Other Names: vitamin B1
Placebo Comparator: Placebo; Patients randomized to placebo will receive 100mL normal saline intravenously every 12 hours for 5 doses. All other aspects of the protocol will be the same as in the experimental arm. Patients will be connected to a noninvasive monitor for measurement of global oxygen consumption (VO2) for at least 48 hours or until extubated, whichever comes first. Blood will be drawn at 0,6,12,24,72 and 168 hours for measurement of lactate, thiamine level, pyruvate dehydrogenase, NSE, S100 and other markers of organ injury. CPC-E score will be assessed prior to hospital discharge and at 30 and 90 days to evaluate differences in neurologic and functional impairment.	Other: Placebo; 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm; Other Names: Normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lactate	Blood Lactate Over Time	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Oxygen Consumption	Global Oxygen Consumption over Time	48 hours
Lactate	Absolute Blood Level of Lactate	72 hours
Pyruvate Dehydrogenase (PDH) Specific Activity	Absolute PDH specific activity value	72 hours
Pyruvate Dehydrogenase (PDH) Activity	Absolute PDH Activity Value	72 hours
Pyruvate Dehydrogenase (PDH) Quantity	Absolute PDH Quantity. Please note that the measurement of Absolute PDH Quantity is done using a relative quantity assay, and that PDH is an enzyme and not a stable protein; therefore the units of measure cannot be provided in "mg" and are instead listed in "mini OD unit/min/mg protein".	72 hours
Mortality	Mortality in the study assessed at three timepoints.	will be assessed at hospital discharge and up to 30 and 90 days.
Favorable Cerebral Performance Category (CPC)	Count/Proportion of Patients Scoring a Favorable CPC, defined as a score of 1 or 2. Cerebral performance category scores range from 1-5. Lower scores mean better outcomes.	will be assessed up to 30 and 90 days
Sequential Organ Failure Assessment (SOFA) Score	SOFA score over time. SOFA score: Sequential Organ Failure Assessment Score, ranges from 0-24, higher scores mean worse outcomes.	over 72 hours
Acute Renal Failure	Determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria for Stage 3 acute kidney injury/kidney failure.	First 7 days following Arrest
Cellular Oxygen Consumption	Absolute Cellular Oxygen Consumption Rate: We use two measures to capture Oxygen Consumption Rate; the basal respiration and the maximal respiration.	0 hours and 24 hours.
Creatinine	Creatinine over Time	72 hours
Biomarkers of Neurologic Injury	S100 and NSE levels at various time points	various time points over 7 days

Collaborators and Investigators

• Sponsor: Michael Donnino
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Michael W Donnino, MD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2018
• Primary Completion (Actual): February 19, 2022
• Study Completion (Actual): February 19, 2022

Study Registration Dates

• First Submitted: February 21, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: cardiac arrest; post-arrest
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 2017P000245; 1R01HL136705-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No