Thiamine as a Metabolic Resuscitator After Cardiac Arrest

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: February 2023

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.

Interventions

  • 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: Placebo
    • 100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm

Arms, Groups and Cohorts

  • 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.
  • 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.

Clinical Trial Outcome Measures

Primary Measures

  • lactate
    • Time Frame: 24 hours
    • change in blood lactate level over time

Secondary Measures

  • Pyruvate dehydrogenase
    • Time Frame: various time points over 72 hours
    • change in pyruvate dehydrogenase levels over time
  • global oxygen consumption
    • Time Frame: 48 hours
    • change in global oxygen consumption over time
  • biomarkers of neurologic injury
    • Time Frame: various time points over 7 days
    • S100 and NSE levels at various time points
  • cellular oxygen consumption
    • Time Frame: various time points over 72 hours
    • change in cellular oxygen consumption over time
  • Cerebral Performance Category-Extended (score)
    • Time Frame: will be assessed up to 30 and 90 days
    • neurological injury score
  • Renal failure
    • Time Frame: up to 90 days
    • creatinine and incidence of renal failure requiring renal replacement therapy
  • Sequential Organ Failure Assessment (SOFA) score
    • Time Frame: compared at various time points over 7 days
    • severity of illness score
  • Mortality
    • Time Frame: will be assessed up to 30 and 90 days.
    • Mortality

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Michael Donnino
  • Collaborator
    • National Heart, Lung, and Blood Institute (NHLBI)
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Michael Donnino, Associate Professor of Medicine and Emergency Medicine – Beth Israel Deaconess Medical Center
  • Overall Official(s)
    • Michael W Donnino, MD, Principal Investigator, Beth Israel Deaconess Medical Center
  • Overall Contact(s)
    • Michael W Donnino, MD, 617-754-2341, mdonnino@bidmc.harvard.edu

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