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THACA: Thiamine as a Metabolic Resuscitator After Cardiac Arrest

Sponsor
Michael Donnino (Other)
Overall Status
Terminated
CT.gov ID
NCT03450707
Collaborator
National Heart, Lung, and Blood Institute (NHLBI) (NIH)
76
Enrollment
1
Location
2
Arms
45.5
Actual Duration (Months)
1.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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). .

Condition or Disease Intervention/Treatment Phase
  • Drug: Thiamine 500 mg IV
  • Other: Placebo
 Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
76 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
A randomization list was prepared by an independent statistician using 1:1 randomization in blocks of four. This list will be provided to the research pharmacy, and the research pharmacy will be the only unblinded people involved with the study, and will have no patient contact or role in the analysis or other aspects of the study. Thiamine is colorless and odorless, and the 500mg dose is mixed in 100mL of normal saline. Placebo will be 100mL of normal saline and is indistinguishable in appearance from thiamine. Study team, clinical team and patient and family will all be blind to the allocation.
Primary Purpose:
Treatment
Official Title:
Thiamine as a Metabolic Resuscitator After Cardiac Arrest
Actual Study Start Date :
May 6, 2018
Actual Primary Completion Date :
Feb 19, 2022
Actual Study Completion Date :
Feb 19, 2022

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. lactate [24 hours]

      change in blood lactate level over time

    Secondary Outcome Measures

    1. Pyruvate dehydrogenase [various time points over 72 hours]

      change in pyruvate dehydrogenase levels over time

    2. global oxygen consumption [48 hours]

      change in global oxygen consumption over time

    3. biomarkers of neurologic injury [various time points over 7 days]

      S100 and NSE levels at various time points

    4. cellular oxygen consumption [various time points over 72 hours]

      change in cellular oxygen consumption over time

    5. Cerebral Performance Category-Extended (score) [will be assessed up to 30 and 90 days]

      neurological injury score

    6. Renal failure [up to 90 days]

      creatinine and incidence of renal failure requiring renal replacement therapy

    7. Sequential Organ Failure Assessment (SOFA) score [compared at various time points over 7 days]

      severity of illness score

    8. Mortality [will be assessed up to 30 and 90 days.]

      Mortality

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215

    Sponsors and Collaborators

    • Michael Donnino
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Michael W Donnino, MD, Beth Israel Deaconess Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Michael Donnino, Associate Professor of Medicine and Emergency Medicine, Beth Israel Deaconess Medical Center
    ClinicalTrials.gov Identifier:
    NCT03450707
    Other Study ID Numbers:
    • 2017P000245
    • 1R01HL136705-01
    First Posted:
    Mar 1, 2018
    Last Update Posted:
    Aug 19, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Michael Donnino, Associate Professor of Medicine and Emergency Medicine, Beth Israel Deaconess Medical Center
    cardiac arrest
    post-arrest
    Additional relevant MeSH terms:
    Heart Arrest
    Thiamine

    Study Results

    No Results Posted as of Aug 19, 2022