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Thiamine as a Metabolic Resuscitator After Cardiac Arrest (THACA)

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ClinicalTrials.gov Identifier: NCT03450707
Recruitment Status : Recruiting
First Posted : March 1, 2018
Last Update Posted : December 9, 2021
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Michael Donnino, Beth Israel Deaconess Medical Center

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
Cardiac Arrest 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 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
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : February 2023

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Normal saline




Primary Outcome Measures :
  1. lactate [ Time Frame: 24 hours ]
    change in blood lactate level over time


Secondary Outcome Measures :
  1. Pyruvate dehydrogenase [ Time Frame: various time points over 72 hours ]
    change in pyruvate dehydrogenase levels over time

  2. global oxygen consumption [ Time Frame: 48 hours ]
    change in global oxygen consumption over time

  3. biomarkers of neurologic injury [ Time Frame: various time points over 7 days ]
    S100 and NSE levels at various time points

  4. cellular oxygen consumption [ Time Frame: various time points over 72 hours ]
    change in cellular oxygen consumption over time

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

  6. Renal failure [ Time Frame: up to 90 days ]
    creatinine and incidence of renal failure requiring renal replacement therapy

  7. Sequential Organ Failure Assessment (SOFA) score [ Time Frame: compared at various time points over 7 days ]
    severity of illness score

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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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): NCT03450707


Contacts
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Contact: Michael W Donnino, MD 617-754-2341 mdonnino@bidmc.harvard.edu
Contact: Katherine M Berg, MD 617-667-5864 kberg@bidmc.harvard.edu

Locations
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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Katherine M Berg, MD    617-667-5864    kberg@bidmc.harvard.edu   
Principal Investigator: Katherine M Berg, MD         
Sponsors and Collaborators
Michael Donnino
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
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Principal Investigator: Michael W Donnino, MD Beth Israel Deaconess Medical Center
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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 ( U.S. NIH Grant/Contract )
First Posted: March 1, 2018    Key Record Dates
Last Update Posted: December 9, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Donnino, Beth Israel Deaconess Medical Center:
cardiac arrest
post-arrest
Additional relevant MeSH terms:
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Heart Arrest
Heart Diseases
Cardiovascular Diseases
Thiamine
Vitamins
Micronutrients
Physiological Effects of Drugs
Vitamin B Complex