Thiamine as a Metabolic Resuscitator After Cardiac Arrest (THACA)

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

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
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.

Study Design

• 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

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 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

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

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

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

More Information

• 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
• Last Update Posted: December 9, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• 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, Beth Israel Deaconess Medical Center:

cardiac arrest; post-arrest

Additional relevant MeSH terms:

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Thiamine; Vitamins; Micronutrients; Physiological Effects of Drugs; Vitamin B Complex