Thiamine as a Metabolic Resuscitator After Cardiac Arrest

Cardiac Arrest Clinical Trial

— THACA  

Official title:

Thiamine as a Metabolic Resuscitator After Cardiac Arrest

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03450707
• Other study ID #: 2017P000245
• Secondary ID: 1R01HL136705-01
• Status: Terminated
• Phase: Phase 2
• Start date: May 6, 2018
• Est. completion date: February 19, 2022

Study information

• Verified date: August 2023
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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). .

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 93
• Est. completion date: February 19, 2022
• Est. primary completion date: February 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest

Intervention

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

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Michael Donnino	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lactate	Blood Lactate Over Time	24 hours
Secondary	Global Oxygen Consumption	Global Oxygen Consumption over Time	48 hours
Secondary	Lactate	Absolute Blood Level of Lactate	72 hours
Secondary	Pyruvate Dehydrogenase (PDH) Specific Activity	Absolute PDH specific activity value	72 hours
Secondary	Pyruvate Dehydrogenase (PDH) Activity	Absolute PDH Activity Value	72 hours
Secondary	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
Secondary	Mortality	Mortality in the study assessed at three timepoints.	will be assessed at hospital discharge and up to 30 and 90 days.
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	Creatinine	Creatinine over Time	72 hours
Secondary	Biomarkers of Neurologic Injury	S100 and NSE levels at various time points	various time points over 7 days