Thiamine as a Metabolic Resuscitator After Cardiac Arrest (THACA)

Michael Donnino

Status and phase: Terminated; Phase 2

Conditions: Cardiac Arrest

Treatments: Drug: Thiamine 500 mg IV; Other: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03450707

1R01HL136705-01 (U.S. NIH Grant/Contract)

2017P000245

Details and patient eligibility

About

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). .

Full 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.

Enrollment: 93 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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93 participants in 2 patient groups, including a placebo group

Thiamine

Experimental group

Description:

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.

Treatment:

Drug: Thiamine 500 mg IV

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Other: Placebo