Clinical trial NCT03450707: Thiamine as a Metabolic Resuscitator After Cardiac Arrest
Official title: Thiamine as a Metabolic Resuscitator After Cardiac Arrest
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cardiac Arrest
Keywords: cardiac arrest
post-arrest
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-03-01
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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). .

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.

Eligibility 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

Primary outcomes:
measure: Lactate
timeFrame: 24 hours
Secondary outcomes:
measure: Global Oxygen Consumption
timeFrame: 48 hours
measure: Lactate
timeFrame: 72 hours
measure: Pyruvate Dehydrogenase (PDH) Specific Activity
timeFrame: 72 hours
measure: Pyruvate Dehydrogenase (PDH) Activity
timeFrame: 72 hours
measure: Pyruvate Dehydrogenase (PDH) Quantity
timeFrame: 72 hours
measure: Mortality
timeFrame: will be assessed at hospital discharge and up to 30 and 90 days.
measure: Favorable Cerebral Performance Category (CPC)
timeFrame: will be assessed up to 30 and 90 days
measure: Sequential Organ Failure Assessment (SOFA) Score
timeFrame: over 72 hours
measure: Acute Renal Failure
timeFrame: First 7 days following Arrest
measure: Cellular Oxygen Consumption
timeFrame: 0 hours and 24 hours.
measure: Creatinine
timeFrame: 72 hours
measure: Biomarkers of Neurologic Injury
timeFrame: various time points over 7 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Michael W Donnino, MD
role: PRINCIPAL_INVESTIGATOR
References: