Thiamine as a Metabolic Resuscitator After Cardiac Arrest

NCT03450707 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2017P0002451R01HL136705-01
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 1

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). .

Conditions

Cardiac Arrest

Keywords

cardiac arrest; post-arrest

Outcome Measures

Primary Outcomes (1)

• Lactate

  Blood Lactate Over Time

  24 hours

Secondary Outcomes (12)

• Global Oxygen Consumption

  48 hours

• Lactate

  72 hours

• Pyruvate Dehydrogenase (PDH) Specific Activity

  72 hours

• Pyruvate Dehydrogenase (PDH) Activity

  72 hours

• Pyruvate Dehydrogenase (PDH) Quantity

  72 hours

Study Arms (2)

Thiamine

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Thiamine 500 mg IV DRUG

Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.

Also known as: vitamin B1

Thiamine

Placebo OTHER

100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm

Also known as: Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Michael Donnino: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Heart Arrest

Interventions

Thiamine; Saline Solution

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

The study was stopped early by the Data Safety and Monitoring Board (DSMB) due to a signal of increased mortality in the thiamine group with a lactate \> 5

Results Point of Contact

• Title: Dr. Michael Donnino
• Organization: BIDMC

mdonnino@bidmc.harvard.edu

6177542882

Study Officials

• Michael W Donnino, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine and Emergency Medicine

Study Record Dates

• First Submitted: February 21, 2018
• First Posted: March 1, 2018
• Study Start: May 6, 2018
• Primary Completion: February 19, 2022
• Study Completion: February 19, 2022
• Last Updated: August 24, 2023
• Results First Posted: August 24, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)