Cardiac ArrestPhase 2THACANCT03450707

Thiamine as a Metabolic Resuscitator After Cardiac Arrest

A Phase 2 study testing Thiamine 500 mg IV in people with Cardiac Arrest, run by Michael Donnino at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Cardiac Arrest
What is being tested?: Thiamine 500 mg IV
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 93 participants
Where: 1 siteUnited States
Study dates: 6 May 2018to 19 Feb 2022
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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 locations and contacts

1 site in 1 country.

United States1 site

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215

Other trials in United States

About this study

Read the 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.

Conditions: Cardiac Arrest
Being tested: Thiamine 500 mg IV, Placebo
Keywords: cardiac arrest, post-arrest
Medical subject headings: Heart Arrest

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Thiamine 500 mg IVDrug
Also called vitamin B1
Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.
PlaceboOther
Also called Normal saline
100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm

Study groups in NCT03450707
Study group	Role	What they receive
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. Receives: 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. Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Lactate
Blood Lactate Over Time
Measured: 24 hours

Secondary outcomes (12)

Global Oxygen Consumption
Global Oxygen Consumption over Time
Measured: 48 hours
Lactate
Absolute Blood Level of Lactate
Measured: 72 hours
Pyruvate Dehydrogenase (PDH) Specific Activity
Absolute PDH specific activity value
Measured: 72 hours
Pyruvate Dehydrogenase (PDH) Activity
Absolute PDH Activity Value
Measured: 72 hours
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".
Measured: 72 hours
Mortality
Mortality in the study assessed at three timepoints.
Measured: will be assessed at hospital discharge and up to 30 and 90 days.
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.
Measured: will be assessed up to 30 and 90 days
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.
Measured: over 72 hours
Acute Renal Failure
Determined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria for Stage 3 acute kidney injury/kidney failure.
Measured: First 7 days following Arrest
Cellular Oxygen Consumption
Absolute Cellular Oxygen Consumption Rate: We use two measures to capture Oxygen Consumption Rate; the basal respiration and the maximal respiration.
Measured: 0 hours and 24 hours.
Creatinine
Creatinine over Time
Measured: 72 hours
Biomarkers of Neurologic Injury
S100 and NSE levels at various time points
Measured: various time points over 7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 May 201819 Feb 2022

First posted1 Mar 2018
Study start6 May 2018
Primary completion19 Feb 2022
Study completion19 Feb 2022

Why it stopped: DSMB recommendation based on differing mortality in a subgroup analysis

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cardiac ArrestStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 93 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03450707
Sponsor's protocol ID: 2017P000245
Other IDs: 1R01HL136705-01
Acronym: THACA
Status last verified: Aug 2023
First submitted: 21 Feb 2018
Last updated: 24 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Assessment of Combined CCM and ICD Device in HFrEF
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Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
Cardiac Arrest (CA), Carotid Doppler
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingObservational study
Evaluation of Acid-base Disorders and Ventilation Settings in Cardiogenic Shock and Post-cardiac Arrest Patients: Comparison With VentilO Algorithm
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All Cardiac Arrest trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Thiamine as a Metabolic Resuscitator After Cardiac Arrest
ClinicalTrials.gov ID: NCT03450707
Acronym / sponsor ID: THACA / 2017P000245
Conditions: Cardiac Arrest
Keywords: cardiac arrest, post-arrest
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: DSMB recommendation based on differing mortality in a subgroup analysis
Enrolment: 93 participants (actual)
Lead sponsor: Michael DonninoUniversity, hospital or other
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Study start: 6 May 2018 (actual)
Primary completion: 19 Feb 2022 (actual)
Study completion: 19 Feb 2022 (actual)
First posted: 1 Mar 2018 (actual)
Results: Posted 24 Aug 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Thiamine	Experimental	Drug: Thiamine 500 mg IVPatients 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.
Placebo	Placebo comparator	Other: PlaceboPatients 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Thiamine 500 mg IVAlso: vitamin B1Thiamine hydrochloride (vitamin B1) 500mg IV will be given every 12 hours for 5 doses in the experimental arm.	Drug	Thiamine
PlaceboAlso: Normal saline100mL of intravenous normal saline will be given every 12hours for 5 doses in the placebo arm	Other	Placebo

Primary outcome

Lactate
Time frame: 24 hours
Blood Lactate Over Time

12 secondary outcomes

Global Oxygen Consumption
Time frame: 48 hours
Lactate
Time frame: 72 hours
Pyruvate Dehydrogenase (PDH) Specific Activity
Time frame: 72 hours
Pyruvate Dehydrogenase (PDH) Activity
Time frame: 72 hours
Pyruvate Dehydrogenase (PDH) Quantity
Time frame: 72 hours
Mortality
Time frame: will be assessed at hospital discharge and up to 30 and 90 days.
Favorable Cerebral Performance Category (CPC)
Time frame: will be assessed up to 30 and 90 days
Sequential Organ Failure Assessment (SOFA) Score
Time frame: over 72 hours
Acute Renal Failure
Time frame: First 7 days following Arrest
Cellular Oxygen Consumption
Time frame: 0 hours and 24 hours.
Creatinine
Time frame: 72 hours
Biomarkers of Neurologic Injury
Time frame: various time points over 7 days

Results and safety

Results posted to the registry on 24 Aug 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Thiamine	47	40
Placebo	46	36

Primary outcome: Lactate

Time frame: 24 hours. Median (Inter-Quartile Range). Unit: mmol/L

Measure	Thiamine n = 29	Placebo n = 30
Value	1.8 (1.2 to 2.4)	2.2 (1.4 to 2.5)

Thiamine vs Placebo: Mean Difference (Final Values): 0.34 (95% CI -1.82 to 2.50), p = 0.72, Mixed Models Analysis

Population analysed: Seventeen patients (six in the placebo arm and eleven in the thiamine arm) missing 24-hour lactate as they had expired by this timepoint.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-Cause Mortality was monitored upto 90 days; Serious and/or Other (Not Including Serious) Adverse Events assessed from enrollment to time of discharge, an average of one week.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Thiamine	0 of 40 (0%)	0 of 40 (0%)	30 of 40
Placebo	0 of 36 (0%)	0 of 36 (0%)	24 of 36

Limitations and caveats (from the sponsor): 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

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Cardiac Arrest

RecruitingObservational study
AI-powered ECG Analysis Using Willem™ Software in High-risk Cardiac Patients (WILLEM)
Cardiomyopathies, Cardiac Arrest
Active, not recruiting
Assessment of Combined CCM and ICD Device in HFrEF
Heart Failure, Heart Failure With Reduced Ejection Fraction
Not yet recruitingObservational study
CAROTID DOPPLER AND CEREBRAL OXIMERY IN POST CARDIAC ARREST ICU PATIENTS
Cardiac Arrest (CA), Carotid Doppler
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingObservational study
Evaluation of Acid-base Disorders and Ventilation Settings in Cardiogenic Shock and Post-cardiac Arrest Patients: Comparison With VentilO Algorithm
Cardiac Arrest (CA), Cardiogenic Shock

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Michael W Donnino, MD principal investigator

Beth Israel Deaconess Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Thiamine 500 mg IV in people with Cardiac Arrest, run by Michael Donnino at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Lactate (time frame: 24 hours). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03450707.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Aug 2023.