Coronary Artery BypassPhase 2NCT02322892
Thiamine as an Adjunctive Therapy in Cardiac Surgery
A Phase 2 study testing Thiamine and Normal saline solution in people with Coronary Artery Bypass and Cardiac Surgical Procedures, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The main purpose of this pilot study is to test the effects of thiamine (vitamin B1) administration before and after major cardiac surgery. Half of patients will receive thiamine and the other half will receive placebo. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Coronary Artery Bypass, Cardiac Surgical Procedures
- What is being tested?
- Thiamine and Normal saline solution
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Aug 2015
- 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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult (≥ 21 years)
- Coronary artery bypass grafting (CABG) with or without concomitant valve procedures
- EuroSCORE II > 1.5%
Who cannot join
- Current thiamine supplementation
- Known allergy to thiamine
- Competing indication for thiamine administration as judged by the clinical team (e.g., alcoholic)
- Research-protected populations (pregnant women, prisoners, the intellectually disabled)
- Emergent or salvage CABG (as defined by the Society of Thoracic Surgeons)
- Off-pump surgery (i.e. surgery without cardiopulmonary bypass)
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
The main purpose of this pilot study is to test the effects of thiamine (vitamin B1) administration before and after major cardiac surgery. Half of patients will receive thiamine and the other half will receive placebo.
The investigators' main hypothesis is that thiamine will improve cellular oxygen consumption and lead to decreased levels of post-operative lactate levels and ultimately improved patient outcomes.
Read the detailed description
Over 230,000 patients in the United States undergo Coronary Artery Bypass Grafting (CABG) each year. While mortality is relatively low, morbidity remains substantial with a significant risk of prolonged time on mechanical ventilation, prolonged length of hospital and intensive care unit stay and many other complications. CABG causes a profound stress response and significant metabolic alterations occur, including a shift from aerobic to anaerobic metabolism, causing increased levels of pyruvate and lactate. Elevated lactate, a marker of anaerobic metabolism, is a common and significant finding in patients after CABG and is correlated with increased mortality and morbidity.
Aerobic metabolism occurs when pyruvate enters the mitochondria through pyruvate decarboxylation to acetyl-Coenzyme A, facilitated by the enzyme pyruvate dehydrogenase (PDH). Decreased PDH activity may cause a shift toward anaerobic metabolism and play a role in the changes seen in patients undergoing CABG. Thiamine (vitamin B1) is a key co-factor for PDH function and will increase activity even in non-deficient states. The investigators hypothesize that thiamine administration will increase PDH activity in patients undergoing CABG, leading to increased cellular oxygen consumption, as represented by decreased lactate levels after surgery, and ultimately improved clinical outcomes.
In order to test the investigators' hypothesis and to obtain data for a large-scale clinical trial evaluating relevant clinical endpoints, the investigators are conducting a randomized, double-blind, pilot trial of thiamine in high-risk patients undergoing CABG.
- Being tested
- Thiamine, Normal saline solution
- Keywords
- Thiamine, Vitamin B1, Coronary artery bypass grafting, Cardiac surgery, Lactate, Pyruvate dehydrogenase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThiamineDrug
Also called vitamin B1, Thiamin
200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)
Normal saline solutionDrug
50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)
| Study group | Role | What they receive |
|---|---|---|
| Control Arm | Placebo comparator | 50 mL normal saline solution Receives: Drug: Normal saline solution |
| Thiamine | Experimental | 200 mg thiamine in 50 mL normal saline solution Receives: Drug: Thiamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lactate Levels
Measured: Post-surgery within 1 hour of arrival to the ICU
Secondary outcomes (4)
Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity
PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method. Reported as relative change from before the surgery.
Measured: Post-surgery within 1 hour of arrival to the ICU
Patients With Post-operative Complications
Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection
Measured: Until hospital discharge, limit 60 days
Length of Stay
Duration of intensive care unit stay
Measured: Until hospital discharge, limit 60 days
Mortality
Measured: Until hospital discharge, limit 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2014 (estimated)
- Study startJan 2015
- Primary completionAug 2015
- Study completionAug 2015
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery BypassStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- 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
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- American Heart Association, University of Aarhus
- Responsible party
- Principal investigator, Michael Donnino, Beth Israel Deaconess Medical Center
- Investigators
- Michael W Donnino, M.D., Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02322892
- Sponsor's protocol ID
- 2014P000257
- Status last verified
- Mar 2017
- First submitted
- 14 Dec 2014
- Last updated
- 30 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Andersen LW, Holmberg MJ, Berg KM, Chase M, Cocchi MN, Sulmonte C, Balkema J, MacDonald M, Montissol S, Senthilnathan V, Liu D, Khabbaz K, Lerner A, Novack V, Liu X, Donnino MW. Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial. Crit Care. 2016 Mar 14;20:92. doi: 10.1186/s13054-016-1245-1.
PubMed 27044557
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thiamine as an Adjunctive Therapy in Cardiac Surgery
- ClinicalTrials.gov ID
- NCT02322892
- Acronym / sponsor ID
- 2014P000257
- Keywords
- Thiamine, Vitamin B1, Coronary artery bypass grafting, Cardiac surgery, Lactate, Pyruvate dehydrogenase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- American Heart Association, University of Aarhus
- Study start
- Jan 2015
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 23 Dec 2014 (estimated)
- Results
- Posted 30 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this pilot study is to test the effects of thiamine (vitamin B1) administration before and after major cardiac surgery. Half of patients will receive thiamine and the other half will receive placebo.
The investigators' main hypothesis is that thiamine will improve cellular oxygen consumption and lead to decreased levels of post-operative lactate levels and ultimately improved patient outcomes.
Detailed description
Over 230,000 patients in the United States undergo Coronary Artery Bypass Grafting (CABG) each year. While mortality is relatively low, morbidity remains substantial with a significant risk of prolonged time on mechanical ventilation, prolonged length of hospital and intensive care unit stay and many other complications. CABG causes a profound stress response and significant metabolic alterations occur, including a shift from aerobic to anaerobic metabolism, causing increased levels of pyruvate and lactate. Elevated lactate, a marker of anaerobic metabolism, is a common and significant finding in patients after CABG and is correlated with increased mortality and morbidity.
Aerobic metabolism occurs when pyruvate enters the mitochondria through pyruvate decarboxylation to acetyl-Coenzyme A, facilitated by the enzyme pyruvate dehydrogenase (PDH). Decreased PDH activity may cause a shift toward anaerobic metabolism and play a role in the changes seen in patients undergoing CABG. Thiamine (vitamin B1) is a key co-factor for PDH function and will increase activity even in non-deficient states. The investigators hypothesize that thiamine administration will increase PDH activity in patients undergoing CABG, leading to increased cellular oxygen consumption, as represented by decreased lactate levels after surgery, and ultimately improved clinical outcomes.
In order to test the investigators' hypothesis and to obtain data for a large-scale clinical trial evaluating relevant clinical endpoints, the investigators are conducting a randomized, double-blind, pilot trial of thiamine in high-risk patients undergoing CABG.
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 |
|---|---|---|
| Control Arm | Placebo comparator | Drug: Normal saline solution50 mL normal saline solution |
| Thiamine | Experimental | Drug: Thiamine200 mg thiamine in 50 mL normal saline solution |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult (≥ 21 years)
- Coronary artery bypass grafting (CABG) with or without concomitant valve procedures
- EuroSCORE II > 1.5%
Key exclusion criteria (6 listed)
- Current thiamine supplementation
- Known allergy to thiamine
- Competing indication for thiamine administration as judged by the clinical team (e.g., alcoholic)
- Research-protected populations (pregnant women, prisoners, the intellectually disabled)
- Emergent or salvage CABG (as defined by the Society of Thoracic Surgeons)
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 |
|---|---|---|
| ThiamineAlso: vitamin B1, Thiamin200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) | Drug | Thiamine |
| Normal saline solution50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit) | Drug | Control Arm |
Primary outcome
Lactate Levels
Time frame: Post-surgery within 1 hour of arrival to the ICU
4 secondary outcomes
Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity
Time frame: Post-surgery within 1 hour of arrival to the ICU
Patients With Post-operative Complications
Time frame: Until hospital discharge, limit 60 days
Length of Stay
Time frame: Until hospital discharge, limit 60 days
Mortality
Time frame: Until hospital discharge, limit 60 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27044557Andersen LW, Holmberg MJ, Berg KM, Chase M, Cocchi MN, Sulmonte C, Balkema J, MacDonald M, Montissol S, Senthilnathan V, Liu D, Khabbaz K, Lerner A, Novack V, Liu X, Donnino MW. Thiamine as an adjunctive therapy in cardiac surgery: a randomized, double-blind, placebo-controlled, phase II trial. Crit Care. 2016 Mar 14;20:92. doi: 10.1186/s13054-016-1245-1.
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Coronary Artery Disease, Left Ventricular Systolic Dysfunction
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Thiamine Intervention and Coronary Artery Bypass Grafting
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Preoperative Gastric Ultrasound and Anaesthetic Management in Patients Undergoing Coronary Artery Bypass Grafting
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Coronary Artery Bypass Graft (CABG)
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, M.D. 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 and Normal saline solution in people with Coronary Artery Bypass and Cardiac Surgical Procedures, run by Beth Israel Deaconess Medical Center 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 3 inclusion and 6 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: finished, as of the sponsor's last update on 30 Mar 2017. 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 30 Mar 2017). 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 Levels (time frame: Post-surgery within 1 hour of arrival to the ICU). 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 NCT02322892, which also lists 1 linked publication.
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 30 Mar 2017.