Thiamine as an Adjunctive Therapy in Cardiac Surgery

Study Overview
=================
Brief 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. 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.

Official Title
-----------------
Thiamine as an Adjunctive Therapy in Cardiac Surgery

Conditions
-----------------
Coronary Artery Bypass, Cardiac Surgical Procedures

Intervention / Treatment
-----------------
* Drug: Thiamine
* Drug: Normal saline solution


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult (≥ 21 years) Coronary artery bypass grafting (CABG) with or without concomitant valve procedures EuroSCORE II > 1.5% Exclusion Criteria: 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)

Ages Eligible for Study
-----------------
Minimum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control Arm<br>50 mL normal saline solution | Drug: Normal saline solution<br>* 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)<br>|
| Experimental: Thiamine<br>200 mg thiamine in 50 mL normal saline solution | Drug: Thiamine<br>* 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)<br>* Other names: Thiamin;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lactate Levels |  | Post-surgery within 1 hour of arrival to the ICU | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | Until hospital discharge, limit 60 days | 
| Length of Stay | Duration of intensive care unit stay | Until hospital discharge, limit 60 days | 
| Mortality |  | Until hospital discharge, limit 60 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Thiamine, Vitamin B1, Coronary artery bypass grafting, Cardiac surgery, Lactate, Pyruvate dehydrogenase