Thiamine as an Adjunctive Therapy in Cardiac Surgery

Phase 2

Completed

Conditions: Coronary Artery Bypass
Cardiac Surgical Procedures

Interventions: Drug: Normal saline solution
Drug: Thiamine

Registration Number: NCT02322892

Lead Sponsor: Beth Israel Deaconess Medical Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 64

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Arm	Normal saline solution	50 mL normal saline solution
Thiamine	Thiamine	200 mg thiamine in 50 mL normal saline solution

Primary Outcome Measures

Name	Time	Method
Lactate Levels	Post-surgery within 1 hour of arrival to the ICU

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity	Post-surgery within 1 hour of arrival to the ICU	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.
Patients With Post-operative Complications	Until hospital discharge, limit 60 days	Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection
Mortality	Until hospital discharge, limit 60 days
Length of Stay	Until hospital discharge, limit 60 days	Duration of intensive care unit stay