Thiamine as an Adjunctive Therapy in Cardiac Surgery

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 2015

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.

Interventions

  • Drug: Thiamine
    • 200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)
  • Drug: Normal saline solution
    • 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)

Arms, Groups and Cohorts

  • Placebo Comparator: Control Arm
    • 50 mL normal saline solution
  • Experimental: Thiamine
    • 200 mg thiamine in 50 mL normal saline solution

Clinical Trial Outcome Measures

Primary Measures

  • Lactate Levels
    • Time Frame: Post-surgery within 1 hour of arrival to the ICU

Secondary Measures

  • Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity
    • Time Frame: 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
    • Time Frame: Until hospital discharge, limit 60 days
    • Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection
  • Length of Stay
    • Time Frame: Until hospital discharge, limit 60 days
    • Duration of intensive care unit stay
  • Mortality
    • Time Frame: Until hospital discharge, limit 60 days

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: 21 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Beth Israel Deaconess Medical Center
  • Collaborator
    • American Heart Association
  • Provider of Information About this Clinical Study
    • Principal Investigator: Michael Donnino, M.D. – Beth Israel Deaconess Medical Center
  • Overall Official(s)
    • Michael W Donnino, M.D., Principal Investigator, Beth Israel Deaconess Medical Center

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