Thiamine as an Adjunctive Therapy in Cardiac Surgery

Coronary Artery Bypass Clinical Trial

Official title:

Thiamine as an Adjunctive Therapy in Cardiac Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02322892
• Other study ID #: 2014P-000257
• Status: Completed
• Phase: Phase 2
• First received: December 14, 2014
• Last updated: September 3, 2015
• Start date: January 2015
• Est. completion date: August 2015

Study information

• Verified date: September 2015
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical 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.

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.

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 information / eligibility

• Status: Completed
• Enrollment: 64
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Surgical Procedures
• Coronary Artery Bypass

Intervention

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)
• Normal saline solution
50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	American Heart Association, University of Aarhus

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Lactate levels		Six hours after end of surgery surgery	No
Other	Pyruvate dehydrogenase (PDH) enzyme activity	PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method	Six hours after end of surgery surgery	No
Other	Time on mechanical ventilation		Limit 60 days	No
Other	Time on vasopressors		Limit 60 days	No
Other	Global oxygen consumption (VO2)	VO2 will be measured with a Compact Anesthesia monitor	From arrival to ICU to extubation, limit 6 hours	No
Other	Cellular oxygen consumption	Cellular (peripheral blood mononuclear cells) oxygen consumption measured with the XFe24 Extracellular Flux Analyzers	Post-surgery within 1 hour of arrival to the ICU	No
Primary	Lactate levels		Post-surgery within 1 hour of arrival to the ICU	No
Secondary	Pyruvate dehydrogenase (PDH) enzyme activity	PDH activity will be measured in isolated peripheral blood mononuclear cells using a novel immunocapture and microplate-based method	Post-surgery within 1 hour of arrival to the ICU	No
Secondary	Post-operative complications	Atrial fibrillation, delirium, renal failure, stroke, myocardial infarction, acute respiratory distress syndrome, infection	Until hospital discharge, limit 60 days	No
Secondary	Length of stay	Duration of intensive care unit and hospital stay	Until hospital discharge, limit 60 days	No
Secondary	Mortality		Until hospital discharge, limit 60 days	No