Clinical trial NCT02322892: Thiamine as an Adjunctive Therapy in Cardiac Surgery
Official title: Thiamine as an Adjunctive Therapy in Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Bypass
Cardiac Surgical Procedures
Keywords: Thiamine
Vitamin B1
Coronary artery bypass grafting
Cardiac surgery
Lactate
Pyruvate dehydrogenase
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
name: University of Aarhus
First posted: 2014-12-23
Enrollment: 64
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Lactate Levels
timeFrame: Post-surgery within 1 hour of arrival to the ICU
Secondary outcomes:
measure: Percentage Change From Baseline in Pyruvate Dehydrogenase (PDH) Enzyme Activity
timeFrame: Post-surgery within 1 hour of arrival to the ICU
measure: Patients With Post-operative Complications
timeFrame: Until hospital discharge, limit 60 days
measure: Length of Stay
timeFrame: Until hospital discharge, limit 60 days
measure: Mortality
timeFrame: Until hospital discharge, limit 60 days
Other outcomes:
measure: Lactate Levels
timeFrame: Six hours after end of surgery surgery
measure: Pyruvate Dehydrogenase (PDH) Enzyme Activity
timeFrame: Six hours after end of surgery surgery
measure: Time on Mechanical Ventilation
timeFrame: Limit 60 days
measure: Time on Vasopressors
timeFrame: Limit 60 days
measure: Global Oxygen Consumption (VO2)
timeFrame: From arrival to ICU to extubation, limit 6 hours
measure: Cellular Oxygen Consumption
timeFrame: Post-surgery within 1 hour of arrival to the ICU
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Michael W Donnino, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.