Thiamine as an Adjunctive Therapy in Cardiac Surgery

NCT ID: NCT02322892

Last Updated: 2017-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2015-08-31

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.

Conditions

Coronary Artery Bypass; Cardiac Surgical Procedures

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Control Arm

50 mL normal saline solution

Group Type: PLACEBO_COMPARATOR

Normal saline solution

Intervention Type: DRUG

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

Thiamine

200 mg thiamine in 50 mL normal saline solution

Group Type: EXPERIMENTAL

Thiamine

Intervention Type: DRUG

200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)

Interventions

Thiamine

200 mg thiamine in 50 mL normal saline once immediately before surgery and once immediately after (at arrival in the intensive care unit)

Intervention Type: DRUG

Normal saline solution

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

Intervention Type: DRUG

Other Intervention Names

vitamin B1; Thiamin

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)

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Heart Association

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Michael Donnino

M.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael W Donnino, M.D.

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27044557 (View on PubMed)

Other Identifiers

2014P000257

Identifier Type: -

Identifier Source: org_study_id