Reduction of Ischemia-Reperfusion Mediated Cardiac Injury in Subjects Undergoing Coronary Artery Bypass Graft Surgery

Coronary Artery Bypass Surgery Clinical Trial

Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of IK-1001 to Evaluate Safety, Pharmacokinetics and Proof-of-concept Efficacy for Reduction of Ischemia-Reperfusion Mediated Cardiac Injury in Subjects Undergoing Coronary Artery Bypass Graft(CABG)Surgery

Status Terminated

Clinical Trial Summary

This clinical trial will investigate the safety and effectiveness of IK-1001 (the liquid form of sodium sulfide) when used in Coronary Artery Bypass Graft (CABG) patients to potentially reduce the damage done to the heart during surgery.

This study has 2 parts. Part 1 will first test 36 subjects at different doses (amount) of the study drug. There will be 6 different groups of 6 subjects each that will receive the study drug or a placebo. A placebo is a substance that will be prepared to look like the study drug but will contain no active ingredients. In Part 1, five subjects from each group will receive study drug (IK-1001) and one will receive a placebo. This first part of this study is also a dose (amount) escalation. This means that each group will be receiving a different dose of the study drug. The first group will receive the lowest dose, the second group will receive a slightly higher dose, and the third group a slightly higher dose until all six groups has been tested. You can not choose which group you will be in but prior to starting each new dose level, the data (information) from the previous dose level will have been reviewed by a group of qualified individuals to determine if it is safe to proceed to the next highest dose level.

Part 2 will expand the study and will treat at least 158 (and up to 632) more subjects at a dose level that has been deemed safe from information collected from Part 1. Subjects in Part 2 of the study will have a 1 in 2 (50%) chance of receiving the study drug or placebo. Whether the subject gets study drug or the placebo will be randomly assigned (like the toss of a coin).

The study drug or placebo will be given as an intravenous infusion (into the vein) for six hours while the subject is having their CABG surgery.

The subjects will be followed up for 6 months after their CABG surgery.

Clinical Trial Description

This is a phase 2, randomized, double-blind, placebo-controlled, multicenter, dose escalation and dose-expansion, study that will evaluate safety, PK, and POC-efficacy of IK-1001 in subjects undergoing on pump CABG surgery who are at an increased risk for I/R mediated tissue damage.

Study subjects will undergo planned CABG surgery with cardiopulmonary bypass. The study will be conducted in two parts. Part 1 of the study will involve the dose escalation to evaluate safety, PK, and preliminary efficacy of IK-1001. Up to 36 eligible subjects will be enrolled into the Part 1 portion and randomized to receive either placebo (n = 6) or IK-1001 (n = 30) at 6 dose escalating levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours.

The study drug administration will begin in the operating room after the induction of anesthesia and prior to the surgical incision.

After safety, efficacy, and PK data have been evaluated in Part 1, the optimum dose will be determined and this dose will be expanded in Part 2. Initially up to 158 eligible subjects will be randomized to receive either IK-1001 or placebo at a 1:1 ratio. Part 2 aims to further establish safety, PK as well as POC efficacy.

In the event that none of the 4 primary endpoints reach at least a 15% decline as compared with placebo, the Sponsor may decide to amend the protocol to explore a higher dose. After 6 subjects have been dosed at this higher dose level, the data will be reviewed by the Sponsor or designee for safety and PK and the remaining subjects will then be enrolled. If the safety and PK data are favorable, the study will be completed at this higher dose level. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Bypass Surgery
• Ischemia

• NCT number: NCT00858936
• Study type: Interventional
• Source: Mallinckrodt
• Status: Terminated
• Phase: Phase 2
• Start date: May 2009
• Completion date: April 2010