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

Primary Purpose

Coronary Artery Bypass Surgery

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IK-1001
Normal Saline
Sponsored by
Mallinckrodt
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Bypass Surgery focused on measuring CABG(coronary artery bypass graft), Ischemia, Heart surgery, Heart damage

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subjects must be 18 to 85 years of age
  2. Subject is scheduled to undergo CABG surgery with cardiopulmonary bypass

  3. Subjects at an increased risk for I/R mediated tissue damage: defined as subjects with ≥ 30% but ≤ 50% ejection fraction (as measured by echocardiography within 14 days of study enrollment) or who fulfill at least two of the following criteria:

    • Current or recent smoker (within last 6 months prior to screening)
    • Female
    • Diabetes mellitus (a history of diabetes, regardless of duration of disease or need for anti-diabetic agents)
    • History of non-disabling stroke, TIA, carotid endarterectomy
    • Re- CABG (H/O previous CABG surgery, on or off-pump)
    • Peripheral artery surgery or angioplasty
    • Recent MI (≥ 48 hours and ≤ 6 weeks before surgery, non STEMI and STEMI infarcts as documented in the medical records of the subject)
    • History of congestive heart failure (NYHA CHF Class III or IV)
    • Renal dysfunction: creatinine clearance ≥ 30mL/min but < 60mL/min calculated using Crockroft and Gault formula: Creatinine clearance (mL/min) = (140 - age) x weight (kg) (x 0.85 for females) (72 x serum creatinine)
    • Asymptomatic stenosis (≥ 50%) in ≥ 1 carotid artery
    • Age > 65 years

Exclusion Criteria:

  1. Known sulfite allergy or sulphur drug allergy
  2. Subjects who have received treatment for asthma within the past 12 months
  3. Myocardial infarction occurring < 48 hours prior to surgery
  4. Current cardiogenic shock, acute left ventricular rupture, ventricular septal rupture, or papillary muscle rupture
  5. History of prior disabling stroke
  6. Clinically relevant liver disease (defined as serum transaminases ≥ 3 x upper limit of normal for local laboratory)
  7. Poorly controlled diabetes mellitus (defined as HbA1c > 9.0%)
  8. Planned concomitant cardiac valve or other surgery at time of CABG
  9. Planned use of thiopental during anesthesia for CABG surgery
  10. All females of child bearing potential (defined as having menses without an alternative medical cause during the last 12 months). Women who are pregnant (defined as a positive serum pregnancy test), breast-feeding or lactating are also excluded.
  11. Ongoing alcohol or drug abuse
  12. Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study
  13. Subject has participated in another investigational drug or device study within 30 days prior to enrollment to the study.

Sites / Locations

  • Ashford Hospital
  • Flinder Medical Center
  • Austin Hospital
  • Alfred Hospital
  • St. Vincents Hospital
  • Boniface General Hospital
  • Royal Victoria Hospital - MUHC
  • Jewish General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IK-1001

Normal Saline

Arm Description

6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours

6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours

Outcomes

Primary Outcome Measures

Cardiac Troponin T

Secondary Outcome Measures

Mortality
12-Lead ECG
Urinalysis
Echocardiography
Blood Draws
Vital Signs
MRI
Adverse events
Serum levels of CK-MB

Full Information

First Posted
March 9, 2009
Last Updated
October 18, 2016
Sponsor
Mallinckrodt
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1. Study Identification

Unique Protocol Identification Number
NCT00858936
Brief Title
Reduction of Ischemia-Reperfusion Mediated Cardiac Injury in Subjects Undergoing Coronary Artery Bypass Graft Surgery
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2016
Overall Recruitment Status
Terminated
Why Stopped
Study Terminated - Company decision
Study Start Date
May 2009 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mallinckrodt

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Bypass Surgery
Keywords
CABG(coronary artery bypass graft), Ischemia, Heart surgery, Heart damage

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IK-1001
Arm Type
Experimental
Arm Description
6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours
Arm Title
Normal Saline
Arm Type
Placebo Comparator
Arm Description
6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours
Intervention Type
Drug
Intervention Name(s)
IK-1001
Intervention Description
6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Intervention Description
6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours
Primary Outcome Measure Information:
Title
Cardiac Troponin T
Time Frame
Day 1 through Day 4
Secondary Outcome Measure Information:
Title
Mortality
Time Frame
Study duration
Title
12-Lead ECG
Time Frame
Periodically through study duration
Title
Urinalysis
Time Frame
Screening, and 6 month
Title
Echocardiography
Time Frame
Screening, 3 month and 6 month
Title
Blood Draws
Time Frame
Study duration
Title
Vital Signs
Time Frame
Study duration
Title
MRI
Time Frame
Screening, 1 month
Title
Adverse events
Time Frame
Study duration
Title
Serum levels of CK-MB
Time Frame
Day 1 through Day 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must be 18 to 85 years of age Subject is scheduled to undergo CABG surgery with cardiopulmonary bypass Subjects at an increased risk for I/R mediated tissue damage: defined as subjects with ≥ 30% but ≤ 50% ejection fraction (as measured by echocardiography within 14 days of study enrollment) or who fulfill at least two of the following criteria: Current or recent smoker (within last 6 months prior to screening) Female Diabetes mellitus (a history of diabetes, regardless of duration of disease or need for anti-diabetic agents) History of non-disabling stroke, TIA, carotid endarterectomy Re- CABG (H/O previous CABG surgery, on or off-pump) Peripheral artery surgery or angioplasty Recent MI (≥ 48 hours and ≤ 6 weeks before surgery, non STEMI and STEMI infarcts as documented in the medical records of the subject) History of congestive heart failure (NYHA CHF Class III or IV) Renal dysfunction: creatinine clearance ≥ 30mL/min but < 60mL/min calculated using Crockroft and Gault formula: Creatinine clearance (mL/min) = (140 - age) x weight (kg) (x 0.85 for females) (72 x serum creatinine) Asymptomatic stenosis (≥ 50%) in ≥ 1 carotid artery Age > 65 years Exclusion Criteria: Known sulfite allergy or sulphur drug allergy Subjects who have received treatment for asthma within the past 12 months Myocardial infarction occurring < 48 hours prior to surgery Current cardiogenic shock, acute left ventricular rupture, ventricular septal rupture, or papillary muscle rupture History of prior disabling stroke Clinically relevant liver disease (defined as serum transaminases ≥ 3 x upper limit of normal for local laboratory) Poorly controlled diabetes mellitus (defined as HbA1c > 9.0%) Planned concomitant cardiac valve or other surgery at time of CABG Planned use of thiopental during anesthesia for CABG surgery All females of child bearing potential (defined as having menses without an alternative medical cause during the last 12 months). Women who are pregnant (defined as a positive serum pregnancy test), breast-feeding or lactating are also excluded. Ongoing alcohol or drug abuse Any underlying medical or psychiatric condition that, in the opinion of the Investigator, makes the subject an unsuitable candidate for the study Subject has participated in another investigational drug or device study within 30 days prior to enrollment to the study.
Facility Information:
Facility Name
Ashford Hospital
City
Ashford
State/Province
South Australia
ZIP/Postal Code
5035
Country
Australia
Facility Name
Flinder Medical Center
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
Austin Hospital
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
St. Vincents Hospital
City
Melbourne
State/Province
Victoria
Country
Australia
Facility Name
Boniface General Hospital
City
Winnepeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
Royal Victoria Hospital - MUHC
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A 1A1
Country
Canada
Facility Name
Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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