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

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ClinicalTrials.gov Identifier: NCT00858936
Recruitment Status : Terminated (Study Terminated - Company decision)
First Posted : March 10, 2009
Last Update Posted : October 19, 2016
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Coronary Artery Bypass Surgery Drug: IK-1001 Drug: Normal Saline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : May 2009
Actual Primary Completion Date : April 2010
Actual Study Completion Date : April 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: IK-1001
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
Drug: IK-1001
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

Placebo Comparator: Normal Saline
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
Drug: Normal Saline
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 Measures :
  1. Cardiac Troponin T [ Time Frame: Day 1 through Day 4 ]

Secondary Outcome Measures :
  1. Mortality [ Time Frame: Study duration ]
  2. 12-Lead ECG [ Time Frame: Periodically through study duration ]
  3. Urinalysis [ Time Frame: Screening, and 6 month ]
  4. Echocardiography [ Time Frame: Screening, 3 month and 6 month ]
  5. Blood Draws [ Time Frame: Study duration ]
  6. Vital Signs [ Time Frame: Study duration ]
  7. MRI [ Time Frame: Screening, 1 month ]
  8. Adverse events [ Time Frame: Study duration ]
  9. Serum levels of CK-MB [ Time Frame: Day 1 through Day 4 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00858936

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Australia, South Australia
Ashford Hospital
Ashford, South Australia, Australia, 5035
Flinder Medical Center
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Austin Hospital
Heidelberg, Victoria, Australia, 3084
Alfred Hospital
Melbourne, Victoria, Australia, 3004
St. Vincents Hospital
Melbourne, Victoria, Australia
Canada, Manitoba
Boniface General Hospital
Winnepeg, Manitoba, Canada, R2H 2A6
Canada, Quebec
Royal Victoria Hospital - MUHC
Montreal, Quebec, Canada, H3A 1A1
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
Sponsors and Collaborators
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Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT00858936    
Other Study ID Numbers: S201
First Posted: March 10, 2009    Key Record Dates
Last Update Posted: October 19, 2016
Last Verified: October 2016
Keywords provided by Mallinckrodt:
CABG(coronary artery bypass graft)
Heart surgery
Heart damage
Additional relevant MeSH terms:
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Pathologic Processes