Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00858936




Registration number
NCT00858936
Ethics application status
Date submitted
9/03/2009
Date registered
10/03/2009
Date last updated
19/10/2016

Titles & IDs
Public title
Reduction of Ischemia-Reperfusion Mediated Cardiac Injury in Subjects Undergoing Coronary Artery Bypass Graft Surgery
Scientific 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
Secondary ID [1] 0 0
S201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Coronary Artery Bypass Surgery 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IK-1001
Treatment: Drugs - Normal Saline

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

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


Treatment: Drugs: 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

Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cardiac Troponin T
Timepoint [1] 0 0
Day 1 through Day 4
Secondary outcome [1] 0 0
Mortality
Timepoint [1] 0 0
Study duration
Secondary outcome [2] 0 0
12-Lead ECG
Timepoint [2] 0 0
Periodically through study duration
Secondary outcome [3] 0 0
Urinalysis
Timepoint [3] 0 0
Screening, and 6 month
Secondary outcome [4] 0 0
Echocardiography
Timepoint [4] 0 0
Screening, 3 month and 6 month
Secondary outcome [5] 0 0
Blood Draws
Timepoint [5] 0 0
Study duration
Secondary outcome [6] 0 0
Vital Signs
Timepoint [6] 0 0
Study duration
Secondary outcome [7] 0 0
MRI
Timepoint [7] 0 0
Screening, 1 month
Secondary outcome [8] 0 0
Adverse events
Timepoint [8] 0 0
Study duration
Secondary outcome [9] 0 0
Serum levels of CK-MB
Timepoint [9] 0 0
Day 1 through Day 4

Eligibility
Key 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
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2010
Sample size
Target
Accrual to date
Final
6
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
Ashford Hospital - Ashford
Recruitment hospital [2] 0 0
Flinder Medical Center - Bedford Park
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Alfred Hospital - Melbourne
Recruitment hospital [5] 0 0
St. Vincents Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
5035 - Ashford
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Manitoba
Country [2] 0 0
Canada
State/province [2] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mallinckrodt
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00858936
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00858936