Coronary Artery Bypass SurgeryPhase 2NCT00858936
Reduction of Ischemia-Reperfusion Mediated Cardiac Injury in Subjects Undergoing Coronary Artery Bypass Graft Surgery
A Phase 2 study testing IK-1001 and Normal Saline in people with Coronary Artery Bypass Surgery, run by Mallinckrodt at 8 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Coronary Artery Bypass Surgery
- What is being tested?
- IK-1001 and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 8 sitesin 2 countries
- Study dates
- May 2009to Apr 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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)
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- 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.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Australia5 sites
Ashford Hospital
Ashford, South Australia, 5035
Flinder Medical Center
Bedford Park, South Australia, 5042
Austin Hospital
Heidelberg, Victoria, 3084
Alfred Hospital
Melbourne, Victoria, 3004
St. Vincents Hospital
Melbourne, Victoria
Canada3 sites
Royal Victoria Hospital - MUHC
Montreal, Quebec, H3A 1A1
Jewish General Hospital
Montreal, Quebec, H3T 1E2
Boniface General Hospital
Winnepeg, Manitoba, R2H 2A6
About this study
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
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.
Read more
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.
Read the 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.
- Conditions
- Coronary Artery Bypass Surgery
- Being tested
- IK-1001, Normal Saline
- Keywords
- CABG(coronary artery bypass graft), Ischemia, Heart surgery, Heart damage
- Medical subject headings
- Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IK-1001Drug
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
Normal SalineDrug
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
| Study group | Role | What they receive |
|---|---|---|
| IK-1001 | Experimental | 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 Receives: Drug: IK-1001 |
| Normal Saline | Placebo comparator | 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 Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac Troponin T
Measured: Day 1 through Day 4
Secondary outcomes (9)
Mortality
Measured: Study duration
12-Lead ECG
Measured: Periodically through study duration
Urinalysis
Measured: Screening, and 6 month
Echocardiography
Measured: Screening, 3 month and 6 month
Blood Draws
Measured: Study duration
Vital Signs
Measured: Study duration
MRI
Measured: Screening, 1 month
Adverse events
Measured: Study duration
Serum levels of CK-MB
Measured: Day 1 through Day 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2009 (estimated)
- Study startMay 2009
- Primary completionApr 2010
- Study completionApr 2010
Why it stopped: Study Terminated - Company decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Coronary Artery Bypass SurgeryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mallinckrodt
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00858936
- Sponsor's protocol ID
- S201
- Status last verified
- Oct 2016
- First submitted
- 9 Mar 2009
- Last updated
- 19 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00858936
- Acronym / sponsor ID
- S201
- Conditions
- Coronary Artery Bypass Surgery
- Keywords
- CABG(coronary artery bypass graft), Ischemia, Heart surgery, Heart damage
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study Terminated - Company decision
- Enrolment
- 6 participants (actual)
- Lead sponsor
- MallinckrodtIndustry (pharma, biotech, devices)
- Study start
- May 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 10 Mar 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IK-1001 | Experimental | Drug: IK-10016 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours |
| Normal Saline | Placebo comparator | Drug: Normal Saline6 escalating dose levels of 0.2, 0.5, 0.75, 1.0, 1.25, and 1.5 mg/kg/hr infusion for 6 hours |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IK-10016 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 |
| Normal Saline6 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 |
Primary outcome
Cardiac Troponin T
Time frame: Day 1 through Day 4
9 secondary outcomes
Mortality
Time frame: Study duration
12-Lead ECG
Time frame: Periodically through study duration
Urinalysis
Time frame: Screening, and 6 month
Echocardiography
Time frame: Screening, 3 month and 6 month
Blood Draws
Time frame: Study duration
Vital Signs
Time frame: Study duration
MRI
Time frame: Screening, 1 month
Adverse events
Time frame: Study duration
Serum levels of CK-MB
Time frame: Day 1 through Day 4
Results and safety
The study was stopped early (reason given: Study Terminated - Company decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2016.
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Coronary Artery Bypass Graft (CABG)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IK-1001 and Normal Saline in people with Coronary Artery Bypass Surgery, run by Mallinckrodt at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Australia, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study Terminated - Company decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac Troponin T (time frame: Day 1 through Day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2016.