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

18 oktober 2016 bijgewerkt door: Mallinckrodt

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.

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.

Studie Overzicht

Toestand

Beëindigd

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

6

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Australië
    • South Australia
      • Ashford, South Australia, Australië, 5035
        • Ashford Hospital
      • Bedford Park, South Australia, Australië, 5042
        • Flinder Medical Center
    • Victoria
      • Heidelberg, Victoria, Australië, 3084
        • Austin Hospital
      • Melbourne, Victoria, Australië, 3004
        • Alfred Hospital
      • Melbourne, Victoria, Australië
        • St. Vincents Hospital
  • Canada
    • Manitoba
      • Winnepeg, Manitoba, Canada, R2H 2A6
        • Boniface General Hospital
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H3A 1A1
        • Royal Victoria Hospital - MUHC

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 85 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Verdrievoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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
Geneesmiddel: 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-vergelijker: 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
Geneesmiddel: 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

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Cardiac Troponin T
Tijdsspanne: Day 1 through Day 4
Day 1 through Day 4

Secundaire uitkomstmaten

Uitkomstmaat
Tijdsspanne
Vitale functies
Tijdsspanne: Studie duur
Studie duur
Sterfte
Tijdsspanne: Studie duur
Studie duur
12-Lead ECG
Tijdsspanne: Periodically through study duration
Periodically through study duration
Urinalysis
Tijdsspanne: Screening, and 6 month
Screening, and 6 month
Echocardiography
Tijdsspanne: Screening, 3 month and 6 month
Screening, 3 month and 6 month
Blood Draws
Tijdsspanne: Study duration
Study duration
MRI
Tijdsspanne: Screening, 1 month
Screening, 1 month
Adverse events
Tijdsspanne: Study duration
Study duration
Serum levels of CK-MB
Tijdsspanne: Day 1 through Day 4
Day 1 through Day 4

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Mallinckrodt

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 mei 2009

Primaire voltooiing (Werkelijk)

1 april 2010

Studie voltooiing (Werkelijk)

1 april 2010

Studieregistratiedata

Eerst ingediend

9 maart 2009

Eerst ingediend dat voldeed aan de QC-criteria

9 maart 2009

Eerst geplaatst (Schatting)

10 maart 2009

Updates van studierecords

Laatste update geplaatst (Schatting)

19 oktober 2016

Laatste update ingediend die voldeed aan QC-criteria

18 oktober 2016

Laatst geverifieerd

1 oktober 2016

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • S201

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Klinische onderzoeken op Kroonslagader bijpas operatie

Klinische onderzoeken op IK-1001

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Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

CROs by country

CROs in Taiwan

Voorwaarden

Zeldzame ziekten

Geneesmiddelinterventies

Voedingssupplementen

Sponsor / medewerkers

Locaties

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