- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03102723
Platelet Inhibition to Target Reperfusion Injury (PITRI)
Platelet Inhibition to Target Reperfusion Injury: The PITRI Trial
Study Overview
Detailed Description
The PITRI proof-of-concept clinical trial will randomise 210 STEMI patients to receive either Cangrelor (single intravenous bolus followed by a 120-minute infusion) or matching normal/saline placebo, initiated prior to PPCI on top of conventional oral dual antiplatelet therapy (Aspirin + Ticagrelor).
The primary endpoint will be acute MI size by cardiac MRI at day 2-7. Secondary endpoints will include incidence and extent of MVO by cardiac MRI; and chronic MI size, left ventricular size and ejection fraction by cardiac MRI at 6 months.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Singapore, Singapore, 768828
- Khoo Teck Puat Hospital
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Singapore, Singapore, 119228
- National University Hospital (NUH)
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Singapore, Singapore, 308433
- Tan Tock Seng Hospital (TTSH)
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Singapore, Singapore, S529889
- Changi General Hospital
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Singapore, Singapore, S544886
- Sengkang General Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria Subjects must meet all of the inclusion criteria to participate in this study.
- Age ≥21 and <80 years of age
STEMI as defined by:
- ≥2 mm ST-segment elevation in 2 or more anterior leads (V1-V4)
- ≥1 mV ST-segment elevation in in 2 or more limb leads (II, III and aVF, I, aVL).
- ST elevation in II, II, aVF less than 1 mm with ST depression in aVL
- Posterior infarction ST depression ≥ 1 mm over either V1, V2, or V3 and ST elevation ≥ 1 mm in either V7, V8 or V9
- ≤6 hours onset of most severe chest pain to time of admission in the Emergency Medicine Department
Exclusion Criteria All subjects meeting any of the exclusion criteria at baseline will be excluded from participation.
- History of previous MI, CVA, TIA or prior CABG surgery
- Known contraindications to cardiac MRI (CMR) such as MRI contraindicated implanted devices, significant claustrophobia, severe allergy to gadolinium chelate contrast, severe renal insufficiency (estimated glomerular filtration rate [eGFR] ≤40 mL/min/1.73 m2)
- Patients with prior therapy before admission within 7 days of anticoagulant (warfarin, phenindione, dabigatran, apixaban and rivaroxaban), glycoprotein 2B3A inhibitor, P2Y12 inhibitor (ticagrelor, prasugrel, clopidogrel, cangrelor) or thrombolytic therapy
Significant co-morbidities:
- Patients with severe hepatic failure (INR>2)
- Cardiac arrest before randomisation
- Cardiogenic shock
- Poor premorbid status (bed bound / wheelchair bound)
- Collapse / comatose / semi-conscious states
Contraindications to Heparinisation or Anti-Platelet Therapy:
- History of Heparin-Induced Thrombocytopenia (HIT)
- Increased bleeding risk (GI bleeding, traumatic head injury)
- Pregnancy
- Contrast allergy
- Patients on strong CYP3A inhibitors or inducers (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole, rifampin, dexamethasone, phenytoin, carbamazepine, and phenobarbital)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cangrelor
Cangrelor (single intravenous bolus followed by a 120-minute infusion) initiated prior to PPCI.
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Other Names:
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Placebo Comparator: Placebo
Matching normal saline placebo (single intravenous bolus followed by a 120-minute infusion) initiated prior to PPCI.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Myocardial infarct size by CMR at Day 2 to 7
Time Frame: 2-7 days
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This will be measured by CMR (mass of late gadolinium enhancement expressed as a percentage of the LV mass).
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2-7 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Microvascular obstruction to calculate myocardial interstitial volume
Time Frame: 2-7 days
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This will be assessed by CMR performed at 2-7 days post-PPCI
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2-7 days
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Myocardial salvage index
Time Frame: 2-7 days
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This will be assessed by cardiac magnetic resonance (CMR) performed at 2-7 days post-PPCI by measuring MI size and the area at risk
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2-7 days
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Angiographic markers of successful reperfusion
Time Frame: 2 to 3 hours
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ST-segment resolution 90 min post-PPCI, TIMI flow and frame-count post-PPCI, and TIMI blush grade
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2 to 3 hours
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Myocardial infarct size by CMR at 6 months
Time Frame: 6 months
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This will be measured by Cardiac MRI 6 months post-PPCI
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6 months
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Post-MI LV remodeling by measuring LV ejection fraction and indexed LV end systolic and diastolic volumes and mass
Time Frame: 6 months
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This will be assessed by CMR by measuring LV ejection fraction and indexed LV end systolic and diastolic volumes and mass.
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6 months
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Platelet function testing
Time Frame: 2 hours
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Serial platelet function testing will be performed with VerifyNow in a subset of 70 patients.
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2 hours
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MACCE at 30 days, at 6 months, at 12 months, at 24 months, at 5 years and at 10 years
Time Frame: 6 months
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This will include all-cause death, hospitalisation for heart failure (HHF), stent thrombosis, ischemia-induced coronary revascularisation, re-infarction, and stroke.
This data will be collected by telephone and reviewing medical notes at 30 days and at the time of the outpatient 6 month cardiac MR scan.
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6 months
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Incidence of definite stent thrombosis at 48 hours
Time Frame: 48 hours
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This will be defined according to the criteria of the Academic Research Consortium, which was assessed, with group assignments concealed, at an angiographic core laboratory (Cardiovascular Research Foundation).
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48 hours
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Quality of life questionnaire
Time Frame: 6 months
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The EuroQol EQ-5D Health-Related Quality of Life (EUROQOL) questionnaire (www.euroqol.org)
will be used to assess patient quality of life post-CABG with or without valve surgery, at baseline (1 day post-PPCI), 30 days (by telephone), and 6 months (at time of outpatient CMR scan).
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6 months
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6-Minute Walk Test (6MWT)
Time Frame: 6 months
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Functional capacity of patients will be measured using the 6-Minute Walk Test
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6 months
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Subjective questionnaire
Time Frame: 6 months
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Subjective questionnaire relating to symptoms post angioplasty and physical activities will be assess at 30±7 days (by telephone), and at 6±1 months (at time of the outpatient CMR scan).
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6 months
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ALDH2 substudy
Time Frame: 6 months
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A saliva sample will be collected from a sub-group of subjects for determination of their ALDH2 genotype.
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6 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Derek John Hausenloy, National Heart Centre Singapore
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Postoperative Complications
- Reperfusion Injury
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Platelet Aggregation Inhibitors
- Purinergic P2Y Receptor Antagonists
- Purinergic P2 Receptor Antagonists
- Purinergic Antagonists
- Purinergic Agents
- Cangrelor
Other Study ID Numbers
- PITRI-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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