Platelet Inhibition to Target Reperfusion Injury

Phase 2

• Conditions: STEMI
• Interventions: Drug: Cangrelor

• Registration Number: NCT03102723
• Lead Sponsor: National Heart Centre Singapore

Brief Summary

There remains a clinical need to improve health outcomes in patients with ischemic heart disease (IHD) the leading cause of death and disability in Singapore and worldwide. One neglected therapeutic target is 'myocardial reperfusion injury' in ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention (PPCI). This results in microvascular obstruction (MVO) and cardiomyocyte death and contributes upto 50% of the final myocardial infarct (MI) size. Cangrelor, a potent intravenous platelet P2Y12 inhibitor with rapid onset and offset of action, has been demonstrated in experimental animal studies to reduce MI size when administered prior to reperfusion. Whether Cangrelor given together with Ticagrelor would be more effective at reducing MI size in STEMI patients treated by PPCI is not known and is investigated in the Platelet Inhibition to Target Reperfusion Injury (PITRI) trial.

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 Timeline

• Study First Submitted: 2017-01-05
• Study First Submitted QC: 2017-03-30
• Study First Posted: 2017-04-06
• Study Start: 2017-10-01
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-26
• Primary Completion: 2022-12
• Study Completion: 2022-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cangrelor	Cangrelor	Cangrelor (single intravenous bolus followed by a 120-minute infusion) initiated prior to PPCI.
Placebo	Cangrelor	Matching normal saline placebo (single intravenous bolus followed by a 120-minute infusion) initiated prior to PPCI.

Primary Outcome Measures

Name	Time	Method
Myocardial infarct size by CMR at Day 2 to 7	2-7 days	This will be measured by CMR (mass of late gadolinium enhancement expressed as a percentage of the LV mass).

Secondary Outcome Measures

Name	Time	Method
Myocardial infarct size by CMR at 6 months	6 months	This will be measured by Cardiac MRI 6 months post-PPCI
Post-MI LV remodeling by measuring LV ejection fraction and indexed LV end systolic and diastolic volumes and mass	6 months	This will be assessed by CMR by measuring LV ejection fraction and indexed LV end systolic and diastolic volumes and mass.
Myocardial salvage index	2-7 days	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
Angiographic markers of successful reperfusion	2 to 3 hours	ST-segment resolution 90 min post-PPCI, TIMI flow and frame-count post-PPCI, and TIMI blush grade
Microvascular obstruction to calculate myocardial interstitial volume	2-7 days	This will be assessed by CMR performed at 2-7 days post-PPCI
MACCE at 30 days, at 6 months, at 12 months, at 24 months, at 5 years and at 10 years	6 months	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.
Subjective questionnaire	6 months	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).
Platelet function testing	2 hours	Serial platelet function testing will be performed with VerifyNow in a subset of 70 patients.
Incidence of definite stent thrombosis at 48 hours	48 hours	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).
Quality of life questionnaire	6 months	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).
6-Minute Walk Test (6MWT)	6 months	Functional capacity of patients will be measured using the 6-Minute Walk Test
ALDH2 substudy	6 months	A saliva sample will be collected from a sub-group of subjects for determination of their ALDH2 genotype.

Trial Locations

Locations (5)

National University Hospital (NUH); 🇸🇬 Singapore, Singapore

Khoo Teck Puat Hospital; 🇸🇬 Singapore, Singapore

Changi General Hospital; 🇸🇬 Singapore, Singapore

SengKang General Hospital; 🇸🇬 Singapore, Singapore

Tan Tock Seng Hospital (TTSH); 🇸🇬 Singapore, Singapore