STEMI
Conditions
Keywords
STEMI, primary percutaneous coronary intervention (PPCI), cangrelor, reperfusion
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.
Interventions
DRUGCangrelor
1. Cangrelor treatment: IV Cangrelor as a single IV bolus (30 μg/kg) followed by an infusion (4 μg/kg/min) of at least 120 minutes duration or until PPCI procedure has ended (whichever is longer) - this will be initiated prior to PPCI. This dosing regimen is identical to that used in the CHAMPION trials. Or 2. Placebo control: IV normal saline as a single IV bolus followed by an infusion of at least 120 minutes duration or until PPCI procedure has ended (whichever is longer) - this will be initiated prior to PPCI.
Sponsors
Tan Tock Seng Hospital
National University Hospital, Singapore
Khoo Teck Puat Hospital
Changi General Hospital
Sengkang General Hospital
National Heart Centre Singapore
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet all of the inclusion criteria to participate in this study. 1. Age ≥21 and \<80 years of age 2. 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 3. ≤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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| Platelet function testing | 2 hours | Serial platelet function testing will be performed with VerifyNow in a subset of 70 patients. |
| Microvascular obstruction to calculate myocardial interstitial volume | 2-7 days | This will be assessed by CMR performed at 2-7 days post-PPCI |
| 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 |
| 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). |
| ALDH2 substudy | 6 months | A saliva sample will be collected from a sub-group of subjects for determination of their ALDH2 genotype. |
| 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. |
Countries
Singapore
Outcome results
None listed