Platelet Inhibition to Target Reperfusion Injury

NCT ID: NCT03102723

Last Updated: 2022-04-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 228 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-01
• Study Completion Date: 2022-12-31

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.

Conditions

STEMI

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Cangrelor

Cangrelor (single intravenous bolus followed by a 120-minute infusion) initiated prior to PPCI.

Group Type: EXPERIMENTAL

Cangrelor

Intervention Type: DRUG

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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Cangrelor

Intervention Type: DRUG

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.

Interventions

Cangrelor

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.

Intervention Type: DRUG

Other Intervention Names

Kengreal

Eligibility Criteria

Inclusion Criteria

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

1. History of previous MI, CVA, TIA or prior CABG surgery

2. 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)

3. 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

4. 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

5. Contraindications to Heparinisation or Anti-Platelet Therapy:

• History of Heparin-Induced Thrombocytopenia (HIT)
• Increased bleeding risk (GI bleeding, traumatic head injury)

6. Pregnancy

7. Contrast allergy

8. 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)

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tan Tock Seng Hospital

OTHER

Sponsor Role: collaborator

National University Hospital, Singapore

OTHER

Sponsor Role: collaborator

Khoo Teck Puat Hospital

OTHER

Sponsor Role: collaborator

Changi General Hospital

OTHER

Sponsor Role: collaborator

Sengkang General Hospital

OTHER

Sponsor Role: collaborator

National Heart Centre Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Derek John Hausenloy

Role: PRINCIPAL_INVESTIGATOR

National Heart Centre Singapore

Locations

National University Hospital (NUH)

Singapore, , Singapore

Tan Tock Seng Hospital (TTSH)

Singapore, , Singapore

Khoo Teck Puat Hospital

Singapore, , Singapore

Changi General Hospital

Singapore, , Singapore

SengKang General Hospital

Singapore, , Singapore

Countries

Singapore

References

Bulluck H, Chong JH, Bryant J, Annathurai A, Chai P, Chan M, Chawla A, Chin CY, Chung YC, Gao F, Ho HH, Ho AFW, Hoe J, Imran SS, Lee CH, Lim B, Lim ST, Lim SH, Liew BW, Zhan Yun PL, Ong MEH, Paradies V, Pung XM, Tay JCK, Teo L, Ting BP, Wong A, Wong E, Watson T, Chan MY, Keong YK, Tan JWC, Hausenloy DJ; PITRI Investigators. Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial). Circulation. 2024 Jul 9;150(2):91-101. doi: 10.1161/CIRCULATIONAHA.124.068938. Epub 2024 May 14.

Reference Type: DERIVED

PMID: 38742915 (View on PubMed)

Bulluck H, Chan MHH, Bryant JA, Chai P, Chawla A, Chua TS, Chung YC, Fei G, Ho HH, Ho AFW, Hoe AJ, Imran SS, Lee CH, Lim SH, Liew BW, Yun PLZ, Hock MOE, Paradies V, Roe MT, Teo L, Wong AS, Wong E, Wong PE, Watson T, Chan MY, Tan JW, Hausenloy DJ. Platelet inhibition to target reperfusion injury trial: Rationale and study design. Clin Cardiol. 2019 Jan;42(1):5-12. doi: 10.1002/clc.23110. Epub 2018 Dec 17.

Reference Type: DERIVED

PMID: 30421441 (View on PubMed)

Other Identifiers

PITRI-01

Identifier Type: -

Identifier Source: org_study_id