Platelet Inhibition to Target Reperfusion Injury

NCT03102723 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: PITRI-01
• Study Type: interventional
• Target: 228
• Locations: 1 country
• Sites: 5

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.

Conditions

STEMI

Keywords

STEMI; primary percutaneous coronary intervention (PPCI); cangrelor; reperfusion

Outcome Measures

Primary Outcomes (1)

• Myocardial infarct size by CMR at Day 2 to 7

  This will be measured by CMR (mass of late gadolinium enhancement expressed as a percentage of the LV mass).

  2-7 days

Secondary Outcomes (12)

• Microvascular obstruction to calculate myocardial interstitial volume

  2-7 days

• Myocardial salvage index

  2-7 days

• Angiographic markers of successful reperfusion

  2 to 3 hours

• Myocardial infarct size by CMR at 6 months

  6 months

• Post-MI LV remodeling by measuring LV ejection fraction and indexed LV end systolic and diastolic volumes and mass

  6 months

Study Arms (2)

Cangrelor

EXPERIMENTAL

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

Drug: Cangrelor

Placebo

PLACEBO COMPARATOR

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

Drug: Cangrelor

Interventions

Cangrelor 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.

Also known as: Kengreal

Cangrelor; Placebo

Eligibility Criteria

• Age: 21 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Heart Centre Singapore: lead
• Tan Tock Seng Hospital: collaborator
• National University Hospital, Singapore: collaborator
• Khoo Teck Puat Hospital: collaborator
• Changi General Hospital: collaborator
• Sengkang General Hospital: collaborator

Study Sites (5)

National University Hospital (NUH)

Singapore, 119228, Singapore

Location

Tan Tock Seng Hospital (TTSH)

Singapore, 308433, Singapore

Location

Khoo Teck Puat Hospital

Singapore, 768828, Singapore

Location

Changi General Hospital

Singapore, S529889, Singapore

Location

SengKang General Hospital

Singapore, S544886, Singapore

Location

Related Publications (2)

• 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.

  PMID: 38742915 DERIVED

• 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.

  PMID: 30421441 DERIVED

MeSH Terms

Conditions

ST Elevation Myocardial Infarction

Interventions

cangrelor

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Study Officials

• Derek John Hausenloy

  National Heart Centre Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2017
• First Posted: April 6, 2017
• Study Start: October 1, 2017
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: April 26, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (5)