P3AMI Antiplatelet Trial

NCT02376283 | Completed Phase 4 Results

• 1 other identifier: 2012-004-04-02-CARD
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

Major heart attacks are caused by a numerous factors, including sudden clot formation in a coronary artery leading to a blockage and heart muscle death. The clots are largely made of sticky clotting blood cells (platelets). A patient having a major heart attack is treated with emergency primary percutaneous coronary intervention (PPCI) where a wire and balloon are used to reopen the coronary artery and a stent (a slotted metal tube) is placed to keep the artery open. Aspirin, and one of two other antiplatelet drugs (prasugrel or ticagrelor) are given prior to PPCI to prevent further clots formation. Both antiplatelet drugs are taken in tablet form and in healthy stable patients these drugs take at least 30 min to 2 hours to exert an adequate effect. Often PPCI procedures are performed well within this timescale. It is possible that having a major heart attack limits the bodies ability to absorb the drugs also. In this study, patients with major or minor heart attacks will be given either prasugrel or ticagrelor as per licensed indications and guideline recommendations. A 15 ml blood sample will be taken at first balloon inflation to reopen the blocked artery, then after 20 minutes, 60 minutes, and 4 hours after taking the drugs. Each blood sample will be subjected to a variety of tests to determine antiplatelet drug activity. This study will identify which of the two agents used are working effectively during PPCI, given the very short timescales involved. It will also show if patients with major heart attacks absorb the drugs less well than patients with less severe heart attacks. In the future it might be that an intravenous agent will be more valuable in the setting of PPCI.

Conditions

Heart Attack

Keywords

STEMI; NSTEMI; PPCI

Outcome Measures

Primary Outcomes (2)

• Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by Verify Now Point of Care Assay and Expressed as P2Y12 Reaction Units (PRU)

  Balloon Inflation as Baseline, 20, 60, 240 minutes

• Pharmacokinetic Quantification of Plasma Concentration of Clopidogrel and Prasugrel Active Metabolite and Ticagrelor Parent Compound and Active Metabolite Assessed Using Liquid Chromatography in Tandem With Mass Spectrometry (LC-MS/MS) Expressed as ng/ml

  The parent compound of Ticagrelor was also analysed within the same patient group of Ticagrelor as it is a directly acting agent that does not require metabolic conversion to its active form.

  Balloon Inflation as Baseline, 20, 60, 240 minutes

Secondary Outcomes (1)

• Pharmacodynamic Assessment of Degree of Platelet Inhibition as Determined by VASP (Vasodilator Stimulated Phosphoprotein Phosphorylation) Flow Cytometry and Expressed as %PRI (Platelet Reactivity Index)

  Balloon Inflation as Baseline, 20, 60, 240 minutes

Study Arms (6)

STEMI prasugrel

OTHER

Patients with diabetes mellitus admitted with STEMI who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel Loading (60mg) and maintenance (10mg per day).

Drug: Prasugrel

STEMI clopidogrel

OTHER

Patients admitted with STEMI over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).

Drug: Clopidogrel

NSTEMI clopidogrel

OTHER

Patients admitted with NSTEMI/UA over the age of 75 or under 60 Kg receiving clopidogrel loading (600 mg) and then maintenance (75mg per day).

Drug: Clopidogrel

Patients with NSTEMI

OTHER

who are under 75 years of age and greater than 60Kg in weight receiving Prasugrel loading (60mg) however: - i. After sample collection patients treated with intracoronary stent placement on the same day as loading will receive prasugrel maintenance dose (10mg per day) as per licensing agreement for prasugrel ii. After sample collection patients who are not stented after loading will receive clopidogrel maintenance dose (75mg per day).

Drug: Prasugrel; Drug: Clopidogrel

Patients admitted with STEMI receiving ticagrelor loading

OTHER

Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)

Drug: ticagrelor

Patients Admitted with NSTEMI receiving ticagrelor loading

OTHER

Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day).

Drug: ticagrelor

Interventions

Prasugrel DRUG

Patients with NSTEMI; STEMI prasugrel

Clopidogrel DRUG

NSTEMI clopidogrel; Patients with NSTEMI; STEMI clopidogrel

ticagrelor DRUG

Patients Admitted with NSTEMI receiving ticagrelor loading; Patients admitted with STEMI receiving ticagrelor loading

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients presenting with STEMI for PCI (characterized by chest discomfort, and prominent STsegment elevation)
• Patients presenting with NSTEMI (characterized by chest discomfort, raised levels of myocardial enzymes and/or STsegment depression or prominent T wave inversion)
• Able to give verbal consent (STEMI patients pre procedure) and/or written consent (STEMI after procedure and NSTEMI patients prior to enrolment).
• Age\>18 years of age
• Able to take Aspirin and either prasugrel or ticagrelor.
• Have no concurrent septic or inflammatory illness
• Thienopyridine naive

You may not qualify if:

• Be unable to provide verbal and written consent
• Allergic to aspirin or any of the P2Y12 antagonists in the trial
• Have preexisting cardiogenic shock
• Have a concurrent septic or inflammatory disease e.g. rheumatoid arthritis, lupus, pneumonia.
• Already taking a P2Y12 inhibitor
• Known bleeding diathesis
• Patients under 75 years of age or under 60 kg or those who have had a previous stroke/transient ischaemic attack, will not be eligible for prasugrel but rather ticagrelor.
• Patients with a history of intracranial haemorrhage will not receive prasugrel or ticagrelor but rather will receive treatment with clopidogrel.

Sponsors & Collaborators

• The Royal Wolverhampton Hospitals NHS Trust: lead

Study Sites (1)

The Royal Wolverhampton NHS Trust

Wolverhampton, West Midlands, WV10 0QP, United Kingdom

Location

MeSH Terms

Conditions

Myocardial Infarction; ST Elevation Myocardial Infarction; Non-ST Elevated Myocardial Infarction

Interventions

Prasugrel Hydrochloride; Clopidogrel; Ticagrelor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Ticlopidine; Thienopyridines; Pyridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Adenosine; Purine Nucleosides; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Prof James Cotton
• Organization: The Royal Wolverhampton NHS Trust

jamescotton@nhs.net

01902307999

Study Officials

• James Cotton, MD, FRCP

  The Royal Wolverhampton NHS Trust

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2015
• First Posted: March 3, 2015
• Study Start: March 9, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: February 10, 2020
• Results First Posted: September 18, 2019

Record last verified: 2020-01

Locations

GB (1)