Low Dose Ticagrelor Versus Low Dose Prasugrel in Patients With Prior Myocardial Infarction

NCT ID: NCT03387826

Last Updated: 2019-03-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-11
• Study Completion Date: 2019-01-31

Brief Summary

Taken together the results from DAPT and PEGASUS-TIMI54, it appears that physicians may consider extending beyond 1 year or reinitiating treatment with a thienopyridine or ticagrelor 60mg bid in patients with a prior MI and features of high ischemic and low bleeding risk. Comparative clinical or pharmacodynamic studies, however, between prasugrel 5 mg od and ticagrelor 60 mg bid in the chronic phase of stable post MI patients have not been performed.

In light of this, we believe that a dedicated pharmacodynamic study of ticagrelor 60 bid mg vs prasugrel 5 mg od in a PEGASUS-like population would be informative for the practicing clinician, thus setting the rationale for conducting this specifically designed investigation.

Detailed Description

This is a prospective, randomized, single blind, single center, crossover study. Eligible patients undergoing P2Y12 receptor antagonist therapy before screening will undergo a 14-day minimum washout period before randomization. Following screening/washout period (visit 1), patients will be randomized (visit 2, time 0) in 1:1 fashion to either prasugrel 5 mg od or ticagrelor 60 mg bid. Following 14±2 days (visit 3) patients will receive alternate treatment for additional 14 days (visit 4). Platelet reactivity assessment will be performed with the VerifyNow P2Y12 reaction assay at time 0, prior to first study drug dose. At visit 3 platelet function will be assessed at 2-4 hours post dose and prior to crossover. At visit 4 also platelet function will be assessed at 2-4 hours post study drug post dose. All patients will receive concomitant aspirin (100 mg/d) and standard secondary prevention medication.

The primary endpoint is the platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).

Conditions

Myocardial Infarction; Diabetes Mellitus; Coronary Artery Disease; Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor

Ticagrelor 60mg twice daily followed by Prasugrel 5mg once daily

Group Type: EXPERIMENTAL

Ticagrelor 60 mg

Intervention Type: DRUG

Ticagrelor 60 mg twice daily

Prasugrel 5mg

Intervention Type: DRUG

Prasugrel 5 mg once daily

Prasugrel

Prasugrel 5m once daily followed by Ticagrelor 60mg twice daily

Group Type: ACTIVE_COMPARATOR

Ticagrelor 60 mg

Intervention Type: DRUG

Ticagrelor 60 mg twice daily

Prasugrel 5mg

Intervention Type: DRUG

Prasugrel 5 mg once daily

Interventions

Ticagrelor 60 mg

Ticagrelor 60 mg twice daily

Intervention Type: DRUG

Prasugrel 5mg

Prasugrel 5 mg once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures

2. Post-menopausal female (defined as absence of any vaginal bleeding for a year) or male aged >50 years

3. A spontaneous MI (ST or Non ST segment elevation) 1 to 3 years before enrolment. In addition, at least one of the following high-risk features: age of 65 years or older, diabetes mellitus requiring medication, a second prior spontaneous MI, multivessel coronary artery disease, or non-end stage renal disease (estimated creatinine clearance of <60 ml per minute).

Exclusion Criteria

1. Planned use of a P2Y12 receptor antagonist, dipyridamole, cilostazol, or anticoagulant therapy during the study period;

2. Known allergy, intolerance, hypersensitivity to ticagrelor or prasugrel or any excipients,

3. Active pathological bleeding, severe hepatic impairment, a bleeding disorder or a history of an ischemic stroke or intracranial bleeding, a central nervous system tumor, or an intracranial vascular abnormality;

4. Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days;

5. Concomitant use of potent Cytochrome P450 3A4 (CYP3A4) inhibitors (atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin and voriconazole, grapefruit juice over 1 litre daily), CYP3A substrates with narrow therapeutic indices (cyclosporine, quinidine), or inducers (carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin, and rifapentine).

6. Increased risk of bradycardic events (e.g. known sick sinus syndrome or third degree AV block or previous documented syncope suspected to be due to bradycardia unless treated with a pacemaker).

7. Inability to adhere to the follow-up requirements or any other reason or condition that the investigator feels would place the patient at increased risk if the investigational therapy is initiated.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Attikon Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dimitrios Alexopoulos

Professor of Cardiology, National and Capodestrian University of Athens

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dimitrios Alexopoulos, MD

Role: PRINCIPAL_INVESTIGATOR

Attikon Hospital

Locations

Attikon University Hospital

Chaïdári, , Greece

Countries

Greece

References

Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Reference Type: DERIVED

PMID: 35224730 (View on PubMed)

Other Identifiers

AttikonH14005

Identifier Type: -

Identifier Source: org_study_id