Low Dose Ticagrelor Versus Low Dose Prasugrel in Patients With Prior Myocardial Infarction (ALTIC-2)

A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor (60mg Bid) to Low Dose Prasugrel (5mg od) in Patients With Prior Myocardial Infarction

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Coronary Artery Disease; Diabetes Mellitus; Renal Disease
• Intervention / Treatment: Drug: Ticagrelor 60 mg; Drug: Prasugrel 5mg

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).

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Chaidari, Greece, 12462
    • Attikon University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; Ticagrelor 60mg twice daily followed by Prasugrel 5mg once daily	Drug: Ticagrelor 60 mg; Ticagrelor 60 mg twice daily; Drug: Prasugrel 5mg; Prasugrel 5 mg once daily
Active Comparator: Prasugrel; Prasugrel 5m once daily followed by Ticagrelor 60mg twice daily	Drug: Ticagrelor 60 mg; Ticagrelor 60 mg twice daily; Drug: Prasugrel 5mg; Prasugrel 5 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods	Platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High platelet reactivity rate at the end of the 2 study periods	High platelet reactivity rate (defined as >208 PRU) at the end of the 2 study periods	14 days
VerifyNow P2Y12 assay % inhibition, using the TRAP-induced response at the end of the 2 study periods	VerifyNow P2Y12 assay % inhibition, using the TRAP-induced (BASE channel) response at the end of the 2 study periods	14 days

Collaborators and Investigators

• Sponsor: Attikon Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2018
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: December 23, 2017
• First Submitted That Met QC Criteria: December 23, 2017
• First Posted (Actual): January 2, 2018

Study Record Updates

• Last Update Posted (Actual): March 5, 2019
• Last Update Submitted That Met QC Criteria: March 2, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: prasugrel; ticagrelor
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Infarction; Infarction; Coronary Artery Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Prasugrel Hydrochloride
• Other Study ID Numbers: AttikonH14005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No