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

Primary Purpose

Myocardial Infarction, Diabetes Mellitus, Coronary Artery Disease

Status
Completed
Phase
Phase 4
Locations
Greece
Study Type
Interventional
Intervention
Ticagrelor 60 mg
Prasugrel 5mg
Sponsored by
Attikon Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myocardial Infarction focused on measuring ticagrelor, prasugrel

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Attikon University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Ticagrelor

Prasugrel

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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
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

Full Information

First Posted
December 23, 2017
Last Updated
March 2, 2019
Sponsor
Attikon Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03387826
Brief Title
Low Dose Ticagrelor Versus Low Dose Prasugrel in Patients With Prior Myocardial Infarction
Acronym
ALTIC-2
Official Title
A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor (60mg Bid) to Low Dose Prasugrel (5mg od) in Patients With Prior Myocardial Infarction
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
January 11, 2018 (Actual)
Primary Completion Date
January 31, 2019 (Actual)
Study Completion Date
January 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Attikon Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction, Diabetes Mellitus, Coronary Artery Disease, Renal Disease
Keywords
ticagrelor, prasugrel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Crossover Assignment
Masking
Outcomes Assessor
Masking Description
Single (outcome assessor)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ticagrelor
Arm Type
Experimental
Arm Description
Ticagrelor 60mg twice daily followed by Prasugrel 5mg once daily
Arm Title
Prasugrel
Arm Type
Active Comparator
Arm Description
Prasugrel 5m once daily followed by Ticagrelor 60mg twice daily
Intervention Type
Drug
Intervention Name(s)
Ticagrelor 60 mg
Intervention Description
Ticagrelor 60 mg twice daily
Intervention Type
Drug
Intervention Name(s)
Prasugrel 5mg
Intervention Description
Prasugrel 5 mg once daily
Primary Outcome Measure Information:
Title
Platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods
Description
Platelet reactivity measured in P2Y12 reaction units (PRU) at the end of the 2 study periods (pre-crossover and post-crossover).
Time Frame
14 days
Secondary Outcome Measure Information:
Title
High platelet reactivity rate at the end of the 2 study periods
Description
High platelet reactivity rate (defined as >208 PRU) at the end of the 2 study periods
Time Frame
14 days
Title
VerifyNow P2Y12 assay % inhibition, using the TRAP-induced response at the end of the 2 study periods
Description
VerifyNow P2Y12 assay % inhibition, using the TRAP-induced (BASE channel) response at the end of the 2 study periods
Time Frame
14 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of informed consent prior to any study specific procedures Post-menopausal female (defined as absence of any vaginal bleeding for a year) or male aged >50 years 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: Planned use of a P2Y12 receptor antagonist, dipyridamole, cilostazol, or anticoagulant therapy during the study period; Known allergy, intolerance, hypersensitivity to ticagrelor or prasugrel or any excipients, 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; Gastrointestinal bleeding within the previous 6 months or major surgery within the previous 30 days; 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). 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). 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dimitrios Alexopoulos, MD
Organizational Affiliation
Attikon Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Attikon University Hospital
City
Chaidari
ZIP/Postal Code
12462
Country
Greece

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35224730
Citation
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.
Results Reference
derived

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

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