Transition From Ticagrelor to Clopidogrel Following Acute Coronary Syndrome: To Bolus or Not?

NCT02054663 | Completed Phase 4 DMC

• 1 other identifier: 20130605-01H
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

After a heart attack patients are routinely started on drugs to inhibit platelets. Ticagrelor is a powerful anti-platelet drug with clinical benefits. However it must be discontinued in some, because of increased risk of bleeding or intolerance. These patients need to be transitioned to another agent, such as Clopidogrel. At present, there is no clinical consensus on the optimal strategy for this switch. Some clinicians elect to give a bolus dose of clopidogrel with 600mg, while others start directly with a 75mg daily dose, with no evidence regarding the benefits or potential complications associated with each strategy. The present proposal will evaluate the pharmacodynamics of 2 strategies with specialized platelet function testing. We hypothesize that a bolus dose of clopidogrel during the switch will confer better ischemic protection without increasing bleeding risk for patients undergoing a switch in therapy.

Conditions

Acute Coronary Syndrome

Keywords

Acute coronary syndrome; Coronary artery disease; Antiplatelet therapy; Ticagrelor; Clopidogrel

Outcome Measures

Primary Outcomes (1)

• Platelet inhibition as assessed by P2Y12 reaction Unit (PRU) after transition from Ticagrelor to Clopidogrel.

  Post randomization, blood samples at scheduled time points will be collected. Samples would enable measurement of platelet inhibition using the VerifyNow P2Y12 assay. Blood samples will be collected at baseline (prior to clopidogrel dose), 12, 24, 48, 54, 60 and 72 hours post initiation of therapy. The primary endpoint is the difference in platelet inhibition between our 2 different groups (bolus vs no bolus), as measured by P2Y12 reaction unit (PRU) using the VerifyNow assay. The PRUs have now been widely used and accepted as a measure of platelet function in the research setting. PRU will be collected at the above mentioned time points. The primary outcome will be platelet function expressed as PRUs as a continuous variable over the 72 hour time period and compared between the 2 groups.

  72 hours

Secondary Outcomes (1)

• The difference in platelet inhibition (as expresses as PRU) between the two groups at specified time points.

  72 hours

Other Outcomes (1)

• Differences in clinical outcomes between the 2 groups within 30 days post transition.

  30 days post transition

Study Arms (2)

Bolus

EXPERIMENTAL

Patients randomized to this arm will receive a 600mg bolus dose of clopidogrel at the time of switching from ticagrelor to clopidogrel, followed by 75mg daily.

Drug: Clopidogrel

no bolus

EXPERIMENTAL

Individuals randomized to this arm will receive 75mg of clopidogrel at the time of the transition followed by a daily dose of 75mg orally.

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

Patients on ticagrelor following an acute coronary syndrome, being transitioned to clopidogrel will be randomized to either a one time 600mg bolous dose of clopidogrel followed by 75mg daily or just starting at 75mg daily without a bolous dose.

Also known as: Plavix

Bolus; no bolus

Eligibility Criteria

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

You may qualify if:

• age \> 18,
• admission for acute coronary syndrome,
• on dual anti-platelet therapy (including ticagrelor)
• Being transitioned to clopidogrel by their treating physician
• provided informed consent

You may not qualify if:

• Bleeding/intolerance to clopidogrel
• Thrombocytopenia (platelet count \< 100, 000 per uL)
• Hematocrit \<30% or \>52%
• treatment with glycoprotein IIb/IIIa inhibitor, 24 hours prior to randomization

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (1)

• Pourdjabbar A, Hibbert B, Chong AY, Le May MR, Labinaz M, Simard T, Ramirez FD, Lugomirski P, Maze R, Froeschl M, Glover C, Dick A, Marquis JF, Bernick J, Wells G, So DY; CAPITAL Investigators. A randomised study for optimising crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome. The CAPITAL OPTI-CROSS Study. Thromb Haemost. 2017 Jan 26;117(2):303-310. doi: 10.1160/TH16-04-0340. Epub 2016 Oct 20.

  PMID: 27761582 DERIVED

MeSH Terms

Conditions

Acute Coronary Syndrome; Coronary Artery Disease

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Derek So, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Staff Interventional cardiologist

Study Record Dates

• First Submitted: January 27, 2014
• First Posted: February 4, 2014
• Study Start: December 1, 2013
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: March 31, 2015

Record last verified: 2015-03

Locations

CA (1)