TIcagrelor in Rotational Atherectomy to Reduce TROPonin Enhancement

NCT ID: NCT02505399

Last Updated: 2018-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2018-05-30

Brief Summary

Rotational atherectomy (RA) prior to angioplasty is the reference treatment for highly calcified atherosclerotic coronary lesions. It aims at fragmenting calcium deposits into microscopic particulates to allow less hazardous coronary revascularization and stenting. The main drawback associated with the procedure is the subsequent enhancement of platelet aggregation which promotes the distal embolization of micro-thrombi and atherosclerotic fragments. In order to limit these complications, a double antiplatelet therapy is required (generally Clopidogrel + Aspirin) when RA procedures are performed. Clopidogrel inhibits the protein P2Y12 which is a cornerstone in platelet aggregation. Ticagrelor is a new antiplatelet agent that provides faster and greater P2Y12 inhibition than Clopidogrel. It is currently indicated to reduce risk of cardiovascular events in patients hospitalized for coronary revascularization after an acute coronary syndrome. Ticagrelor has never been evaluated so far in stable coronary patients treated with rotational atherectomy prior to angioplasty.

Detailed Description

Rotational atherectomy (RA) prior to angioplasty is the reference treatment for highly calcified atherosclerotic coronary lesions. It aims at fragmenting calcium deposits into microscopic particulates to allow less hazardous coronary revascularization and stenting. The main drawback associated with the procedure is the subsequent enhancement of platelet aggregation which promotes the distal embolization of micro-thrombi and atherosclerotic fragments. In order to limit these complications, a double antiplatelet therapy is required (generally Clopidogrel + Aspirin) when RA procedures are performed. Clopidogrel inhibits the protein P2Y12 which is a cornerstone in platelet aggregation. It is characterized by a slow and variable transformation of a prodrug into an active metabolite and by a remaining risk of thrombosis and myocardial infarction. Ticagrelor is a new antiplatelet agent that provides faster and greater P2Y12 inhibition than Clopidogrel. It is currently indicated to reduce risk of cardiovascular events in patients hospitalized for coronary revascularization after an acute coronary syndrome. Ticagrelor has never been evaluated so far in stable coronary patients treated with rotational atherectomy prior to angioplasty.

Conditions

Atherosclerosis

Keywords

Rotational Atherectomy; clopidogrel; thrombosis; ticagrelor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

ticagrelor

In the intervention group, Ticagrelor will be administered orally, according to the following scheme:

• 180 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 90 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 90 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 90 mg twice daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

Group Type: EXPERIMENTAL

ticagrelor

Intervention Type: DRUG

Ticagrelor will be administered orally, according to the following scheme:

• 180 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 90 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 90 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 90 mg twice daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

clopidogrel

In the control group, Clopidogrel will be administered orally, according to the following scheme:

• 300 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 75 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 0 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 75 mg once daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

Group Type: ACTIVE_COMPARATOR

clopidogrel

Intervention Type: DRUG

Clopidogrel will be administered orally, according to the following scheme:

• 300 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 75 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 0 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 75 mg once daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

Interventions

ticagrelor

Ticagrelor will be administered orally, according to the following scheme:

• 180 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 90 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 90 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 90 mg twice daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

Intervention Type: DRUG

clopidogrel

Clopidogrel will be administered orally, according to the following scheme:

• 300 mg the evening preceding (and at least 6 hours before) rotational atherectomy (Day -1),
• 75 mg the following morning (D Day before rotational atherectomy and angioplasty),
• 0 mg the following evening (D Day after rotational atherectomy and angioplasty),
• 75 mg once daily the day after the procedure of rotational atherectomy and angioplasty (Day +1).

Intervention Type: DRUG

Other Intervention Names

ticagrelor per os; clopidrogel per os

Eligibility Criteria

Inclusion Criteria

• Stable coronary patient, or patient presenting with a non ST-elevation acute coronary syndrome without troponin elevation, or with troponin back to normal,
• Patient treated with a combination of Aspirin + Clopidogrel before hospitalization at the study center,
• Patient with at least one highly calcified coronary lesion eligible for rotational atherectomy prior to angioplasty,
• Patient agreed to participate after full information on the study.

Exclusion Criteria

• Acute coronary syndrome with ST-elevation,
• Plasma troponin level higher than 3 times the upper limit of the laboratory,
• Lesion located on a coronary bypass,
• Coronary thrombus diagnosed by angiography,
• Coronary dissection diagnosed by angiography,
• Left ventricular ejection fraction lower than 30%,
• Contra-indication to use Ticagrelor or Clopidogrel as listed in the Summary of Product Characteristics (SmPC, annex 1 & 2):

• Known hypersensitivity to the active substance or to the excipients,
• Active pathological bleeding,
• History of intracranial hemorrhage,
• Moderate to severe hepatic impairment,
• Co-administration with a strong cytochrome P450 3A4 inhibitor (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir),
• Other conditions at increased risk of bleeding:

• Congenital or acquired coagulation disorder
• Gastroduodenal bleeding within past 6 months,
• Recent major trauma or surgery within past 30 days,
• Concomitant use of fibrinolytics, oral anticoagulation, non-steroidal antiinflammatory drugs,
• Significant anemia,
• Increased risk of bradycardia,
• History of asthma or Chronic Obstructive Pulmonary Disease,
• Uric acid nephropathy,
• Ischemic stroke within 7 days,
• Heredity galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption,
• Concomitant use of a strong CYP3A4 inducer
• Concomitant use of CYP3A4 substrates with narrow therapeutic indices (e.g. cisapride, ergot alkaloids), simvastatin at a dose greater than 40 mg/d,
• Concomitant use of Selective Serotonin Reuptake inhibitors,
• Concomitant use of digoxin without close clinical and laboratory monitoring,
• Contra-indication to use Aspirin,
• Breast-feeding,
• Pregnancy,
• Adult protected by the law,
• Patient participating in another biomedical research.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Toulouse

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Didier Didier, PHD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

Clinique Pasteur

Toulouse, Haute-Garonne, France

Fédération de Cardiologie CHU TOULOUSE

Toulouse, Haute-Garonne, France

Hospices civils de Lyon

Lyon, , France

University Hospital

Nîmes, , France

Countries

France

Other Identifiers

RC31/14/7445

Identifier Type: -

Identifier Source: org_study_id