To assess the safety, efficacy and net clinical benefit of clopidogrel versus the new antiplatelet drugs i.e. ticagrelor and prasugrel in patients older than 70 years.
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The first primary endpoint is the occurrence of any bleeding episode at 1 year
after randomisation and second primary endpoint is the net clinical benefit at
1 year after randomisation.
Secondary outcome
Secondary safety endpoints are bleeding events either CABG related or non-CABG
related, according to TIMI (10), PLATO (2), GUSTO (11), and BARC (12)
classification and composite of bleeding events within each classification at
30 days and 1 year after randomisation.
Secondary net clinical benefit endpoints are composites of death from any cause
other than vascular or bleeding causes, death from vascular causes, death from
bleeding causes (= fatal bleeding), MI (13), stroke, UA, TIA, other arterial
thrombosis, PLATO major and minor bleeding at 30 days and 1 year after
randomisation.
Secondary efficacy endpoints are death from any cause, death from
cardiovascular causes, death from cerebrovascular causes MI (13), stent
thrombosis as defined by ARC (14), UR, rehospitalization for ACS, stroke, TIA
or composites of these endpoints at 30 days and 1 year after randomisation.
Secondary endpoints in terms of quality of life are measurements obtained with
EuroQol 5D and SF36 questionnaires and frailty by using the Groningen Frailty
Indicator at one month and one year.
A secondary endpoint is the number of patients in whom the antiplatelet drug is
prematurely discontinued or switched to another drug leading to a cross-over.
Tertiary endpoints would be the evaluation of genetic variants on the response
to clopidogrel and prasugrel or ticagrelor in terms of efficacy and safety in a
candidate gene approach, Genome Wide Association Study or (next generation)
sequencing.
Tertiary endpoint would be the evaluation of frailty according to the Groningen
Frailty indicator (GFI * 4 would indicate a frail patient).
Background summary
Dual antiplatelet therapy is crucial in patients with an acute coronary
syndrome (ACS) to prevent artherothrombotic events. The recent guideline of the
European Society of Cardiology (ESC) based on PLATO en TRITON studies,
recommends ticagrelor or prasugrel, which also give more bleeding
complications. However, the representation of the elderly in clinical trials
is low and in a subgroup analysis of patients 75 years of age statistical
significance was not reached. The ESC guideline advises the use of the CRUSADE
risk score for risk stratification. However, based on the currently available
data it is not clear which antiplatelet treatment should be initiated in those
patients with a high bleeding risk, who also appear to have the highest
atherothrombotic risk.
Study objective
To assess the safety, efficacy and net clinical benefit of clopidogrel versus
the new antiplatelet drugs i.e. ticagrelor and prasugrel in patients older than
70 years.
Study design
Randomized, controlled, open label, multicenter study
Intervention
Patients randomized to clopidogrel will receive 75 mg daily for one year. Those
randomized to the new antiplatelet drugs will be treated with either ticagrelor
90 mg twice daily or prasugrel 10 mg daily (prasugrel 5 mg in patients *75
years or weight * 60 kg), according to hospital*s local standards. The
follow-up duration will be 1 year
Study burden and risks
The burden for patients participating in the study is that patients will be
contacted twice during the study; 3 months and 12 months after initial
diagnosis to fill out a questionnaire, to get information regarding the use of
antiplatelet drugs, changes in prescribed drugs and medical condition. At one
month and 12 months patients will also be requested to fill out EuroQol 5D and
SF36 questionnaires to asses quality of life and the Groningen Frailty
Indicator to assess frailty. The patient may be contacted by telephone if this
is necessary to complete follow-up data.
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Koekoekslaan 1
Nieuwegein 3430 EM
NL
Listed location countries
Age
Inclusion criteria
1) At least 70 years of age.
2) Hospitalization for NSTEMI or unstable angina according to the criteria of the ESC guideline.
Exclusion criteria
1) Contraindication to P2Y12 inhibitors i.e. clopidogrel, prasugrel or ticagrelor:
- Hypersensitivity to the active substance or to any of the excipients.
- History of intracranial bleeding or active pathological bleeding such as peptic ulcer or intracranial haemorrhage.
- Moderate to severe (Child-Pugh C) hepatic dysfunction.
- Use of strong CYP3A4 inhibitors (i.e. itraconazole, voriconazole, ketoconazole, erytromycin, clarithromycin, rifampicin, nefozodone, lopinavir, carbamazepine, fenytoïne, fenobarbital, ritonavir en atazanavir).
2) Unable or unwilling to give informed consent or have a life expectancy of less than one year.
3) Having received thrombolytic therapy within the previous 24 hours.
4) Severe renal function impairment needing dialysis.
5) Confirmed or persistent severe hypertension (Systolic Blood Pressure (SBP) > 180 mmHg and/or Diastolic Blood Pressure (DBP) >110 mmHg) at randomization.
6) At increased bleeding risk, at the investigator*s opinion, i.e. because of malignancy.
7) Cardiogenic shock (SBP * 80mmHg for >30 mins) or Intra-Aortic Balloon Pump (IABP) at the time of screening.
8) History of major surgery, severe trauma, fracture or organ biopsy within 90 days prior to randomisation.
9) Clinically significant out of range values for platelet count or haemoglobin at screening, in the investigator*s opinion.
10) ACS under dual antiplatelet therapy, e.g. aspirin with a P2Y12 inhibitor; clopidogrel, prasugrel, ticagrelor.
11) Patients with a known CYP2C19 genotype at the time of randomization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001403-37-NL |
| CCMO | NL44128.100.13 |
| Other | TC = 3991 |