The overall safety objective of this study is to assess the safety and tolerability of long-term therapy with ticagrelor compared to placebo in patients with T2DM at high risk of CV events, with or without background low-dose ASA therapy. Bleeding…
ID
Source
Brief title
Condition
- Cardiac disorders, signs and symptoms NEC
- Diabetic complications
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy variable is time from randomisation to first occurrence of
any event from the composite of CV death, MI or stroke (ischaemic, haemorrhagic
or unknown etiology).
Secondary outcome
The secondary objectives of the study (presented in hierarchical order) are to
compare the effect of long-term treatment with ticagrelor vs. placebo for:
1. Prevention of the composite of all-cause death, MI or stroke. The efficacy
variable is time from randomisation to first occurrence of any event from the
composite of all-cause death, MI or stroke
2. Prevention of CV death. The efficacy variable is time from randomisation to
death of CV cause
3. Prevention of all-cause death. The efficacy variable is time from
randomisation to death of any cause.
Background summary
Cardiovascular disease (CVD), which includes coronary heart disease (CHD),
cerebrovascular disease, and peripheral artery disease (PAD), is the leading
cause of death in most developed countries. In the United States, CVD accounted
for approximately 1 of every 3 deaths in 2009. The totality of evidence from
basic research, clinical investigations, observational epidemiologic studies,
and randomised clinical trials has provided strong support for the net benefits
of acetylsalicylic acid (ASA)/AspirinTM in decreasing the risk of CVD events in
a wide range of patients with established CHD. Diabetes substantially increases
the risk of major cardiovascular (CV) complications in patients with and
without established CVD (such that most patients with diabetes die of CV
diseases.
Study objective
The overall safety objective of this study is to assess the safety and
tolerability of long-term therapy with ticagrelor compared to placebo in
patients with T2DM at high risk of CV events, with or without background
low-dose ASA therapy. Bleeding events will be analyzed using the Thrombolysis
in Myocardial Infarction Study Group (TIMI) definitions, those used in the
PLATO (PLATelet inhibition and patient Outcomes) study, and the Bleeding
Academic Research Consortium (BARC) definitions. Specific focus will be on:
* Time to first TIMI Major bleeding event (primary safety objective)
* Time to first TIMI Major or Minor bleeding event
* Time to first PLATO Major bleeding event
*Time to permanent discontinuation of study medication due to any bleeding
event.
Non-serious AEs of interest (ie, dyspnoea, renal impairment, bradyarrhythmia,
gout, and pneumonia), adverse events that leads to permanent discontinuation of
study medication (DAEs) and all serious adverse events (SAEs) will be reviewed
within the context of the earlier safety experience with the drug.
Study design
This is an event-driven, randomised, double blind, placebo controlled, parallel
group, international multi-centre study to evaluate the effect of ticagrelor bd
vs. placebo for prevention of major CV events in patients with T2DM at high
risk of CV events, but without a medical history of previous MI or stroke.
Patients will be managed consistent with local standard of care including
provision of dietary and lifestyle advice according to local diabetes treatment
guidelines. Use of low-dose acetylsalicylic acid (ASA)/AspirinTM 75-150 mg once
daily (od), is allowed if clinically indicated, as judged by the investigator.
Intervention
Patient will receive either ticagrelor bd orally or corresponding placebo.
Study burden and risks
The patient is asked to visit the site a maximum of 15 times and will receive a
maximum of 12 telephone calls during the duration of the trial.
The patient will be asked to complete a questionaire 12 times max.
The patient will undergo a physical examination at the beginning of the trial
and will have an electro cardiogram (ECG) at the randomisation visit.
Woman of childbearing potential have to provide a urine sample for a pregnancy
test.
At the randomisation visit a blood sample will be taken after at least 6 hours
of fasting.
The study medication may cause some side effects.
Taking of a blood sample may cause some discomfort.
Prinses Beatrixlaan 582
Den Haag 2595 BM
NL
Prinses Beatrixlaan 582
Den Haag 2595 BM
NL
Listed location countries
Age
Inclusion criteria
1. Signed Informed Cosnent
2. Men or women *50 years of age
3. Diagnosed with T2DM defined by ongoing glucose lowering drug treatment prescribed by a physician for treatment of T2DM since at least 6 months prior to Visit 1
4. At high risk of CV events, defined as history of percutaneous coronary intervention or coronary artery bypass graft or angiographic evidence of * 50% lumen stenosis of at least 1 coronary artery
Exclusion criteria
1. Previous MI (with the exception of definite secondary MI [e.g., due to coronary revascularization procedure, profound hypotension, hypertensive emergency, tachycardia, or profound anaemia])
2. Previous stroke (transient ischaemic attacks [TIA] is not included in the stroke definition)
3. Planned use of ADP receptor antagonists (e.g., clopidogrel, ticlopidine, prasugrel), dipyridamole, or cilostazol. Planned use of ASA treatment at doses >150 mg od.;
4. Planned coronary, cerebrovascular, or peripheral arterial revascularization.;
5. Anticipated concomitant oral or intravenous therapy with strong cytochrome P450 3A4 (CYP3A4) inhibitors or CYP3A4 substrates with narrow therapeutic indices that cannot be stopped for the course of the study;
* Strong inhibitors: ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin (but not erythromycin or azithromycin), nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir.;
* CYP3A4 substrates with narrow therapeutic index: quinidine, simvastatin at doses >40 mg daily or lovastatin at doses >40 mg daily;
6. Need for chronic oral anticoagulant therapy or chronic low-molecular-weight heparin (at venous thrombosis treatment not prophylaxis doses);
7. Patients with known bleeding diathesis or coagulation disorder, or with uncontrolled hypertension (defined as a systolic BP *180 mmHg and/or diastolic BP *100 mmHg);
8. History of previous intracerebral bleed at any time, gastrointestinal (GI) bleed within the past 6 months, or major surgery within 30 days;
9. Increased risk of bradycardic events (e.g., known sick sinus syndrome, second or third degree AV block or previous documented syncope suspected to be due to bradycardia) unless treated with a pacemaker;
10. Known severe liver disease (e.g., ascites and/or clinical signs of coagulopathy);
11. Renal failure requiring dialysis;
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 | EUCTR2013-003519-23-NL |
| CCMO | NL46981.028.13 |