Stroke
Conditions
Brief summary
The purpose of the trial is to determine if extended-release dipyridamole + aspirin \[Aggrenox, Asasa ntin\] is superior to clopidogrel \[Plavix\], and if telmisartan \[Micardis, Gliosartan, Kinzal, Kinzalm ono, Predxal, Pritor, Samertan, Telmisartan\] is superior to placebo, in the presence of background antihypertensive therapy, in prevention of a second stroke in patients who have recently suffered a stroke and therefore are at high risk of suffering another one.
Interventions
Sponsors
GlaxoSmithKline
Bayer
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female subjects 55 year or older who have suffered an ischemic stroke within the past 90 days and who meet all other inclusion criteria. Include also patients of ages 50 - 54 years and/or 90 to 120 days after the qualifying stroke provided the patient has at least two of the following additional risk factors: * Diabetes mellitus * Hypertension (systolic BP ¿ 140 or diastolic BP ¿ 90) * Smoker at time of qualifying stroke * Obesity (BMI\>30; BMI=weight (kg)/\[height (m)\]2) * Previous vascular disease (stroke, MI, or peripheral arterial disease prior to qualifying stroke) * End-organ-damage (retinopathy, LVH, or microalbuminuria) * Hyperlipidemia
Exclusion criteria
hemorrhagic stroke (must be ruled out by imaging);unable to give informed consent; known brain tumor, severe renal or hepatic insufficiency, current active peptic ulcer disease, severe coronary artery disease including unstable angina pectoris or an MI within the previous 3 months,or history of a hemostatic disorder or systemic bleeding ;hyperkalemia;uncorrected volume or sodium depletion; pre-stroke history of dementia;modified Rankin score greater than 4;qualifying stroke induced by surgical or cardiovascular procedure;uncontrolled hypertension at entry above 180/110 mmHg (goal BPs are lower); SBP 120 mmHg or less for hospitalized patients; currently taking an ARB and not able or willing to switch to alternative; required or planned continuing treatment with antithrombotics or anticoagulants including heparin or warfarin or non-study platelet inhibitors; syndrome of asthma, rhinitis and nasal polyps;scheduled for major surgery, carotid endarterectomy, or carotid angioplasty (4 weeks post surgery is allowed);unlikely to be released from hospital following the qualifying stroke or presence of a severe disability likely to lead to being bedridden or demented or a non-vascular disease or condition which makes it unlikely that the patient will survive to the end of the trial; history of thrombocytopenia or neutropenia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Antiplatelet Comparison Only) | time since randomization; follow-up period is 1.5 to 4.4 years |
| Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Telmisartan vs. Placebo Only) | time since randomization; follow-up period is 1.5 to 4.4 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Composite Outcome of Stroke, Myocardial Infarction (MI), or Vascular Death (Antiplatelet Comparison Only) | time since randomization; follow-up period is 1.5 to 4.4 years | Number of patients with any of stroke, myocardial infarction, vascular death |
| Composite Outcome of Stroke, Myocardial Infarction, Vascular Death, or New or Worsening Congestive Heart Failure (CHF) (Telmisartan vs. Placebo Only) | time since randomization; follow-up period is 1.5 to 4.4 years | Number of patients with any of stroke, myocardial infarction, vascular death, or new or worsening congestive heart failure |
| Number of Patients With New Onset of Diabetes (Telmisartan vs. Placebo Only) | Randomization to final patient contact | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, El Salvador, Finland, France, Germany, Greece, Hong Kong, India, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Norway, Portugal, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Sept 2003 - July 2006; 695 centres in 35 countries
Pre-assignment details
No screening period
Participants by arm
| Arm | Count |
|---|---|
| Aspirin + Extended Release Dipyridamole / Telmisartan 25 milligrams (mg) aspirin + 200 mg extended-release dipyridamole, twice daily, capsule / telmisartan 80 mg, once daily, tablet | 5,086 |
| Aspirin + Extended Release Dipyridamole / Placebo 25 mg aspirin + 200 mg extended-release dipyridamole, twice daily, capsule / placebo tablet | 5,095 |
| Clopidogrel / Telmisartan clopidogrel 75 mg, once daily, tablet / telmisartan 80 mg, once daily, tablet | 5,060 |
| Clopidogrel / Placebo clopidogrel 75 mg, once daily, tablet / placebo tablet | 5,091 |
| Total | 20,332 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 |
| Overall Study | Death | 360 | 352 | 369 | 365 |
| Overall Study | Lost to Follow-up | 12 | 20 | 15 | 16 |
| Overall Study | No disposition data available | 1 | 1 | 1 | 1 |
| Overall Study | Other | 0 | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 14 | 30 | 27 | 28 |
Baseline characteristics
| Characteristic | Aspirin + Extended Release Dipyridamole / Telmisartan | Aspirin + Extended Release Dipyridamole / Placebo | Clopidogrel / Telmisartan | Clopidogrel / Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.0 years STANDARD_DEVIATION 8.5 | 66.2 years STANDARD_DEVIATION 8.6 | 66.2 years STANDARD_DEVIATION 8.6 | 66.2 years STANDARD_DEVIATION 8.5 | 66.1 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 1802 Participants | 1851 Participants | 1817 Participants | 1840 Participants | 7310.0 Participants |
| Sex: Female, Male Male | 3284 Participants | 3244 Participants | 3243 Participants | 3251 Participants | 13022.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1,856 / — | 1,810 / — | 866 / — | 810 / — |
| serious Total, serious adverse events | 1,145 / — | 1,124 / — | 1,225 / — | 1,163 / — |
Outcome results
Primary
Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Antiplatelet Comparison Only)
Time frame: time since randomization; follow-up period is 1.5 to 4.4 years
Population: Patients were analyzed as randomized and were included in the analysis until final patient contact regardless of whether they were still on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin + Extended Release Dipyridamole | Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Antiplatelet Comparison Only) | 916 Participants |
| Clopidogrel | Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Antiplatelet Comparison Only) | 898 Participants |
Comparison: ASA+ER-DP vs clopidogrelp-value: 0.78395% CI: [0.92, 1.11]Cox Proportional Hazard model
Primary
Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Telmisartan vs. Placebo Only)
Time frame: time since randomization; follow-up period is 1.5 to 4.4 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin + Extended Release Dipyridamole | Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Telmisartan vs. Placebo Only) | 880 Participants |
| Clopidogrel | Number of Patients With First Recurrent Stroke of Any Type, Fatal or Nonfatal (Telmisartan vs. Placebo Only) | 934 Participants |
Comparison: Telmisartan vs placebop-value: 0.231295% CI: [0.86, 1.04]Cox Proportional Hazard model
Secondary
Composite Outcome of Stroke, Myocardial Infarction (MI), or Vascular Death (Antiplatelet Comparison Only)
Number of patients with any of stroke, myocardial infarction, vascular death
Time frame: time since randomization; follow-up period is 1.5 to 4.4 years
Population: Patients were analyzed as randomized and were included in the analysis until final patient contact regardless of whether they were still on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin + Extended Release Dipyridamole | Composite Outcome of Stroke, Myocardial Infarction (MI), or Vascular Death (Antiplatelet Comparison Only) | 1333 Participants |
| Clopidogrel | Composite Outcome of Stroke, Myocardial Infarction (MI), or Vascular Death (Antiplatelet Comparison Only) | 1333 Participants |
Comparison: ASA+ER-DP vs Clopidogrelp-value: 0.829295% CI: [0.92, 1.07]Cox Proportional Hazard model
Secondary
Composite Outcome of Stroke, Myocardial Infarction, Vascular Death, or New or Worsening Congestive Heart Failure (CHF) (Telmisartan vs. Placebo Only)
Number of patients with any of stroke, myocardial infarction, vascular death, or new or worsening congestive heart failure
Time frame: time since randomization; follow-up period is 1.5 to 4.4 years
Population: Patients were analyzed as randomized and were included in the analysis until final patient contact regardless of whether they were still on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin + Extended Release Dipyridamole | Composite Outcome of Stroke, Myocardial Infarction, Vascular Death, or New or Worsening Congestive Heart Failure (CHF) (Telmisartan vs. Placebo Only) | 1367 Participants |
| Clopidogrel | Composite Outcome of Stroke, Myocardial Infarction, Vascular Death, or New or Worsening Congestive Heart Failure (CHF) (Telmisartan vs. Placebo Only) | 1463 Participants |
Comparison: Telmisartan vs Placebop-value: 0.107395% CI: [0.87, 1.01]Cox Proportional Hazard model
Secondary
Number of Patients With New Onset of Diabetes (Telmisartan vs. Placebo Only)
Time frame: Randomization to final patient contact
Population: Patients who did not have diabetes mellitus at baseline were analyzed as randomized and were included in the analysis until final patient contact regardless of whether they were still on treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aspirin + Extended Release Dipyridamole | Number of Patients With New Onset of Diabetes (Telmisartan vs. Placebo Only) | 125 Participants |
| Clopidogrel | Number of Patients With New Onset of Diabetes (Telmisartan vs. Placebo Only) | 151 Participants |
Comparison: Telmisartan vs Placebop-value: 0.100795% CI: [0.65, 1.04]Cox Proportional Hazard model