Hypertension Clinical Trial
— RESPECTSOfficial title:
Phase IV Study for Effect of Intensive Blood-Pressure Control Using Anti-hypertensive Agents in Essential Hypertension With History of Stroke
1. Objectives and Hypothesis
1. Objectives:
This study evaluates whether strict BP management is useful for the prevention of
recurrent stroke.
Hypertensive patients with history of stroke are treated with stepwise multi-drug
therapy to achieve stricter BP target <120/80 mmHg in the strict BP control group
and less stricter BP target <140/90 mmHg or <130/80 mmHg for patients with current
DM/CKD/MI in the standard BP control group. The participants under the BP
treatment achieving their respective BP target will be followed for recurrence of
stroke. The study continues until the number of patients with the first recurrent
stroke reaches a total of 330 between the two groups. The occurrence rates of
recurrent stroke will be compared between the two groups.
2. Hypotheses The incidence of recurrent stroke will be lower in a strict BP control
group having lower BP target: <120/80 mmHg* than in a standard BP control group
having BP target <140/90 mmHg or <130/80 mmHg for current DM/CKD/MI in patients
with hypertension.
2. Study design This will be a multicenter, randomized, open-label study. The study
consists of a screening period, a titration period and a follow-up period. The
screening period is a period between the date of consent and the enrollment date.
Hypertensive patients with history of stroke are randomly assigned to either the strict
BP control group having the target of <120/80 mmHg or the standard BP control group
having the target of <140/90 mmHg without current DM, CKD or MI and <130/80 mmHg with
current DM, CKD or MI. The titration period is the period finding a treatment which
achieves target BP, and 24 weeks at maximum. Patients will be treated with stepwise
multi-drug therapy using an angiotensin-receptor antagonist, diuretic, calcium channel
blocker and aldosterone antagonist. The participants will be observed under the BP
management for their respective BP target. The study will be continued until the number
of patients with the first recurrent stroke reaches a total of 330 between two groups.
The follow-up period will be 3 years.
The recurrent rates of stroke in both groups will be compared from various aspects, and
strict BP management will be investigated on the usefulness in prevention of recurrent
stroke.
Rationale for Study Duration Predicting that strict BP control reduces the relative risk of
recurrent stroke by 30% during the planned observation period of 3 years, the number of
participants necessary to detect the recurrent stroke with rate of 2.5%/year and 7.5%/3
years is 2482 patients per group with a detection power of 90% and α-error of 0.05. A
drop-out rate is estimated as 20%.
Therefore, the study will be continued for 3 years until a total of 330 patients with
recurrent stroke in both groups are identified.
Rationale for Dosing Regimen One of ARB, losartan, is chosen for Step 1 therapy, because
angiotensin II receptor blocker (ARB) is preferred as the first line of anti-hypertensives.
Furthermore, a stepwise combination therapy of BP lowering drugs diuretic,
hydrochlorothiazide, and calcium channel blocker, amlodipine, will be used, because the
Japanese guidelines recommend the combination for BP control in prevention of recurrent
stroke. (Step 2 to Step 5). Finally (as Step 6), a selective aldosterone antagonist,
spironolactone, will be added for the treatment of with refractory hypertensive patients
whose BP does not reach to the target.
Treatment Plan The dosages of study drugs will be determined according to the package insert
for the drug.
Patients who are not treated with antihypertensive agent or treated with one
antihypertensive agent at enrollment will start from Step 1. Patients who are treated with
two antihypertensive agents at enrollment will start from Step 2.
In principle, treatment duration will be for 4 weeks at each step.
| Status | Recruiting |
| Enrollment | 5000 |
| Est. completion date | December 2019 |
| Est. primary completion date | December 2017 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 50 Years to 85 Years |
| Eligibility |
Inclusion Criteria: Participants include those with essential hypertension and history of stroke who satisfy the following criteria: - Outpatient - Onset of stroke(cerebral infarction/cerebral hemorrhage) occurred between 30 days and 3 years prior to the date of consent. - Drug adherence is ?80% during the screening period. - Mean of 2 baseline BP measurements(measured at outpatient clinic) within 30 days prior to the date of consent is either 180 >SBP ?130 mmHg or 110 >DBP ?80 mmHg (untreated -3 anti hypertensive agents patients). - Cerebral infarction with severity 3 or less in the modified Rankin scale. Exclusion Criteria: Patient who meets any one of the following criteria is excluded from the study. - Women who are pregnant, are possible pregnant, or are breastfeeding - Possible secondary hypertension - Severe hypertension (grade III or greater) with baseline SBP ?180 mmHg or DBP ?110 mmHg) - Myocardial infarction or undergoing angioplasty occurred within 3 months prior to the screening. - Current or previous heart failure with NYHA classification class III or more, or EF less than 35% - Severe bilateral carotid stenosis or major cerebral artery occlusion - Severe paralysis due to stroke (modified Rankin scale ? 4 ) - Current renal dysfunction (serum Cr ? 2.0 mg/dL right before the date of consent) - Current hepatic dysfunction with AST or ALT value ? 100 IU/mL right before the date of consent - Refractory hypertension treated with four or more antihypertensive drugs - Hypersensitivity or allergy to losartan and other angiotensin II receptor blockers, hydrochlorothiazide, amlodipine or sulfonamide derivative - Major surgery planned during the study period - Participants of other clinical studies within the last 30 days - Current malignancy (previous malignancy within 5 years after the end of treatment) excluding squamous-cell skin cancer - Previous and current subarachnoid hemorrhage - Definitive dementia 12) (based on a clinical diagnosis) - Patients who have difficulty in signing consent or who do not agree to the provided consent - Patients who are judged to be unsuitable for participating the study by the primary investigator or sub-investigator. |
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
| Country | Name | City | State |
|---|---|---|---|
| Japan | Jichi Medical Univercity | Shimotsuke | Tochigi |
| Lead Sponsor | Collaborator |
|---|---|
| Biomedis International Ltd. |
Japan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | the prevention of recurrent stroke. | Hypertensive patients with history of stroke are treated with stepwise multi-drug therapy to achieve BP target less than 120/80 mmHg in the strict BP group and BP target less than 140/90 mmHg or less than 130/80 mmHg for patients with DM/CKD/old MI in the standard BP group. The participants under the BP treatment achieving their respective BP target will be followed for recurrence of stroke. The study continues until the number of patients with the first recurrent stroke reaches a total of 339 between the two groups. | Until the first recurrent stroke reaches a total of 339 between the two groups | Yes |
| Secondary | The incidence of events other than stroke | Under the strict BP control, not only the recurrence of stroke but also occurrence of cardiovascular events (such as myocardial infarction and heart failure), angioplasty, and death will be reduced. Separate hypothesis: Additionally, occurrence and exacerbation of dementia is also decreased under the strict BP control in comparison with the standard control. |
Until the first recurrent stroke reaches a total of 339 between the two groups | Yes |
