Recurrent Stroke Prevention Clinical Outcome Study

NCT01198496 | Unknown Phase 4 DMC

• 2 other identifiers: RESPECT 1UMIN000002851
• Study Type: interventional
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Objectives and Hypothesis
2. 2.Objectives:
3. 3.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.
4. 4.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.

Conditions

Hypertension; Stroke; Blood Pressure

Keywords

hypertension; stroke; blood pressure

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• The incidence of events other than stroke

  Until the first recurrent stroke reaches a total of 339 between the two groups

Study Arms (1)

Blood pressure

EXPERIMENTAL

The incidence of recurrent stroke will be lower in a strict BP control group having lower BP target: less than 120/80 mmHg\* than in a standard BP control group having BP target less than 140/90 mmHg or less than 130/80 mmHg for current DM/CKD/old MI in patients with hypertension. * This study uses BP target: less than 120/80 mmHg that is sat up for this study rather than the BP target recommended in the Guidelines for the management of hypertension, Japanese Society of Hypertension 2009. * BP management is strongly recommended in patients with hypertension, DM, and/or CKD for prevention of recurrent stroke in the Japanese guidelines for the management of stroke 2009.

Drug: Losartan, Losartan and HCTZ, Amlodipine , Spironolactone

Interventions

Losartan, Losartan and HCTZ, Amlodipine , Spironolactone DRUG

\<Study drugs and treatment steps\> Step 1: Losartan 50 mg in principle (other ARB is usable) Step 2: Combination drug containing losartan 50 mg and hydrochlorothiazide 12.5 mg Step 3: Combination drug containing losartan 50mg and HCTZ 12.5mg + amlodipine 5 mg Step 4: Losartan 50 mg + combination drug containing losartan 50 mg and HCTZ 12.5 mg + amlodipine 5 mg Step 5: Losartan 50 mg + combination drug containing losartan 50 mg and HCTZ 12.5 mg + amlodipine 10 mg Step 6: Losartan 50 mg + combination drug containing losartan 50 mg and HCTZ 12.5 mg + amlodipine 10 mg + spironolactone 25 mg

Also known as: candesartan cilexetil, valsartan, telmisartan, olmesartan medoxomil

Blood pressure

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Biomedis International Ltd.: lead

Study Sites (1)

Jichi Medical Univercity

Shimotsuke, Tochigi, 329-0498, Japan

RECRUITING

Related Publications (3)

• Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.

  PMID: 36398903 DERIVED

• Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.

  PMID: 32905623 DERIVED

• Kitagawa K, Yamamoto Y, Arima H, Maeda T, Sunami N, Kanzawa T, Eguchi K, Kamiyama K, Minematsu K, Ueda S, Rakugi H, Ohya Y, Kohro T, Yonemoto K, Okada Y, Higaki J, Tanahashi N, Kimura G, Umemura S, Matsumoto M, Shimamoto K, Ito S, Saruta T, Shimada K; Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study Group. Effect of Standard vs Intensive Blood Pressure Control on the Risk of Recurrent Stroke: A Randomized Clinical Trial and Meta-analysis. JAMA Neurol. 2019 Nov 1;76(11):1309-1318. doi: 10.1001/jamaneurol.2019.2167.

  PMID: 31355878 DERIVED

Related Links

• RESPECT Study

MeSH Terms

Conditions

Hypertension; Stroke

Interventions

Losartan; Hydrochlorothiazide; Amlodipine; Spironolactone; candesartan cilexetil; Valsartan; Telmisartan; Olmesartan Medoxomil

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dihydropyridines; Pyridines; Lactones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Valine; Amino Acids, Branched-Chain; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Essential; Benzimidazoles

Study Officials

• Kazuyuki Shimada, MD

  RESPECT Study Group

  STUDY CHAIR

Central Study Contacts

Hiroko Usami, PhD

CONTACT

81-1-3-6252-3282; hiroko-u@biomedis.co.jp

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 28, 2010
• First Posted: September 10, 2010
• Study Start: October 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2019
• Last Updated: July 31, 2012

Record last verified: 2010-09

Locations

JP (1)