Optimization of Blood Pressure Management After Acute Ischemic Stroke and Its Prognostic Significance

Sponsor

Seoul National University Bundang Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT03024476

Collaborator

Daiichi Sankyo Korea Co., Ltd. (Industry)

Enrollment

Locations

Arms

15.2

Actual Duration (Months)

22.3

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

BOSS-Trial I is a phase 2 clinical trial with the following objectives;

to prove the feasibility of a Bluetooth-equipped sphygmomanometer system in real-world clinical practice and wireless connection to the main server;
to prove the feasibility of the BP management strategy, including the pre-specified BP range, BP management algorithm, and behavioral; and
to gather information for the phase 3 trial including BP variability indices and their potentials as a treatment guidance.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke Hypertension	Behavioral: Behavioral intensification Drug: Pharmacological intensification based on olmesartan Device: Bluetooth-equipped sphygmomanometer	Phase 2

Detailed Description

Elevated blood pressure is an established risk factor for recurrent stroke and vascular events in ischemic stroke survivors, but
Current guideline (JNC VIII) has omitted or only partially covered a number of practical and important issues as follow;
When and how we measure blood pressure?
Is it justifiable to apply the same blood pressure threshold for office BP and home BP?
Should stroke survivors be treated by the same BP goal for non-stroke subjects?
Is it justifiable to apply the universal BP threshold for different mechanisms of ischemic stroke?
Is it really about only blood pressure or might it really be "beyond blood pressure?"
Lifestyle modification should accompany all the pharmacological intervention but is usually in adequate to initiate behavioral changes.
Frequent BP measurement at home will provide more detailed and reliable information than occasional office BP's.

Study Design

Study Type:

Interventional

Actual Enrollment :

67 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Optimization of Blood Pressure Management After Acute Ischemic Stroke and Its Prognostic Significance: Prospective, Randomized, Open, Blinded Outcome Evaluation, and Feasibility Trial

Actual Study Start Date :

Sep 1, 2016

Actual Primary Completion Date :

Dec 7, 2017

Actual Study Completion Date :

Dec 7, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensive management arm Description: Interventions in the intensive management arm consist of 1) behavioral intensification and 2) pharmacological intensification based on olmesartan Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups). Regarding behavioral intensification, an automated texting and call for breakthrough visit will be sent from the main server to encourage regular measurements of BP and maintain a desirable goad of BP. Regarding pharmacological intensification, a specific algorithm for BP-lowering medication prescription will be provided to the responsible physicians by the steering committee.	Behavioral: Behavioral intensification Suggested algorithm for behavioral intensification: If frequency of BP measurement ≤5 in a week, send a texting message If frequency of BP measurement ≤3 in a week, make a telephone contact by research nurse Target range of home-systolic blood pressure: 110 - 135 If rate of outlier exceeds 50% in a week (based on ≥5 measurements in a week), make a telephone contact by research nurse (applied at least 2 weeks after randomization). A call for breakthrough visit may be issued when clinically required (decided by the institutional investigator) If frequency of BP measurement ≥ 10 in a week and frequency of outlier = 0 in a week, send a texting message to encourage and compliment on excellent BP management Drug: Pharmacological intensification based on olmesartan Study drug will be provided from the roll-in period. Step I: Use olmesartan 20 mg only if mean systolic blood pressure ≤150 mm Hg during the immediate past 2 days Use olmesartan 40 mg if mean systolic blood pressure >150 during the immediate past 2 days Step II: olmesartan 20 mg or 40 mg + amlodipine 5 mg Step III: olmesartan 20 mg or 40 mg + amlodipine 10 mg Step IV: olmesartan 20 mg or 40 mg + amlodipine 10 mg + hydrochlorothiazide 12.5 mg If blood pressure profile showed high degree variability to evoke clinical concern, consider discontinuation of hydrochlorothiazide or reduction of olmesartan dose. Use of beta-blockers is permitted if clinically indicated. At each clinic visit regardless of regular or breakthrough visit, follow the pharmacological intensification rule. Device: Bluetooth-equipped sphygmomanometer Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. (Identical for both intervention and control groups) Every blood pressure and heart rate measured will be encrypted and stored in the main server. (Identical for both intervention and control groups)
Active Comparator: Control arm Description: Other than a bluetooth-equipped sphygmomanometer, standard managements abiding by the most current guideline will be provided from the responsible physicians. Participants will be given a Bluetooth-equipped sphygmomanometer, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).	Device: Bluetooth-equipped sphygmomanometer Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. (Identical for both intervention and control groups) Every blood pressure and heart rate measured will be encrypted and stored in the main server. (Identical for both intervention and control groups)

Arm

Intervention/Treatment

Experimental: Intensive management arm

Description: Interventions in the intensive management arm consist of 1) behavioral intensification and 2) pharmacological intensification based on olmesartan Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups). Regarding behavioral intensification, an automated texting and call for breakthrough visit will be sent from the main server to encourage regular measurements of BP and maintain a desirable goad of BP. Regarding pharmacological intensification, a specific algorithm for BP-lowering medication prescription will be provided to the responsible physicians by the steering committee.

Behavioral: Behavioral intensification

Suggested algorithm for behavioral intensification: If frequency of BP measurement ≤5 in a week, send a texting message If frequency of BP measurement ≤3 in a week, make a telephone contact by research nurse Target range of home-systolic blood pressure: 110 - 135 If rate of outlier exceeds 50% in a week (based on ≥5 measurements in a week), make a telephone contact by research nurse (applied at least 2 weeks after randomization). A call for breakthrough visit may be issued when clinically required (decided by the institutional investigator) If frequency of BP measurement ≥ 10 in a week and frequency of outlier = 0 in a week, send a texting message to encourage and compliment on excellent BP management

Drug: Pharmacological intensification based on olmesartan

Study drug will be provided from the roll-in period. Step I: Use olmesartan 20 mg only if mean systolic blood pressure ≤150 mm Hg during the immediate past 2 days Use olmesartan 40 mg if mean systolic blood pressure >150 during the immediate past 2 days Step II: olmesartan 20 mg or 40 mg + amlodipine 5 mg Step III: olmesartan 20 mg or 40 mg + amlodipine 10 mg Step IV: olmesartan 20 mg or 40 mg + amlodipine 10 mg + hydrochlorothiazide 12.5 mg If blood pressure profile showed high degree variability to evoke clinical concern, consider discontinuation of hydrochlorothiazide or reduction of olmesartan dose. Use of beta-blockers is permitted if clinically indicated. At each clinic visit regardless of regular or breakthrough visit, follow the pharmacological intensification rule.

Device: Bluetooth-equipped sphygmomanometer

Participants will be given a wireless Bluetooth-equipped sphygmomanometer system, which is connected to the main server through the participants' own smartphone. (Identical for both intervention and control groups) Every blood pressure and heart rate measured will be encrypted and stored in the main server. (Identical for both intervention and control groups)

Active Comparator: Control arm

Description: Other than a bluetooth-equipped sphygmomanometer, standard managements abiding by the most current guideline will be provided from the responsible physicians. Participants will be given a Bluetooth-equipped sphygmomanometer, which is connected to the main server through the participants' own smartphone. Every blood pressure and heart rate measured will be encrypted and stored in the main server (Identical for both intervention and control groups).

Device: Bluetooth-equipped sphygmomanometer

Outcome Measures

Primary Outcome Measures

Recruitment time to prespecified number of subjects [At 3 months after randomization]
Difference in days between recruitment of the first subject and last subject
Retention of included participants [At 3 months after randomization]
Ratio of completed subject over randomized subjects in each group
Frequencies of calls for breakthrough visit [At 3 months after randomization]
Mean and standard deviation of breakthrough visits per each patient in the intensive management group
Rate of patients who responded to the calls for breakthrough visit [At 3 months after randomization]
ratio of subjects response over the breakthrough visit calls
Control of blood pressure [At 3 months after randomization]
ratio of subjects with well-controlled BP in each group

Secondary Outcome Measures

Frequency of out-of-range measurement [At 3 months after randomization]
Frequency of BP measurements out of the desirable BP range in a week
Weighted hit score of BP [At 3 months after randomization]
When two consecutive hits crossed over or below the margin of desirable BP, give 2x weight. Final score will be generated by dividing by total number of measurements
Vascular events [At 3 months after randomization]
Recurrent vascular events including recurrent stroke, myocardial infarction or vascular death
Hypotensive events [Until 3 months after randomization]
Complaint of dizzy spells, falls or low-BP related events by patients

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Ischemic stroke survivors within 7 days after onset
≥19 year-old male or female
Medically and neurologically stabilized enough to take BP-lowering medication
Mean systolic blood pressure ≥135 mm Hg during two days between at least 24 hours after onset and randomization (whether BP-lowering medication was prescribed or not)
Capable of taking oral medication
Capable of operating a wireless Bluetooth-equipped sphygmomanometer system and being expected to follow required procedures of the clinical trial
Patients who provided written informed consent

Exclusion Criteria:

Pregnant, puerperium ≤30 days or on breastfeeding
enrolled in other interventional clinical trial
Being transferred to rehabilitation center or institutionalized
Being expected to have cerebral artery interventions within 3 months after randomization
Known allergic reactions to olmesartan, amlodipine or hydrochlorothiazide
Known severe hepatic disease
Advanced kidney dysfunction requiring dialysis
Being unlikely, in the opinion of the investigator, to comply with the clinical trial protocol or being unsuitable for any other reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam	Gyeonggi	Korea, Republic of	13520
2	Nowon Eulji Medical Center, Eulji University	Seoul		Korea, Republic of	01830
3	Seoul Medical Center	Seoul		Korea, Republic of	02053