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

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

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

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

Study Overview

• Status: Completed
• Conditions: Hypertension; Ischemic Stroke
• Intervention / Treatment: Behavioral: Behavioral intensification; Drug: Pharmacological intensification based on olmesartan; Device: Bluetooth-equipped sphygmomanometer

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 Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 01830
    • Nowon Eulji Medical Center, Eulji University
  • Seoul, Korea, Republic of, 02053
    • Seoul Medical Center
  • Gyeonggi
    • Seongnam, Gyeonggi, Korea, Republic of, 13520
      • Seoul National University Bundang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 daysUse 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of out-of-range measurement	Frequency of BP measurements out of the desirable BP range in a week	At 3 months after randomization
Weighted hit score of BP	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	At 3 months after randomization
Vascular events	Recurrent vascular events including recurrent stroke, myocardial infarction or vascular death	At 3 months after randomization
Hypotensive events	Complaint of dizzy spells, falls or low-BP related events by patients	Until 3 months after randomization

Collaborators and Investigators

• Sponsor: Seoul National University Bundang Hospital
• Collaborators: Daiichi Sankyo Korea Co., Ltd.
• Investigators: Principal Investigator: Hee-Joon Bae, MD.PhD, Seoul National University Bundang Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2016
• Primary Completion (ACTUAL): December 7, 2017
• Study Completion (ACTUAL): December 7, 2017

Study Registration Dates

• First Submitted: January 3, 2017
• First Submitted That Met QC Criteria: January 16, 2017
• First Posted (ESTIMATE): January 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 6, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: behavioral intervention; prespecified medication algorithm; bluetooth-equipped sphygmomanometer
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Olmesartan
• Other Study ID Numbers: B-1604/343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED