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Blood Pressure Control in Acute Ischemic Stroke (BP-Stroke)

Primary Purpose

Blood Pressure, Acute Stroke

Status

Completed

Phase

Phase 2

Locations

Singapore

Study Type

Interventional

Intervention

Early intensive BP control

About this trial

This is an interventional treatment trial for Blood Pressure focused on measuring stroke, blood pressure, hemodynamic

Eligibility Criteria

21 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Disabling neurological deficit (NIHSS minimum 4 points) due to stroke.
IV thrombolysis initiated within 4.5 hours of symptom-onset.
No hemorrhage on baseline non-contrast head CT scan.
At least two consecutive BP measurements (taken at ≥5 min apart) of 160-185mmHg (systolic) and 90 -105mmHg (diastolic) at the time of randomization (BP >185/105mmHg would be treated as standard of care in patient treated with IV-TPA).
Patients between 21-80 years of age, either gender and all ethnicities would be eligible for inclusion. Consent for participation in this study would be obtained from the patient. In patients unable to give consent due to speech or mental disabilities due to stroke, consent would be obtained from the nearest relative.
Although, men and women of reproducible age would be enrolled, all contraception methods would be allowed once they are physically fit.

Exclusion Criteria:

Patients considered ineligible for IV-TPA. Patients treated with mechanical thrombectomy) would not be included.
Symptomatic occlusion or >70% stenosis of the internal carotid artery.
Patients with impaired CVR on TCD. Vasodilatory reserve would be evaluated with the hypercapnoeic challenge (voluntary breath-holding for 30 seconds and monitoring of the mean flow velocities of both MCAs. In patients who are aphasic or unable to hold breath, the hypercapnoeic challenge would consist of subjecting these patients to re-breathe in a closely fit oxygen mask connected with air bag and a capnometer. Our lab has already validated this method against voluntary breath- holding test and acetazolamide challenged SPECT. Patients with an impaired CVR (breath holding index <0.69) would be excluded from the study since this figure is associated with an increased risk of stroke due to cerebral hypoperfusion.
Patients with severe intracranial stenosis.
Conditions requiring urgent antihypertensive treatment independent of BP levels (acute myocardial infarction, severe left ventricular heart failure, aortic dissection, acute renal failure, acute pulmonary oedema and hypertensive encephalopathy)
Functional dependence prior to the acute stroke quantified as a mRS-score of >1.
Contraindications to Labetalol- for example- history of asthma, right-sided congestive heart failure, bradycardia, and heart block.
Patients with contraindications for CT perfusion (like allergy to contrast, renal impairment- serum creatinine >176 µmol/L (2 mg/dL) since creatinine above this level is associated with high risk of contrast induced nephropathy. We will exclude patients with estimated GFR <30ml/minute.
Diabetic patients with normal renal functions would be included. However, we will stop Metformin (if they are receiving it) for 3 days and monitor renal functions.

Sites / Locations

Division of Neurology, National University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Early intensive BP control

Guidelined based BP control

Arm Description

BP in participants in this arm is treated aggressively, lowered and maintained at systolic blood pressure between 140-160mmHg, within 6 hours of stroke onset and maintained in this range for first 72 hours.

Participants are treated according to the current international guidelines in thrombolysed acute ischemic stroke patients, i.e., less than 180/105mmHg

Outcomes

Primary Outcome Measures

Increase in NIHSS during early intensive BP lowering

Proportion of subjects whose NIHSS increases by 4 or more points during active BP reduction.

Secondary Outcome Measures

Good functional outcome

Proportion of subjects achieving modified Rankin score 0-1 in early intensive BP control as compared to the subjects treated with guideline based BP control

Ccerebral blood flow reduction during BP control

Proportion of subjects whose cerebral blood flow on CT perfusion reduces by 20% or more during intensive BP lowering as compared to guideline based approach of BP management in acute ischemic stroke

Full Information

NCT ID

NCT03443596

First Posted

February 2, 2018

Last Updated

April 14, 2019

Sponsor

National University of Singapore

1. Study Identification

Unique Protocol Identification Number

NCT03443596

Brief Title

Blood Pressure Control in Acute Ischemic Stroke

Acronym

BP-Stroke

Official Title

A Randomised Clinical Trial for Evaluating the Safety and Feasibility of Intensive Lowering of Blood Pressure in Acute Ischemic Stroke Patients Treated With Intravenous Thrombolysis

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

December 1, 2014 (Actual)

Primary Completion Date

March 13, 2019 (Actual)

Study Completion Date

March 13, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National University of Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Management of acutely elevated blood pressure during the early phase of ischemic stroke remains controversial. In patients treated with IV-tPA, the risk of ICH is closely related to the BP levels. However, intensive reduction of BP carries a theoretical risk of clinical deterioration by inducing cerebral hypoperfusion. Assessment of cerebral perfusion before and after BP reduction is one of the most scientific method to evaluate the safety (and potential benefits) of BP management in the acute phase of stroke. This project will impact practices and delivery of BP management during the acute phase of ischemic stroke. The findings would aid in designing phase 3 clinical trials will track clinical indicators, including the impact on functional outcomes as well as quality-of-life and cost-effectiveness.

Detailed Description

Specific aims- To determine the tolerability of intensive blood pressure (BP) lowering with intravenous Labetalol infusion (assessed by achieving systolic BP 140-160mmHg range within 6hours of symptom-onset and maintaining it for 72hours post-ictus) in subjects with acute ischemic stroke (AIS) who are treated with intravenous thrombolysis, To quantify the effect of intensive BP lowering on cerebral blood flow (CBF) as measured by computed tomographic (CT) perfusion imaging. To obtain preliminary estimates of clinical impact of intensive BP lowering in acute phase and functional outcomes at 3months. Hypothesis- Investigators hypothesize that early and intensive BP lowering in AIS is safe in patients treated with intravenous tissue plasminogen activator (IV-TPA). Furthermore, such reductions in BP would not produce any significant reduction of CBF on CT perfusion or adversely affect the functional outcomes at 3 months Methodology - AIS patients presenting within 4.5hours of symptom-onset with measurable neurological deficits (NIHSS >4points), treated with intravenous thrombolysis and having elevated BP (systolic BP 160-185mmHg) would be included. In this randomised open label pilot study (with blinded end-point analysis), study participants in target group would receive intravenous Labetalol infusion for 72hours (target systolic BP 140-160mmHg).Close neurological monitoring and serial CT perfusion studies would be performed to evaluate the short-term clinical effects and changes in CBF. Functional outcomes would be evaluated by modified Rankin scale at 3months. Conclusion This pilot randomised study would provide preliminary data about the safety of intensive BP lowering in AIS and form a basis of designing a larger phase III study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Blood Pressure, Acute Stroke

Keywords

stroke, blood pressure, hemodynamic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Randomized controlled study

Masking

Participant

Masking Description

Allocation of the BP control arm was not disclosed to the study participants

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Early intensive BP control

Arm Type

Active Comparator

Arm Description

Arm Title

Guidelined based BP control

Arm Type

No Intervention

Arm Description

Participants are treated according to the current international guidelines in thrombolysed acute ischemic stroke patients, i.e., less than 180/105mmHg

Intervention Type

Biological

Intervention Name(s)

Early intensive BP control

Intervention Description

Participants in the early intensive BP control arm are treated with BP lowering medications, with an aim to bring the systolic BP to 140-160mmHg and maintain this level for 72 hours post-ictus

Primary Outcome Measure Information:

Title

Increase in NIHSS during early intensive BP lowering

Description

Proportion of subjects whose NIHSS increases by 4 or more points during active BP reduction.

Time Frame

within first 72 hours

Secondary Outcome Measure Information:

Title

Good functional outcome

Description

Proportion of subjects achieving modified Rankin score 0-1 in early intensive BP control as compared to the subjects treated with guideline based BP control

Time Frame

at 90 days

Title

Ccerebral blood flow reduction during BP control

Description

Proportion of subjects whose cerebral blood flow on CT perfusion reduces by 20% or more during intensive BP lowering as compared to guideline based approach of BP management in acute ischemic stroke

Time Frame

within first 72 hours

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Disabling neurological deficit (NIHSS minimum 4 points) due to stroke. IV thrombolysis initiated within 4.5 hours of symptom-onset. No hemorrhage on baseline non-contrast head CT scan. At least two consecutive BP measurements (taken at ≥5 min apart) of 160-185mmHg (systolic) and 90 -105mmHg (diastolic) at the time of randomization (BP >185/105mmHg would be treated as standard of care in patient treated with IV-TPA). Patients between 21-80 years of age, either gender and all ethnicities would be eligible for inclusion. Consent for participation in this study would be obtained from the patient. In patients unable to give consent due to speech or mental disabilities due to stroke, consent would be obtained from the nearest relative. Although, men and women of reproducible age would be enrolled, all contraception methods would be allowed once they are physically fit. Exclusion Criteria: Patients considered ineligible for IV-TPA. Patients treated with mechanical thrombectomy) would not be included. Symptomatic occlusion or >70% stenosis of the internal carotid artery. Patients with impaired CVR on TCD. Vasodilatory reserve would be evaluated with the hypercapnoeic challenge (voluntary breath-holding for 30 seconds and monitoring of the mean flow velocities of both MCAs. In patients who are aphasic or unable to hold breath, the hypercapnoeic challenge would consist of subjecting these patients to re-breathe in a closely fit oxygen mask connected with air bag and a capnometer. Our lab has already validated this method against voluntary breath- holding test and acetazolamide challenged SPECT. Patients with an impaired CVR (breath holding index <0.69) would be excluded from the study since this figure is associated with an increased risk of stroke due to cerebral hypoperfusion. Patients with severe intracranial stenosis. Conditions requiring urgent antihypertensive treatment independent of BP levels (acute myocardial infarction, severe left ventricular heart failure, aortic dissection, acute renal failure, acute pulmonary oedema and hypertensive encephalopathy) Functional dependence prior to the acute stroke quantified as a mRS-score of >1. Contraindications to Labetalol- for example- history of asthma, right-sided congestive heart failure, bradycardia, and heart block. Patients with contraindications for CT perfusion (like allergy to contrast, renal impairment- serum creatinine >176 µmol/L (2 mg/dL) since creatinine above this level is associated with high risk of contrast induced nephropathy. We will exclude patients with estimated GFR <30ml/minute. Diabetic patients with normal renal functions would be included. However, we will stop Metformin (if they are receiving it) for 3 days and monitor renal functions.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vijay K Sharma, MD

Organizational Affiliation

National University Health System, Singapore

Official's Role

Principal Investigator

Facility Information:

Facility Name

Division of Neurology, National University Hospital

City

Singapore

ZIP/Postal Code

119074

Country

Singapore

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

We might consider sharing IPD if a study with similar design enters into a meaningful scientific collaboration

IPD Sharing Time Frame

by June 2019 and will be available for 1 year

IPD Sharing Access Criteria

if other study has similar protocol. Communicate via email

Citations:

PubMed Identifier

30290680

Citation

Sharma VK, Tan BYQ, Sim MY, Kulkarni A, Seow PA, Hong CS, Du Z, Wong LYH, Chen J, Chee EYH, Ng BSM, Low Y, Ngiam NJH, Yeo LLL, Teoh HL, Paliwal PR, Rathakrishnan R, Sinha AK, Chan BPL, Butcher K, Anderson CS. Rationale and design of a randomized trial of early intensive blood pressure lowering on cerebral perfusion parameters in thrombolysed acute ischemic stroke patients. Medicine (Baltimore). 2018 Oct;97(40):e12721. doi: 10.1097/MD.0000000000012721.

Results Reference

derived

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Blood Pressure Control in Acute Ischemic Stroke

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