Blood Pressure Control in Acute Ischemic Stroke

NCT03443596 | Completed Phase 2 DMC

• 1 other identifier: NUSingapore_Vijay
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Blood Pressure; Acute Stroke

Keywords

stroke; blood pressure; hemodynamic

Outcome Measures

Primary Outcomes (1)

• Increase in NIHSS during early intensive BP lowering

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

  within first 72 hours

Secondary Outcomes (2)

• Good functional outcome

  at 90 days

• Ccerebral blood flow reduction during BP control

  within first 72 hours

Study Arms (2)

Early intensive BP control

ACTIVE COMPARATOR

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.

Biological: Early intensive BP control

Guidelined based BP control

NO INTERVENTION

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

Interventions

Early intensive BP control BIOLOGICAL

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

Early intensive BP control

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Although, men and women of reproducible age would be enrolled, all contraception methods would be allowed once they are physically fit.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National University of Singapore: lead

Study Sites (1)

Division of Neurology, National University Hospital

Singapore, 119074, Singapore

Location

Related Publications (1)

• 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.

  PMID: 30290680 DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Vijay K Sharma, MD

  National University Health System, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Allocation of the BP control arm was not disclosed to the study participants
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomized controlled study

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 23, 2018
• Study Start: December 1, 2014
• Primary Completion: March 13, 2019
• Study Completion: March 13, 2019
• Last Updated: April 16, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: by June 2019 and will be available for 1 year
• Access Criteria: if other study has similar protocol. Communicate via email

Locations

SG (1)