Blood Pressure Control in Acute Ischemic Stroke
Blood Pressure Control in Acute Ischemic Stroke
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.
Specific aims-

 1. 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,

 2. To quantify the effect of intensive BP lowering on cerebral blood flow (CBF) as measured
 by computed tomographic (CT) perfusion imaging.

 3. 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.
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.