Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage

Study Overview
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Brief Summary
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The purpose of the study is to determine whether lowering high blood pressure levels after the start of a stroke caused by bleeding in the brain (intracerebral haemorrhage) will reduce the chances of a person dying or surviving with a long term disability. The study will be undertaken in two phases: a vanguard phase in 400 patients, to plan for a main phase in 2000 patients.

Detailed Description
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Intracerebral haemorrhage (ICH) is one of the most serious subtypes of stroke, affecting approximately 2-3 million people worldwide each year. About one third of people with ICH die early after onset and the majority of survivors are left with major long-term disability. Administration of activated recombinant human Factor VII has been shown to limit haematoma expansion in randomised controlled clinical trials; however, future clinical use of this agent may be limited by a short therapeutic time window, contraindication in patients at risk of thromboembolism and high cost. Currently, no acute medical therapies have been shown to alter outcome in ICH and the role of surgery remains uncertain. Blood pressure (BP) levels are strongly and positively associated with the incidence of first and recurrent stroke and there is definite evidence that BP lowering reduces stroke risk. Although BP levels are commonly elevated after stroke onset, particularly in ICH, the effects of BP lowering treatment in the acute phase of stroke remain unknown. The study aims to establish the effectiveness of a management policy of early intensive BP lowering on death & disability in patients with primary ICH compared to current guideline-based management of high BP in the clinical setting.

Official Title
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A Randomised Trial to Establish the Effects of Early Intensive Blood Pressure Lowering on Death and Disability in Patients With Stroke Due to Acute Intracerebral Haemorrhage

Conditions
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CVA (Cerebrovascular Accident), Cerebral Hemorrhage, Intracranial Hemorrhages

Intervention / Treatment
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* Drug: Labetalol Hydrochloride
* Drug: Metoprolol tartrate
* Drug: Hydralazine Hydrochloride
* Drug: Glycerol Trinitrate
* Drug: Phentolamine mesylate
* Drug: Nicardipine
* Drug: Urapidil
* Drug: Esmolol
* Drug: Clonidine
* Drug: Enalaprilat
* Drug: Nitroprusside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years or above Acute stroke due to spontaneous ICH confirmed by clinical history & CT scan At least 2 systolic BP measurements of >/=150mmHg and </=220mmHg, recorded 2 or more minutes apart Able to commence randomly assigned BP lowering regimen within 6 hours of stroke onset Able to be actively treated and admitted to a monitored facility e.g. HDU/ICU/acute stroke unit Exclusion Criteria: Known definite contraindication to an intensive BP lowering regimen Known definite indication for intensive BP lowering regimen as (or more) intensive than the active treatment arm Definite evidence that the ICH is secondary to a structural abnormality in the brain Previous ischaemic stroke within 30 days A very high likelihood that the patient will die within the next 24 hours on the basis of clinical and/or radiological criteria Known advanced dementia or significant pre-stroke disability Concomitant medical illness that would interfere with outcome assessments and follow up Already booked for surgical evacuation of haematoma Previous participation in this trial or current participation in another investigational drug trial A high likelihood that the patient will not adhere to the study treatment and follow up regimen

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Labetalol Hydrochloride|nan|
|Drug: Metoprolol tartrate|nan|
|Drug: Hydralazine Hydrochloride|nan|
|Drug: Glycerol Trinitrate|nan|
|Drug: Phentolamine mesylate|nan|
|Drug: Nicardipine|nan|
|Drug: Urapidil|nan|
|Drug: Esmolol|nan|
|Drug: Clonidine|nan|
|Drug: Enalaprilat|nan|
|Drug: Nitroprusside|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combination death and dependency, according to a 3-6 scores on the modified Rankin Score. |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause and cause-specific early neurological deterioration during the first 72 hours; haematoma expansion & cerebral oedema at 24 & 72 hours; ; functional disability; cognitive function; quality of life; mortality at 1 and 3 months |  | 24 and 72 hours, 1 and 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical Trial, Blood Pressure, CVA (Cerebrovascular Accident)