Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage

Condition(s) targeted: CVA (Cerebrovascular Accident); Cerebral Hemorrhage; Intracranial Hemorrhages

Intervention: 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 (Drug)

Phase: N/A

Status: Completed

Sponsored by: The George Institute

Official(s) and/or principal investigator(s):
Craig Anderson, PhD, Principal Investigator, Affiliation: The George Institute
Bruce Neal, PhD, Principal Investigator, Affiliation: The George Institute

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.

Official title: 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Combination death and dependency, according to a 3-6 scores on the modified Rankin Score.

Secondary outcome: 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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 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

Hospitals in China, c/o The George Institute China, Beijing, China

Regional Coordinating Centre: Peking University First Hospital, Beijing 100034, China

Regional Coordinating Centre: Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Second Medical University, Shanghai 200025, China

North Shore Hospital, Auckland, New Zealand

Christchurch Hospital, Christchurch, New Zealand

Concord Hospital, Concord, New South Wales 2138, Australia

Gosford Hospital, Gosford, New South Wales 2250, Australia

St George Hospital, Kogarah, New South Wales 2217, Australia

John Hunter Hospital, Newcastle, New South Wales 2310, Australia

Royal Prince Alfred Hospital, Sydney, New South Wales 2050, Australia

St Vincent's Hospital, Sydney, New South Wales 2010, Australia

Westmead Hospital, Westmead, New South Wales 2145, Australia

Royal Adelaide Hospital, Adelaide, South Australia 5000, Australia

Alfred Hospital, Melbourne, Victoria 3181, Australia

Austin Health, Melbourne, Victoria, Australia

Box Hill Hospital, Melbourne, Victoria 3128, Australia

Monash Medical Centre, Melbourne, Victoria, Australia

Royal Melbourne Hospital, Melbourne, Victoria 3050, Australia

St Vincent's Hospital, Melbourne, Victoria 3065, Australia

Sir Charles Gairdner Hospital, Perth, Western Australia 6009, Australia

For further information please see The George Institute for International health's website.

Starting date: November 2005
Last updated: June 25, 2008