Clinical trial NCT00226096: Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: CVA (Cerebrovascular Accident)
Cerebral Hemorrhage
Intracranial Hemorrhages
Keywords: Clinical Trial
Blood Pressure
CVA (Cerebrovascular Accident)
Lead sponsor: The George Institute
Sponsor class: OTHER
Collaborators: name: National Health and Medical Research Council, Australia
First posted: 2005-09-26
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility 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 \</=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

Primary outcomes:
measure: Combination death and dependency, according to a 3-6 scores on the modified Rankin Score.
timeFrame: 3 months
Secondary outcomes:
measure: 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
timeFrame: 24 and 72 hours, 1 and 3 months
Other outcomes:
Locations:
city: Concord
country: Australia
facility: Concord Hospital
state: New South Wales
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Perth
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Beijing
country: China
facility: Regional Coordinating Centre: Peking University First Hospital
city: Beijing
country: China
facility: Hospitals in China, c/o The George Institute China
city: Shanghai
country: China
facility: Regional Coordinating Centre: Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Institute of Hypertension, Shanghai Second Medical University
city: Auckland
country: New Zealand
facility: North Shore Hospital
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
Study officials:
affiliation: The George Institute
name: Craig Anderson, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The George Institute
name: Bruce Neal, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Anderson CS, Huang Y, Wang JG, Arima H, Neal B, Peng B, Heeley E, Skulina C, Parsons MW, Kim JS, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Heritier S, Morgenstern LB, Chalmers J; INTERACT Investigators. Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial. Lancet Neurol. 2008 May;7(5):391-9. doi: 10.1016/S1474-4422(08)70069-3. Epub 2008 Apr 7.
citation: Sandset EC, Wang X, Carcel C, Sato S, Delcourt C, Arima H, Stapf C, Robinson T, Lavados P, Chalmers J, Woodward M, Anderson CS. Sex differences in treatment, radiological features and outcome after intracerebral haemorrhage: Pooled analysis of Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trials 1 and 2. Eur Stroke J. 2020 Dec;5(4):345-350. doi: 10.1177/2396987320957513. Epub 2020 Sep 20.
citation: Wang X, Moullaali TJ, Li Q, Berge E, Robinson TG, Lindley R, Zheng D, Delcourt C, Arima H, Song L, Chen X, Yang J, Chalmers J, Anderson CS, Sandset EC. Utility-Weighted Modified Rankin Scale Scores for the Assessment of Stroke Outcome: Pooled Analysis of 20 000+ Patients. Stroke. 2020 Aug;51(8):2411-2417. doi: 10.1161/STROKEAHA.119.028523. Epub 2020 Jul 9.
citation: Wang X, Sandset EC, Moullaali TJ, Chen G, Song L, Carcel C, Delcourt C, Woodward M, Robinson T, Chalmers J, Arima H, Anderson CS; INTERACT2 Investigators. Determinants of the high admission blood pressure in mild-to-moderate acute intracerebral hemorrhage. J Hypertens. 2019 Jul;37(7):1463-1466. doi: 10.1097/HJH.0000000000002056.
citation: Chen R, Wang X, Anderson CS, Robinson T, Lavados PM, Lindley RI, Chalmers J, Delcourt C. Infratentorial Intracerebral Hemorrhage. Stroke. 2019 May;50(5):1257-1259. doi: 10.1161/STROKEAHA.118.023766.
citation: Delcourt C, Zheng D, Chen X, Hackett M, Arima H, Hata J, Heeley E, Al-Shahi Salman R, Woodward M, Huang Y, Robinson T, Lavados PM, Lindley RI, Stapf C, Davies L, Chalmers J, Anderson CS, Sato S; INTERACT Investigators. Associations with health-related quality of life after intracerebral haemorrhage: pooled analysis of INTERACT studies. J Neurol Neurosurg Psychiatry. 2017 Jan;88(1):70-75. doi: 10.1136/jnnp-2016-314414. Epub 2016 Oct 21.
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citation: Qiu M, Sato S, Zheng D, Wang X, Carcel C, Hirakawa Y, Sandset EC, Delcourt C, Arima H, Wang J, Chalmers J, Anderson CS; INTERACT Investigators*. Admission Heart Rate Predicts Poor Outcomes in Acute Intracerebral Hemorrhage: The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial Studies. Stroke. 2016 Jun;47(6):1479-85. doi: 10.1161/STROKEAHA.115.012382. Epub 2016 May 10.
citation: Moullaali TJ, Sato S, Wang X, Rabinstein AA, Arima H, Carcel C, Chen G, Robinson T, Heeley E, Chan E, Delcourt C, Stapf C, Cordonnier C, Lindley RI, Chalmers J, Anderson CS; INTERACT Investigators. Prognostic significance of delayed intraventricular haemorrhage in the INTERACT studies. J Neurol Neurosurg Psychiatry. 2017 Jan;88(1):19-24. doi: 10.1136/jnnp-2015-311562. Epub 2016 Jan 8.
citation: Wang X, Arima H, Al-Shahi Salman R, Woodward M, Heeley E, Stapf C, Lavados PM, Robinson T, Huang Y, Wang J, Delcourt C, Anderson CS. Rapid Blood Pressure Lowering According to Recovery at Different Time Intervals after Acute Intracerebral Hemorrhage: Pooled Analysis of the INTERACT Studies. Cerebrovasc Dis. 2015;39(3-4):242-8. doi: 10.1159/000381107. Epub 2015 Mar 25.
citation: Yang J, Arima H, Wu G, Heeley E, Delcourt C, Zhou J, Chen G, Wang X, Zhang S, Yu S, Chalmers J, Anderson CS; INTERACT Investigators. Prognostic significance of perihematomal edema in acute intracerebral hemorrhage: pooled analysis from the intensive blood pressure reduction in acute cerebral hemorrhage trial studies. Stroke. 2015 Apr;46(4):1009-13. doi: 10.1161/STROKEAHA.114.007154. Epub 2015 Feb 24.
citation: Priglinger M, Arima H, Anderson C, Krause M; INTERACT Investigators. No relationship of lipid-lowering agents to hematoma growth: pooled analysis of the intensive blood pressure reduction in acute cerebral hemorrhage trials studies. Stroke. 2015 Mar;46(3):857-9. doi: 10.1161/STROKEAHA.114.007664. Epub 2015 Feb 5.
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citation: Wang X, Arima H, Al-Shahi Salman R, Woodward M, Heeley E, Stapf C, Lavados PM, Robinson T, Huang Y, Wang J, Delcourt C, Anderson CS; INTERACT Investigators. Clinical prediction algorithm (BRAIN) to determine risk of hematoma growth in acute intracerebral hemorrhage. Stroke. 2015 Feb;46(2):376-81. doi: 10.1161/STROKEAHA.114.006910. Epub 2014 Dec 11.
citation: Delcourt C, Huang Y, Arima H, Chalmers J, Davis SM, Heeley EL, Wang J, Parsons MW, Liu G, Anderson CS; INTERACT1 Investigators. Hematoma growth and outcomes in intracerebral hemorrhage: the INTERACT1 study. Neurology. 2012 Jul 24;79(4):314-9. doi: 10.1212/WNL.0b013e318260cbba. Epub 2012 Jun 27.
citation: Arima H, Huang Y, Wang JG, Heeley E, Delcourt C, Parsons M, Li Q, Neal B, Chalmers J, Anderson C; INTERACT1 Investigators. Earlier blood pressure-lowering and greater attenuation of hematoma growth in acute intracerebral hemorrhage: INTERACT pilot phase. Stroke. 2012 Aug;43(8):2236-8. doi: 10.1161/STROKEAHA.112.651422. Epub 2012 Jun 7.
citation: Arima H, Anderson CS, Wang JG, Huang Y, Heeley E, Neal B, Woodward M, Skulina C, Parsons MW, Peng B, Tao QL, Li YC, Jiang JD, Tai LW, Zhang JL, Xu E, Cheng Y, Morgenstern LB, Chalmers J; Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial Investigators. Lower treatment blood pressure is associated with greatest reduction in hematoma growth after acute intracerebral hemorrhage. Hypertension. 2010 Nov;56(5):852-8. doi: 10.1161/HYPERTENSIONAHA.110.154328. Epub 2010 Sep 7.