Plain English Summary
Background and study aims
An intracerebral haemorrhage (ICH) occurs when a blood vessel in the brain bursts and bleeds into the brain. ICH is one of the most serious types of stroke, affecting over a million people worldwide each year. About one third of people with ICH die soon after and most survivors are left with major long-term disability. Despite the size of the disease burden and the cost on healthcare resources, there remains uncertainty about the role of surgery and medical treatments for ICH. There is evidence that lowering blood pressure (BP) reduces stroke risk. Although BP levels are commonly high early after the onset of stroke, particularly in ICH, the effects of BP lowering treatment in the acute phase of stroke remain unknown. As a consequence, there are wide ranging guideline recommendations for managing high BP. The aim of this study is to assess the effects of early intensive BP lowering on patients with ICH and high BP, compared with more conservative BP management.
Who can participate?
Patients with acute ICH (within 6 hours of onset) and high BP (between 150 and 220 mmHg).
What does the study involve?
Patients are randomly allocated to either intensive or conservative management of BP. Treatment starts as soon as possible after allocation (e.g., in the emergency department) and is continued in a monitored facility (i.e., intensive care unit, high dependency unit or stroke unit). For patients allocated to the intensive BP lowering group the treatment goal is to achieve BP of less than 140 mmHg within one hour of starting treatment. The second goal is to maintain the BP at 140 mmHg or less or at least 7 days in hospital, and subsequently on discharge and for 90 days. Patients allocated to the conservative BP lowering group receive BP management that is based on American Heart Association (AHA) guidelines. In this group, treatment is started if BP is over 180 mmHg. For both groups, patients must be on an oral blood pressure lowering drug by day 7 or at discharge from hospital, with a long-term target BP of 140 mmHg, as per the guidelines. Information is collected at the time of allocation and follow-up data is collected on four occasions: after 24 hours and 7 days (or at the time of death or hospital discharge, if this should occur before day 7), and after 28 days and 90 days, with the last two assessments carried out either in-person or over the telephone.
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
The George Institute Royal Prince Alfred Hospital (Australia)
When is the study starting and how long is it expected to run for?
September 2008 to December 2012
Who is funding the study?
National Health and Medical Research Council (NHMRC) (Australia)
Who is the main contact?
Prof Craig Anderson
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00716079
Protocol/serial number
NHMRC-571281, ACTRN12608000362392
Study information
Scientific title
An international randomised controlled trial to establish the effects of early intensive blood pressure lowering in patients with intracerebral haemorrhage
Acronym
INTERACT2
Study hypothesis
The purpose of this academic lead study is to determine if a treatment strategy of early intensive blood pressure (BP) lowering compared to conservative BP lowering policy in patients with elevated blood pressure within 6 hours of acute intracerebral haemorrhage (ICH) improves the outcome of death and disability at 3 months after onset.
Ethics approval
SSWAHS Ethics Review Committee (RPAH Zone), 26/06/2008, ref: 08/RPAH/273
Study design
Multicentre treatment parallel-assignment two-armed open-label randomised active-controlled safety/efficacy study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please contact cdelcourt@george.org.au or canderson@george.org.au to request a patient information sheet
Condition
Intracerebral haemorrhage
Intervention
Intensive arm:
Intensive blood pressure (BP) lowering therapy is given via an intravenous drip for 24 hours. The target is to reach a systolic BP less than 140 mmHg within 1 hour.
Conservative arm:
Patients will receive management of BP that is based on a standard guideline, as published by the American Heart Association (AHA). The attending clinician may consider commencing BP treatment if the systolic level is greater than 180 mmHg, however and the first line treatment will be oral (including nasogastric if required) and/or transdermal routes. Should control of systolic BP not be achieved via these routes, intravenous treatment may be started until the target systolic BP of 180 mmHg is achieved.
Intervention:
Blood pressure management policies:
The trial is an assessment of BP lowering management strategies, using routinely available drugs. There is some flexibility in the use of particular BP lowering agents to achieve BP targets.
Intervention type
Drug
Phase
Not Applicable
Drug names
Labetalol hydrochloride, metoprolol tartrate, hydralazine hydrochloride, glycerol trinitrate, phentolamine mesylate, nicardipine, urapidil, esmolol, clonidine, enalaprilat, nitroprusside
Primary outcome measure
A composite of death or dependency, with dependency being defined by a score of 3 to 5 on the Modified Rankin Scale (mRS). Timeframe: 90 days.
Secondary outcome measures
1. Death and dependency in patients treated less than 4 hours
2. Death
3. Dependency
4. Health Related Quality of Life (HRQoL)
5. Physical function
6. Recurrent vascular events
7. Days of hospitalisation
8. Permanent residential care
Timeframe: 90 days
Overall trial start date
01/09/2008
Overall trial end date
31/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients with computed tomography (CT)-confirmed spontaneous intracerebral haemorrhage (ICH)
2. Elevated systolic blood pressure (greater than 150 mmHg and less than 220 mmHg)
3. Capacity to commence randomly assigned treatment within 6 hours of onset of ICH
4. Able to be 'actively' treated and admitted to a monitored facility
5. Male and female, aged older than 18 years old
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
2839
Participant exclusion criteria
1. Clear indication or contraindication to intensive BP lowering
2. Evidence ICH secondary to a structural abnormality
3. Use of thrombolytic agent
4. Previous ischaemic stroke within 30 days
5. A very high likelihood that the patient will die within the next 24 hours on the basis of clinical and/or radiological criteria
6. Score of 3 - 5 on the Glasgow Coma Scale (indicating deep coma)
7. Significant pre-stroke disability or advanced dementia
8. Planned early neurological intervention
9. Participation in another clinical trial
10. A high likelihood that the patient will not adhere to the study treatment and follow-up regimen
Recruitment start date
01/09/2008
Recruitment end date
31/12/2012
Locations
Countries of recruitment
Argentina, Australia, Austria, Belgium, Brazil, Chile, China, Finland, France, Germany, Hong Kong, India, Italy, Netherlands, Norway, Pakistan, Portugal, Spain, Switzerland, United Kingdom, United States of America
Trial participating centre
The George Institute Royal Prince Alfred Hospital
Sydney
2050
Australia
Sponsor information
Organisation
National Health and Medical Research Council (NHMRC) (Australia)
Sponsor details
GPO Box 1421
ACT 2601
Canberra
2601
Australia
+61 (0)1800 500 983
grantnet.help@nhmrc.gov.au
Sponsor type
Research council
Website
Funders
Funder type
Research council
Funder name
National Health and Medical Research Council (NHMRC) (Australia)
Alternative name(s)
NHMRC
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Australia
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
See https://clinicaltrials.gov/ct2/show/results/NCT00716079
Publication list
1. 2008 pilot study results in http://www.ncbi.nlm.nih.gov/pubmed/18396107
2. 2010 protocol in http://www.ncbi.nlm.nih.gov/pubmed/20446945
3. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22129475
4. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23713578
5. 2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24530176
Publication citations
-
Pilot study results
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, , Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial., Lancet Neurol, 2008, 7, 5, 391-399, doi: 10.1016/S1474-4422(08)70069-3.
-
Protocol
Delcourt C, Huang Y, Wang J, Heeley E, Lindley R, Stapf C, Tzourio C, Arima H, Parsons M, Sun J, Neal B, Chalmers J, Anderson C, , The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT2)., Int J Stroke, 2010, 5, 2, 110-116, doi: 10.1111/j.1747-4949.2010.00415.x.
-
Results
Delcourt C, Stapf C, Tzourio C, Héritier S, Anderson C, [The second (main) phase of an open, randomised, multicentre study to investigate the effectiveness of an INTEnsive blood pressure Reduction in Acute Cerebral hemorrhage Trial (INTERACT2): protocol and baseline characteristics of patients included in France]., Rev. Neurol. (Paris), 2012, 168, 4, 321-327, doi: 10.1016/j.neurol.2011.08.010.
-
Results
Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, Lindley R, Robinson T, Lavados P, Neal B, Hata J, Arima H, Parsons M, Li Y, Wang J, Heritier S, Li Q, Woodward M, Simes RJ, Davis SM, Chalmers J, , Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage., N. Engl. J. Med., 2013, 368, 25, 2355-2365, doi: 10.1056/NEJMoa1214609.
-
Results
Manning L, Hirakawa Y, Arima H, Wang X, Chalmers J, Wang J, Lindley R, Heeley E, Delcourt C, Neal B, Lavados P, Davis SM, Tzourio C, Huang Y, Stapf C, Woodward M, Rothwell PM, Robinson TG, Anderson CS, , Blood pressure variability and outcome after acute intracerebral haemorrhage: a post-hoc analysis of INTERACT2, a randomised controlled trial., Lancet Neurol, 2014, 13, 4, 364-373, doi: 10.1016/S1474-4422(14)70018-3.