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.
Intracerebral haemorrhage (ICH) is one of the most serious subtypes of stroke, affecting over a million people worldwide each year, most of whom live in Asia. About one third of people with ICH die early after onset and the majority of survivors are left with major long-term disability. Despite the magnitude of the disease burden and cost on healthcare resources, there remains uncertainty about the role of surgery for ICH and no acute medical therapies have been shown to definitely alter outcome in ICH.
The INTERACT2 study follows the recently completed initial pilot study vanguard phase) which established the feasibility of the protocol, safety of early intensive BP lowering, and effects on haematoma expansion within 6 hours of onset of ICH. Having established 'proof-of-concept' that BP lowering may improve outcome by reducing haematoma expansion, INTERACT2 aims to establish the effects of the treatment on major clinical endpoints in patients with ICH recruited from an expanding clinical network around the world.
- Antihypertensives Drug
Intervention Desc: This category includes all BP lowering drugs in stroke prevention trials
- Blood pressure management policies Other
Other Names: Labetalol Hydrochloride; Metoprolol tartrate; Hydralazine Hydrochloride; Glycerol Trinitrate; Phentolamine mesylate; Nicardipine; Urapidil; Esmolol; Clonidine; Enalaprilat; nitroprusside Intervention Desc: 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. ARM 1: Kind: Experimental Label: Intensive Description: Intensive Blood pressure (BP) lowering therapy is given via an intravenous drip for 24 hours. The target is to reach a systolic BP <140mmHg within 1 hour. ARM 2: Kind: Experimental Label: Conservative Description: 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. ARM 3: Kind: Experimental Label: Intensive BP lowering Description: Management policy to lower the systolic Blood pressure (BP) to a target of 140mmHg within 1 hour of randomization and sustained for 24 hours. Sites were provided with protocols for different intravenous agents and used whichever routinely available drugs were in their hospital. ARM 4: Kind: Experimental Label: Guideline recommended BP lowering Description: Patients received management of BP based on the standard guidelines at the time, as published by the American Heart Association (AHA) in 2007 and 2010. 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.
- Allocation: Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Parallel Assignment
Participants will be randomized to either early intensive blood pressure lowering using intravenous drugs during the first 24 hours, or blood pressure management according to current American Heart Association guidelines. Clinical outcomes will be assessed over 90 days.
|Type||Measure||Time Frame||Safety Issue|
|Primary||Combination death and dependency, according to a 3-6 scores on the modified Rankin Score.|
|Secondary||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|
|Primary||A composite of death or dependency, with dependency being defined by a score of 3 to 5 on the modified Rankin Scale (mRS)||90 days||Yes|
|Secondary||death and dependency in patients treated <4 hours; death; dependency; HRQoL; physical function; recurrent vascular events; days of hospitalisation; permanent residential care||90 days||Yes|
|Secondary||Death at 90 Days||90 days||No|