Hypertension, Intracerebral Hemorrhage, Stroke
Conditions
Keywords
Cerebral Hemorrhage, Stroke, antihypertensive drugs, blood pressure, disability, clinical trial, outcomes
Brief summary
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.
Detailed description
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.
Interventions
OTHERBlood 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.
Sponsors
National Health and Medical Research Council, Australia
The George Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with CT-confirmed spontaneous Intracerebral Haemorrhage (ICH) * Elevated systolic blood pressure (\>150mmHg and \<220mmHg) * Capacity to commence randomly assigned treatment within 6 hours of onset of ICH. * Able to be 'actively' treated and admitted to a monitored facility
Exclusion criteria
* Clear indication or contraindication to intensive BP lowering. * Evidence ICH secondary to a structural abnormality * Use of thrombolytic agent * 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 * Score of 3-5 on the Glasgow Coma Scale (indicating deep coma) * Significant pre-stroke disability or advanced dementia * Planned early neurological intervention * Participation in another clinical trial. * A high likelihood that the patient will not adhere to the study treatment and follow-up regimen.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| Death at 90 Days | 90 days |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Chile, China, Finland, France, Germany, Hong Kong, India, Italy, Pakistan, Portugal, Spain, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intensive Blood-Pressure Lowering 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.
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. | 1,403 |
| Guideline-Recommended Blood-Pressure Lowering 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.
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. | 1,436 |
| Total | 2,839 |
Baseline characteristics
| Characteristic | Intensive Blood-Pressure Lowering | Total | Guideline-Recommended Blood-Pressure Lowering |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 606 Participants | 1272 Participants | 666 Participants |
| Age, Categorical Between 18 and 65 years | 797 Participants | 1567 Participants | 770 Participants |
| Age, Continuous | 63.0 years STANDARD_DEVIATION 13.1 | 63.5 years STANDARD_DEVIATION 12.9 | 64.1 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment Argentina | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Australia | 33 participants | 73 participants | 40 participants |
| Region of Enrollment Austria | 35 participants | 63 participants | 28 participants |
| Region of Enrollment Belgium | 6 participants | 12 participants | 6 participants |
| Region of Enrollment Brazil | 8 participants | 17 participants | 9 participants |
| Region of Enrollment Chile | 17 participants | 29 participants | 12 participants |
| Region of Enrollment China | 950 participants | 1926 participants | 976 participants |
| Region of Enrollment Finland | 19 participants | 36 participants | 17 participants |
| Region of Enrollment France | 109 participants | 221 participants | 112 participants |
| Region of Enrollment Germany | 70 participants | 141 participants | 71 participants |
| Region of Enrollment Hong Kong | 0 participants | 1 participants | 1 participants |
| Region of Enrollment India | 48 participants | 97 participants | 49 participants |
| Region of Enrollment Italy | 19 participants | 47 participants | 28 participants |
| Region of Enrollment Netherlands | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Norway | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Pakistan | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Portugal | 12 participants | 22 participants | 10 participants |
| Region of Enrollment Spain | 25 participants | 50 participants | 25 participants |
| Region of Enrollment Switzerland | 2 participants | 3 participants | 1 participants |
| Region of Enrollment United Kingdom | 35 participants | 70 participants | 35 participants |
| Region of Enrollment United States | 5 participants | 11 participants | 6 participants |
| Sex: Female, Male Female | 505 Participants | 1059 Participants | 554 Participants |
| Sex: Female, Male Male | 898 Participants | 1780 Participants | 882 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 324 / 1,399 | 329 / 1,430 |
Outcome results
Primary
A Composite of Death or Dependency, With Dependency Being Defined by a Score of 3 to 5 on the Modified Rankin Scale (mRS)
Time frame: 90 days
Population: In the intensive group 12 patients were alive at 90 days but missing data on mRS (required for primary outcome), and 9 patients in the guideline group
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Blood-Pressure Lowering | A Composite of Death or Dependency, With Dependency Being Defined by a Score of 3 to 5 on the Modified Rankin Scale (mRS) | 719 participants |
| Guideline-Recommended Blood-Pressure Lowering | A Composite of Death or Dependency, With Dependency Being Defined by a Score of 3 to 5 on the Modified Rankin Scale (mRS) | 785 participants |
Secondary
Death at 90 Days
Time frame: 90 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intensive Blood-Pressure Lowering | Death at 90 Days | 166 participants |
| Guideline-Recommended Blood-Pressure Lowering | Death at 90 Days | 170 participants |