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ISRCTN
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ISRCTN82387104
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ClinicalTrials.gov identifier
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NCT01422616
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Public title
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ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy
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Scientific title
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ENhanced Control of Hypertension ANd Thrombolysis strokE stuDy: a multicentre randomised trial
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Acronym
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ENCHANTED
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Serial number at source
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X11 - 0123 & HREC/11/RPAH/176
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Study hypothesis
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In patients with acute ischaemic stroke eligible for thrombolysis with recombinant tissue plasminogen activator (rtPA) according to local guidelines and otherwise able to receive best usual medical care, the primary aims are to determine:
1. Whether compared to the standard dose, low-dose rtPA is at least as effective (‘not inferior’) on death or any disability (i.e. null hypothesis is that low-dose is inferior to standard dose rtPA)
2. Whether compared with current guideline recommended criteria for blood pressure (BP) management, early intensive BP lowering is superior in reducing the risk of death or any disability (i.e. null hypothesis is that there is no difference in the intensities of BP control on this outcome).
The key secondary aims is to determine
1. Whether compared with standard dose rtPA, low-dose rtPA reduces the risk of Symptomatic Intra-Cerebral Hemorrhage (sICH)
2. Whether compared with standard guideline-based BP management, early intensive BP lowering after rtPA reduces the risk of sICH (i.e. null hypothesis is that there is no difference in the rate of sICH between groups of differing intensities of BP lowering). Other secondary aims are to define the effects of the treatments on any ICH; a shift (‘improvement’) in disability according to the modified Rankin Scale (mRS); separately on death and disability; early neurological deterioration; health-related quality of life (HRQoL); recurrent stroke and myocardial infarction; length of hospital stay; and need for permanent residential care.
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Lay summary
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Lay summary under review
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Ethics approval
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Sydney South West Area Health Service Ethics Review Committee (RPAH Zone), Approval date: 7 June 2011 , Reference: X11 - 0123 & HREC/11/RPAH/176
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Study design
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International multicentre prospective fixed-time point randomisation for two arms open blinded endpoint controlled trial
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Countries of recruitment
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Argentina, Australia, Austria, Belgium, Brazil, Chile, China, Colombia, France, Germany, Greece, Hong Kong, Italy, Korea, South, Norway, Portugal, Singapore, Spain, Sri Lanka, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, Viet Nam
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Disease/condition/study domain
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Acute Ischaemic Stoke
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Participants - inclusion criteria
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1. General criteria for use of thrombolytic treatment with rtPA
1.1. Adult (age ≥18 years)
1.2. A clinical diagnosis of acute ischaemic stroke confirmed by brain imaging
1.3. Able to receive treatment within 4.5 hours after the definite time of onset of symptoms
1.4. Have a systolic BP ≤185 mmHg (i.e. the guideline recommended level of eligibility for rtPA; patients with higher BP levels at presentation can still be included provided the BP is reduced to the entry level prior to commencement of the randomised treatment).
1.5. Provide informed consent (or via an appropriate proxy, according to local requirements)
2. Specific criteria for arm [A] of low-dose vs standard-dose rtPA.
2.1. No definite indication nor contraindication for either low-dose or standard-dose rtPA.
3. Specific criteria for arm [B] of intensive BP lowering vs guideline recommended BP control
3.1. Sustained elevated systolic BP level, defined as 2 readings ≥150 and ≤185 mmHg (i.e. the upper level for contraindication to use of thrombolysis)
3.2. No definite indication or contraindication to either immediate "intensive‟ BP lowering (to a target of 140-150 mmHg systolic) versus guideline-based BP control (e.g. intensive BP lowering is feasible and does not appear to pose excessive hazard to the patient).
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Participants - exclusion criteria
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Patients will not be eligible if there is one or more of the following:
1. Unlikely to potentially benefit from the therapy (e.g. advanced dementia, known severe pre-stroke disability (mRS scores 3-5), or a very high likelihood of death within 24 hours of stroke onset
2. Other medical illness that interferes with outcome assessments and follow-uP
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Anticipated start date
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30/11/2011
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Anticipated end date
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30/11/2016
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Status of trial
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Ongoing |
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Patient information material
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Not available in web format, please use the contact details below to request a patient information sheet
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Target number of participants
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5000
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Interventions
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Randomised interventions: Randomisation is via a central internet-based system developed by The George Institute, Sydney, Australia, either direct or via a specially developed IVRS (only in China), stratified by country, site, time from onset (<3 vs ≥3 hours) and NIH Stroke Scale (NIHSS) (<10 vs ≥10) to ensure balance in key prognostic factors. Most patients will be eligible for arm [A] as the overall inclusion criteria is eligibility for rtPA, but only a proportion (~60%) of patients with acute ischaemic stroke are anticipated to have elevated blood pressure (BP) and thus eligible for arm [B]. Investigators have the choice of randomising patients into, one or both treatment arms: [A]: standard-dose 0.9 mg/kg (maximum of 90 mg) or low-dose 0.6 mg/kg (maximum of 90 mg) i.v. rtPA (Actilyse) and/or [B]: intensive BP lowering to a target systolic BP range 140-150 mmHg within 30 minutes of rtPA and to maintain this level for at least 72 hours (or until hospital discharge or death if this should occur earlier) or guideline-based BP lowering to a target systolic BP of <180 mmHg post-rtPA. Standardised locally approved i.v. BP lowering agents are to be used.
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Primary outcome measure(s)
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1. Compared with standard dose i.v. rtPA, low-dose rtPA is at least as effective („not inferior‟) on the major clinical outcome of death or any disability at 3 months (i.e. corresponding null hypothesis is that low-dose is inferior to standard dose rtPA);
2. Compared with standard guideline-based BP management, early intensive BP lowering is superior in reducing the risk of the major clinical outcome of death or any disability at 3 months (i.e. corresponding null hypothesis is that there is no difference in treatments on this outcome)
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Secondary outcome measure(s)
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1. Compared with standard dose i.v. rtPA, low-dose rtPA reduces the risk of sICH
2. Compared with standard guideline-based BP management, early intensive BP lowering after thrombolysis with rtPA reduces the risk of sICH (i.e. corresponding null hypothesis is that there is no difference in the rate of sICH between groups of differing intensities of BP lowering).
3. To define effects on a shift („improvement‟) in measures of disability:
3.1. According to the grading system on the modified Rankin Scale (mRS)
3.2. Any ICH; separately on death and disability
3.3. Physical function
3.4. Early neurological deterioration
3.5. HRQoL
3.6. Major vascular events of recurrent stroke and myocardial infarction
3.7. Length of hospital stay
3.8. Need for permanent residential care and
3.9. Health care costs
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Sources of funding
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Australian National Health Service and Medical Research Council (Australia)
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Trial website
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Publications
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Contact name
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Prof
Craig
Anderson
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Address
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The George Institute for Global Health
Street: Level 10, King George V Building
Missenden Road, Royal Prince Alfred Hospital
Mail: PO Box M201, Missenden Road
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City/town
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Sydney
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Zip/Postcode
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2217
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Country
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Australia
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Sponsor
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The George Institute for Global Health (Australia)
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Address
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c/o Sully Fuentes
Street: Level 10, King George V Building
Missenden Road, Royal Prince Alfred Hospital
Mail: PO Box M201, Missenden Road
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City/town
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Sydney
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Zip/Postcode
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2217
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Country
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Australia
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Date applied
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28/10/2011
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Last edited
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04/11/2011
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Date ISRCTN assigned
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04/11/2011
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