Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) "ENCHANTED"
Recruiting
Phase 3 Results N/ATrial Description
ENCHANTED is an independent, investigator initiated, international collaborative, quasi-factorial randomised controlled trial involving a package of 2 linked comparative randomised treatment arms, which aims to address 4 key questions in patients eligible for thrombolysis in the acute phase of ischaemic stroke. (1) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) provide equivalent benefits compared to standard-dose (0.9 mg/kg) rtPA? (2) Does intensive blood pressure (BP) lowering (130-140 mmHg systolic target) improve outcomes compared to the current guideline recommended level of BP control (180 mmHg systolic target)? (3) Does low-dose (0.6 mg/kg) intravenous (i.v.) recombinant tissue plasminogen activator (rtPA) reduce the risk of symptomatic intracerebral haemorrhage (sICH)? (4) Does the addition of intensive BP lowering to thrombolysis with rtPA reduce the risk of any intracerebral haemorrhage (ICH)?
Detailed Description
This study is an international, multicentre, prospective, fixed-time point (optional) randomisation for two arms ([A] 'dose of rtPA' and [B] 'level of BP control'), open, blinded endpoint (PROBE), controlled trial that will involve over 4800 patients (3300 for rtPA arm and 2304 for BP arm with 800 overlap) with acute ischaemic stroke recruited from over 100+ Clinical Centres from Australia, Asia, Europe and South America.
Conditions
Interventions
- Low-dose rtPA Drug
Other Names: Actilyse Intervention Desc: Patients allocated to low-dose will receive 0.6 mg/kg (maximum of 60 mg) i.v. (15% bolus [maximum bolus dose of 9mg] and 85% infusion over 60 mins) recombinant tissue plasminogen activator (rtPA). ARM 1: Kind: Experimental Label: Low-dose rtPA - Standard-dose rtPA Drug
Other Names: Actilyse Intervention Desc: Patients allocated to standard-dose will receive 0.9 mg/kg (maximum of 90 mg) i.v. (10% bolus and 90% infusion over 60 mins) rtPA. ARM 1: Kind: Experimental Label: Standard-dose rtPA - BP management policies Other
Other Names: Labetalol Hydrochloride; Metoprolol tartrate; Hydralazine Hydrochloride; Glycerol Trinitrate; Phentolamine mesylate; Nicardipine; Urapidil; Esmolol; Clonidine; Enalaprilat; Niroprusside Intervention Desc: Patients allocated to the control group will receive management of BP that is based on a standard guideline, as published by the AHA. For this group, 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, i.v. treatment may be started until the target systolic BP of 180 mmHg is achieved. 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: Early intensive BP lowering Description: Intensive blood pressure (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). A standardised i.v. BP lowering regimen using locally available and approved i.v. BP lowering agents will be used, commenced in the emergency department and later in a high dependency area (e.g. acute stroke or neurointensive care unit) as is usual for patients receiving rtPA. ARM 2: Kind: Experimental Label: Control / conservative BP management Description: Patients allocated to the control group will receive management of BP that is based on a standard guideline, as published by the AHA. For this group, 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, i.v. treatment may be started until the target systolic BP of 180 mmHg is achieved. ARM 3: Kind: Experimental Label: Control / guideline-based BP management Description: The trial is an assessment of BP lowering management strategies, using routinely available drugs. Patients allocated to the control group will receive management of BP that is based on a standard guideline, as published by the AHA. For this group, 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, i.v. treatment may be started until the target systolic BP of 180 mmHg is achieved. - Intensive blood pressure (BP) lowering Other
Other Names: Labetalol Hydrochloride; Metoprolol tartrate; Hydralazine Hydrochloride; Glycerol Trinitrate; Phentolamine mesylate; Nicardipine; Urapidil; Esmolol; Clonidine; Enalaprilat; Niroprusside Intervention Desc: Intensive blood pressure (BP) lowering to a target systolic BP range 130-140 mmHg within one hour and to maintain this level for at least 72 hours (or until hospital discharge or death if this should occur earlier). A standardised i.v. BP lowering regimen using locally available and approved i.v. BP lowering agents will be used, commenced in the emergency department and later in a high dependency area (e.g. acute stroke or neurointensive care unit) as is usual for patients receiving rtPA. 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: Early intensive BP lowering Description: The trial is an assessment of BP lowering management strategies, using routinely available drugs. Intensive blood pressure (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). A standardised i.v. BP lowering regimen using locally available and approved i.v. BP lowering agents (e.g. Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate, Phentolamine mesylate, Nicardipine, Urapidil, Esmolol, Clonidine, Enalaprilat, Niroprusside) will be used, commenced in the emergency department and later in a high dependency area (e.g. acute stroke or neurointensive care unit) as is usual for patients receiving rtPA.
Trial Design
- Allocation: Randomized
- Masking: Open Label
- Purpose: Treatment
- Endpoint: Safety/Efficacy Study
- Intervention: Factorial Assignment
Outcomes
Type | Measure | Time Frame | Safety Issue |
---|---|---|---|
Primary | Combined death and any disability | 90 days | Yes |
Secondary | Symptomatic intracerebral hemorrhage | 36 hours | Yes |
Secondary | Intracerebral hemorrhage of any type in CT scans | 7 days | Yes |
Secondary | Death or disability by the alternative, but less widely used, shift analysis | 90 days | Yes |
Secondary | Death | 90 days | Yes |
Secondary | Disability | 90 days | Yes |
Secondary | Neurological deterioration | 72 hours | Yes |
Secondary | Health-related quality of life | 90 days | No |
Secondary | Admission to residential care | 90 days | No |
Secondary | Health service use | 90 days | No |
Sponsors
View Trial Locations
Recruitment
- Enrollment: 3,300
- Gender: Both
- Minimum Age: 18 Years
- Accepts Healthy Volunteers: No
- 1 location, 1 country
Principal Investigator
- Craig S Anderson, MD
The George Institute for Global Health