Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)

This study is currently recruiting participants.
Verified August 2013 by The George Institute
Sponsor:
Collaborator:
National Health and Medical Research Council, Australia
Information provided by (Responsible Party):
The George Institute
ClinicalTrials.gov Identifier:
NCT01422616
First received: August 23, 2011
Last updated: August 1, 2013
Last verified: August 2013
  Purpose

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 (140-150 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 symptomatic intracerebral haemorrhage (sICH)?


Condition Intervention Phase
Ischemic Stroke
High Blood Pressure
Drug: Low-dose rtPA
Drug: Standard-dose rtPA
Other: Intensive blood pressure (BP) lowering
Other: BP management policies
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An International Randomised Controlled Trial to Establish the Effects of Low-dose rtPA and the Effects of Early Intensive Blood Pressure Lowering in Patients With Acute Ischaemic Stroke

Resource links provided by NLM:


Further study details as provided by The George Institute:

Primary Outcome Measures:
  • Combined death and any disability [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Modified Rankin Scale [mRS] score 2-6


Secondary Outcome Measures:
  • Symptomatic intracerebral hemorrhage [ Time Frame: 36 hours ] [ Designated as safety issue: Yes ]
    Brain imiging (or necropsy) confirmed ICH with deterioration in NIH Stroke Scale (NIHSS) score

  • Intracerebral hemorrhage of any type in CT scans [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    Intracerebral hemorrhage of any type in CT scans

  • Death or disability by the alternative, but less widely used, shift analysis [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Death or disability by the alternative, but less widely used, shift analysis of scores on the mRS

  • Death [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
  • Disability [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    mRS score 2-5

  • Neurological deterioration [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    deterioration in NIHSS score

  • Health-related quality of life [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Health-related quality of life by the EuroQoL

  • Admission to residential care [ Time Frame: 90 days ] [ Designated as safety issue: No ]
  • Health service use [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Health service use for calculation of resources and costs


Estimated Enrollment: 3300
Study Start Date: March 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Low-dose rtPA
low-dose 0.6 mg/kg (maximum of 90 mg) i.v. rtPA
Drug: Low-dose rtPA
Patients allocated to low-dose will receive 0.6 mg/kg (maximum of 90 mg) i.v. (15% bolus [maximum boluse dose of 9mg] and 85% infusion over 60 mins) recombinant tissue plasminogen activator (rtPA).
Other Name: Actilyse
Active Comparator: Standard-dose rtPA
standard-dose 0.9 mg/kg (maximum of 90 mg) i.v. rtPA
Drug: Standard-dose rtPA
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.
Other Name: Actilyse
Experimental: Early intensive BP lowering

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.

Other: Intensive blood pressure (BP) lowering

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.

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.

Other Names:
  • Labetalol Hydrochloride
  • Metoprolol tartrate
  • Hydralazine Hydrochloride
  • Glycerol Trinitrate
  • Phentolamine mesylate
  • Nicardipine
  • Urapidil
  • Esmolol
  • Clonidine
  • Enalaprilat
  • Niroprusside
Active Comparator: Control / guideline-based BP management

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.

Other: BP management policies

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.

Other Names:
  • Labetalol Hydrochloride
  • Metoprolol tartrate
  • Hydralazine Hydrochloride
  • Glycerol Trinitrate
  • Phentolamine mesylate
  • Nicardipine
  • Urapidil
  • Esmolol
  • Clonidine
  • Enalaprilat
  • Niroprusside

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 5000 patients (3300 for each arm with 60% overlap) with acute ischaemic stroke recruited from over 100+ Clinical Centres from Australia, Asia, Europe and South America.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult (age ≥18 years)
  • A clinical diagnosis of acute ischaemic stroke confirmed by brain imaging
  • Able to receive treatment within 4.5 hours after the definite time of onset of symptoms
  • 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)
  • Provide informed consent (or via an appropriate proxy, according to local requirements)

Specific criteria for arm [A] of low-dose vs standard-dose rtPA:

  • Able to receive either low-dose or standard-dose rtPA

Specific criteria for arm [B] of intensive BP lowering vs guideline recommended BP control

  • Sustained elevated systolic BP level, defined as 2 readings (i.e. ≥150 and ≤185 mmHg
  • Able to receive either immediate intensive BP lowering or conservative BP management

Exclusion Criteria:

  • Unlikely to potentially benefit from the therapy (e.g. advanced dementia) or very high likelihood of death within 24 hours of stroke onset
  • Other medical illness that interferes with outcome assessments and follow-up
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01422616

Contacts
Contact: Hisatomi Arima, MD +61 2 9993 4500 harima@georgeinstitute.org.au

Locations
Australia, New South Wales
Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia, 2050
Contact: Craig S Anderson, MD    +61 2 933 4500    canderson@georgeinstitute.org.au   
Sponsors and Collaborators
The George Institute
National Health and Medical Research Council, Australia
Investigators
Principal Investigator: Craig S Anderson, MD The George Institute
  More Information

No publications provided

Responsible Party: The George Institute
ClinicalTrials.gov Identifier: NCT01422616     History of Changes
Other Study ID Numbers: X11-0123
Study First Received: August 23, 2011
Last Updated: August 1, 2013
Health Authority: Australia: National Health and Medical Research Council

Keywords provided by The George Institute:
Ischemic stroke
High blood pressure
Thrombolysis
Antihypertensive drugs
Disability
Clinical trial

Additional relevant MeSH terms:
Hypertension
Ischemia
Stroke
Cerebral Infarction
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Infarction
Brain Ischemia
Urapidil
Antihypertensive Agents
Metoprolol
Clonidine
Labetalol
Enalaprilat
Enalapril
Hydralazine
Nicardipine
Phentolamine
Esmolol
Metoprolol succinate
Tissue Plasminogen Activator
Glycerol
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014