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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01422616




Registration number
NCT01422616
Ethics application status
Date submitted
23/08/2011
Date registered
24/08/2011

Titles & IDs
Public title
Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)
Scientific 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
Secondary ID [1] 0 0
X11-0123
Universal Trial Number (UTN)
Trial acronym
ENCHANTED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischemic Stroke 0 0
High Blood Pressure 0 0
Condition category
Condition code
Stroke 0 0 0 0
Haemorrhagic
Stroke 0 0 0 0
Ischaemic
Cardiovascular 0 0 0 0
Hypertension
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Low-dose rtPA
Treatment: Drugs - Standard-dose rtPA
Other interventions - Intensive blood pressure (BP) lowering
Other interventions - BP management policies

Experimental: Low-dose rtPA (Recruitment completed in August 2015) - low-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA

Active comparator: Standard-dose rtPA (Recruitment completed in August 2015) - standard-dose 0.9 mg/kg (maximum of 90 mg) i.v. rtPA

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 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 (e.g. Labetalol Hydrochloride, Metoprolol tartrate, Hydralazine Hydrochloride, Glycerol Trinitrate, Phentolamine mesylate, Nicardipine, Urapidil, Esmolol, Clonidine, Enalaprilat, Nitroprusside) 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.

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 American Heart Association (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.


Treatment: Drugs: Low-dose rtPA
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).

Treatment: Drugs: 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 interventions: Intensive blood pressure (BP) lowering
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.

Other interventions: 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.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Combined death and disability
Timepoint [1] 0 0
90 days
Secondary outcome [1] 0 0
Symptomatic intracerebral hemorrhage
Timepoint [1] 0 0
36 hours
Secondary outcome [2] 0 0
Symptomatic intracerebral hemorrhage
Timepoint [2] 0 0
36 hours
Secondary outcome [3] 0 0
Death or disability by the alternative, ordinal shift analysis
Timepoint [3] 0 0
90 days
Secondary outcome [4] 0 0
Death
Timepoint [4] 0 0
at 7 and 90 days
Secondary outcome [5] 0 0
Disability
Timepoint [5] 0 0
90 days
Secondary outcome [6] 0 0
Neurological deterioration
Timepoint [6] 0 0
72 hours
Secondary outcome [7] 0 0
Health-related quality of life
Timepoint [7] 0 0
90 days
Secondary outcome [8] 0 0
Admission to residential care
Timepoint [8] 0 0
90 days
Secondary outcome [9] 0 0
Health service use
Timepoint [9] 0 0
90 days
Secondary outcome [10] 0 0
Symptomatic intracerebral hemorrhage (ICH)
Timepoint [10] 0 0
within 7 days
Secondary outcome [11] 0 0
Any intracerebral hemorrhage (ICH)
Timepoint [11] 0 0
any time during 90 days
Secondary outcome [12] 0 0
Death or disability in as treated per-protocol population
Timepoint [12] 0 0
90 days
Secondary outcome [13] 0 0
Death or disability in as treated per-protocol population
Timepoint [13] 0 0
90 days
Secondary outcome [14] 0 0
Death or neurological deterioration
Timepoint [14] 0 0
72 hours
Secondary outcome [15] 0 0
Length of initial acute hospital stay
Timepoint [15] 0 0
within 90 days
Secondary outcome [16] 0 0
Recurrent acute myocardial infarction and ischemic stroke
Timepoint [16] 0 0
within 90 days

Eligibility
Key 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
* Provide informed consent (or via an appropriate proxy, according to local requirements)

Specific criteria for arm [A] of low-dose vs standard-dose rtPA (Recruitment completed in August 2015.):

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

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

* Patient will or has received thrombolysis treatment with rtPA, either randomised dose within the trial or physician decided dose rtPA outside of the trial
* Sustained elevated systolic BP level, defined as 2 readings = 150 mmHg
* Able to commence intensive BP lowering treatment within 6 hours of stroke onset
* Able to receive either immediate intensive BP lowering or conservative BP management
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Unlikely to potentially benefit from the therapy (e.g. advanced dementia), or a very high likelihood of death within 24 hours of stroke onset.
* Other medical illness that interferes with outcome assessments and follow-up [known significant pre-stroke disability (mRS scores 2-5)].
* Specific contraindications to rtPA (Actilyse) or any of the blood pressure agents to be used.
* Participation in another clinical trial involving evaluation of pharmacological agents.
* Need for following concomitant medication, including phosphodiesterase inhibitors and monoamine oxidase inhibitors.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2018
Sample size
Target
Accrual to date
Final
4587
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2050 - Sydney

Funding & Sponsors
Primary sponsor type
Other
Name
The George Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
National Health and Medical Research Council, Australia
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
The Stroke Association, United Kingdom
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/industry
Name [4] 0 0
Takeda
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Craig S Anderson, MD
Address 0 0
The George Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Data sharing upon approval through formal application to the Research Office of The George Institute for Global Health, Australia

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
available
Available to whom?
approved protocol, ethics committee and data sharing agreement
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents



Results not provided in https://clinicaltrials.gov/study/NCT01422616