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Trial registered on ANZCTR


Registration number
ACTRN12611000236998
Ethics application status
Approved
Date submitted
2/03/2011
Date registered
3/03/2011
Date last updated
2/07/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
Enhanced control of hypertension and thrombolysis stroke study
Scientific title
An international randomised controlled trial to compare the effects of low- and standard-dose recombinant tissue plasminogen activator (rtPA) and to establish the effects of early intensive blood pressure (BP) lowering on death and disability in patients with ischaemic stroke
Secondary ID [1] 259718 0
NIl
Universal Trial Number (UTN)
Nil
Trial acronym
ENCHANTED
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 261297 0
Hypertension 261307 0
Condition category
Condition code
Stroke 259445 259445 0 0
Ischaemic
Cardiovascular 259455 259455 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
ENCHANTED is a package of 2 linked randomised controlled trials, arms [A] and [B]. Patients will be included in arm [A] only, arm [B] only, or both arms [A] and [B], based on their eligibility and attending clinician’s level of uncertainty as to the balance of benefits and risks of the investigative treatments in an individual patient.
Patients included in arm [A] will be randomised to receive low-dose 0.6 mg/kg (15% bolus and 85% infusion over 60 minutes) or standard-dose 0.9 mg/kg (10% bolus and 90% infusion over 60 minutes) i.v. rtPA (Actylise).
Patients included in arm [B] will be randomised to receive intensive 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) or guideline-based BP lowering to a target systolic BP of <180 mmHg post-rtPA. Standardised locally approved i.v. BP lowering agents such as clevidipine, labetolol hydrochloride, metoprolol tartrate, hydralazine hydrochloride, glyceral trinitrate and phentoloamine are to be used.
Patients included only in arm [B] are eligible if they receive non-study i.v. rtPA (Actylise) as usual care.
Intervention code [1] 264144 0
Treatment: Drugs
Comparator / control treatment
Usual care (Arm [A]: standard-dose 0.9 mg/kg i.v. rtPA (Actylise). Arm [B]: guideline-based BP lowering.)
Control group
Active

Outcomes
Primary outcome [1] 262251 0
death and any disability (modified Rankin Scale [mRS] score 2-6)
Timepoint [1] 262251 0
90 days
Secondary outcome [1] 273390 0
symptomatic intracerebral haemorrhage (confirmed by CT [or necropsy] with deterioration in NIH Stroke Scale [NIHSS] score)
Timepoint [1] 273390 0
36 hours
Secondary outcome [2] 273391 0
any intracerebral haemorrhage in CT scans
Timepoint [2] 273391 0
7 days
Secondary outcome [3] 273392 0
death or disability by shift analysis of scores on modified Rankin Scale (mRS)
Timepoint [3] 273392 0
90 days
Secondary outcome [4] 273393 0
death
Timepoint [4] 273393 0
90 days
Secondary outcome [5] 273394 0
disability (modified Rankin Scale [mRS] score 2-5)
Timepoint [5] 273394 0
90 days
Secondary outcome [6] 273395 0
neurological deterioration (deterioration in NIH Stroke Scale [NIHSS] score and/or Glasgow Coma Scale [GCS] score)
Timepoint [6] 273395 0
72 hours
Secondary outcome [7] 273396 0
health-related quality of life by the EuroQoL
Timepoint [7] 273396 0
90 days
Secondary outcome [8] 273397 0
admission to residential care by in-person or telephone follow-up
Timepoint [8] 273397 0
90 days
Secondary outcome [9] 273398 0
health service including length of initial hospital stay, re-admission to hospital, visits to outpatient clinics, and visits to primary care physicians obtained by in-person or telephone follow-up
Timepoint [9] 273398 0
90 days

Eligibility
Key inclusion criteria
Patients with clinical diagnosis of acute ischaemic stroke confirmed by brain imaging within 4.5 hours of onset who fulfill local criteria for use of i.v. rtPA are potentially eligible if they have a sustained systolic BP level of 185 mmHg or below.
The attending clinician is required to sequentially consider their level of clinical uncertainty over the balance of potential benefits and risks pertaining to the appropriate dose of rtPA and the level of BP control in each particular patient, as outlined below.
Arm [A]: no definite indication/contraindication for either dose of rtPA; and able to pay for a 50mg vial of rtPA if in a fee-paying health system.
Arm [B]: 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
Gender
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)
Patients are randomised via a central internet-based system developed by The George Institute, Sydney, Australia, either direct or via a specially developed IVRS (only in China).
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 BP and thus eligible for arm [B]. Investigators have the choice of randomising patients into 1 or 2 treatment arms.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Assignment to a treatment group is determined by a computerised algorithm which runs on the central database and uses the minimisation method. The stratification factors are country, site, time from onset (<3 vs 3 hours or longer) and NIHSS (<10 vs 10 or more).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
ENCHANTED is a package of 2 linked randomised controlled trials, arms [A] and [B]. Patients will be included in arm [A] only, arm [B] only, or both arms [A] and [B], based on their eligibility and attending clinician’s level of uncertainty as to the balance of benefits and risks of the investigative treatments in an individual patient.
Phase
Phase 3 / Phase 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment postcode(s) [1] 3734 0
2010
Recruitment postcode(s) [2] 3735 0
2050
Recruitment postcode(s) [3] 3736 0
2065
Recruitment postcode(s) [4] 3737 0
2138
Recruitment postcode(s) [5] 3738 0
2145
Recruitment postcode(s) [6] 3739 0
2217
Recruitment postcode(s) [7] 3740 0
2305
Recruitment postcode(s) [8] 3741 0
2250
Recruitment postcode(s) [9] 3742 0
2606
Recruitment postcode(s) [10] 3743 0
3004
Recruitment postcode(s) [11] 3744 0
3050
Recruitment postcode(s) [12] 3745 0
3065
Recruitment postcode(s) [13] 3746 0
3084
Recruitment postcode(s) [14] 3747 0
3128
Recruitment postcode(s) [15] 3748 0
3168
Recruitment postcode(s) [16] 3749 0
4029
Recruitment postcode(s) [17] 3750 0
5000
Recruitment postcode(s) [18] 3751 0
5011
Recruitment postcode(s) [19] 3752 0
5042
Recruitment postcode(s) [20] 3753 0
6009
Recruitment outside Australia
Country [1] 3265 0
Hong Kong
State/province [1] 3265 0
Country [2] 3266 0
United Kingdom
State/province [2] 3266 0
Country [3] 3267 0
France
State/province [3] 3267 0
Country [4] 3268 0
Austria
State/province [4] 3268 0
Country [5] 3269 0
Swaziland
State/province [5] 3269 0
Country [6] 3270 0
Italy
State/province [6] 3270 0
Country [7] 3271 0
Portugal
State/province [7] 3271 0
Country [8] 3272 0
Spain
State/province [8] 3272 0
Country [9] 3273 0
China
State/province [9] 3273 0
Country [10] 3274 0
New Zealand
State/province [10] 3274 0
Country [11] 3275 0
Singapore
State/province [11] 3275 0
Country [12] 3276 0
Korea, Republic Of
State/province [12] 3276 0
Country [13] 3277 0
Viet Nam
State/province [13] 3277 0
Country [14] 3278 0
India
State/province [14] 3278 0
Country [15] 3279 0
Pakistan
State/province [15] 3279 0
Country [16] 3280 0
Chile
State/province [16] 3280 0
Country [17] 3281 0
Thailand
State/province [17] 3281 0

Funding & Sponsors
Funding source category [1] 264597 0
Government body
Name [1] 264597 0
National Health and Medical Research Council (NHMRC)
Address [1] 264597 0
GPO Box 1421 Canberra ACT2601
Country [1] 264597 0
Australia
Primary sponsor type
Other
Name
The George Institute for Global Health
Address
PO Box M201 Missenden Rd, Camperdown NSW2050
Country
Australia
Secondary sponsor category [1] 263736 0
None
Name [1] 263736 0
Address [1] 263736 0
Country [1] 263736 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 260593 0
Sydney South West Area Health Service Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 260593 0
Research Development Office, Royal Prince Alfred Hospital, Missenden Road, Camperdown 2050
Ethics committee country [1] 260593 0
Australia
Date submitted for ethics approval [1] 260593 0
11/04/2011
Approval date [1] 260593 0
30/06/2011
Ethics approval number [1] 260593 0
HREC\EXECOR\11-06

Summary
Brief summary
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)?
Trial website
http://www.enchanted.org.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32300 0
Prof Craig Anderson
Address 32300 0
The George Institute for Global Health PO Box M201 Missenden Rd, Camperdown NSW2050
Country 32300 0
Australia
Phone 32300 0
+61 2 9993 4500
Fax 32300 0
+61 2 9993 4502
Email 32300 0
canderson@georgeinstitute.org.au
Contact person for public queries
Name 15547 0
Prof Craig Anderson
Address 15547 0
The George Institute for Global Health
PO Box M201 Missenden Rd, Camperdown NSW2050
Country 15547 0
Australia
Phone 15547 0
+61 2 9993 4500
Fax 15547 0
+61 2 9993 4502
Email 15547 0
canderson@georgeinstitute.org.au
Contact person for scientific queries
Name 6475 0
Prof Craig Anderson
Address 6475 0
The George Institute for Global Health
PO Box M201 Missenden Rd, Camperdown NSW2050
Country 6475 0
Australia
Phone 6475 0
+61 2 9993 4500
Fax 6475 0
+61 2 9993 4502
Email 6475 0
canderson@georgeinstitute.org.au

No data has been provided for results reporting
Summary results
Not applicable