Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)

Condition(s) targeted: Ischemic Stroke; High Blood Pressure

Intervention: Low-dose rtPA (Drug); Standard-dose rtPA (Drug); Intensive blood pressure (BP) lowering (Other); BP management policies (Other)

Phase: Phase 3

Status: Recruiting

Sponsored by: The George Institute

Official(s) and/or principal investigator(s):
Craig S Anderson, MD, Principal Investigator, Affiliation: The George Institute for Global Health

Overall contact:
Hisatomi Arima, MD, Phone: +61 2 9993 4500, Email: harima@georgeinstitute.org.au

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)?

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Combined death and any disability

Secondary outcome:

Symptomatic intracerebral hemorrhage

Intracerebral hemorrhage of any type in CT scans

Death or disability by the alternative, but less widely used, shift analysis

Death

Disability

Neurological deterioration

Health-related quality of life

Admission to residential care

Health service use

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

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

Royal Prince Alfred Hospital, Sydney, New South Wales 2050, Australia; Recruiting
Craig S Anderson, MD, Phone: +61 2 933 4500, Email: canderson@georgeinstitute.org.au

Starting date: March 2012
Last updated: November 15, 2012