Enhanced control of hypertension and thrombolysis stroke study

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12611000236998
• Date of registration: 03/03/2011
• Prospective Registration: Yes
• Primary sponsor: The George Institute for Global Health
• 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
• Date of first enrolment: 03/03/2012
• Target sample size: 4500
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12611000236998.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Randomised controlled trial; Masking: Open (masking not used);Assignment: Parallel;Type of endpoint: Safety/efficacy;
• Phase: Phase 3 / Phase 4

Countries of recruitment

Australia, Austria, Chile, China, France, Hong Kong, India, Italy, Korea, Republic Of, New Zealand, Pakistan, Portugal, Singapore, Spain, Swaziland, Thailand, United Kingdom, Viet Nam

Contacts

• Name: Prof Craig Anderson

• Name: Prof Craig Anderson

Key inclusion & exclusion criteria

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
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.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Stroke - Ischaemic

Ischaemic stroke;Hypertension;
Ischaemic stroke
Hypertension

Cardiovascular - Hypertension

Intervention(s)

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.

Primary Outcome(s)

RtPA dose arm: death and any disability (modified Rankin Scale [mRS] score 2-6) [90 days]

Blood Pressure intensity arm: mRS ordinal shift[90 days]

Secondary Outcome(s)

death or disability by shift analysis of scores on modified Rankin Scale (mRS)[90 days]

death[90 days]

disability (modified Rankin Scale [mRS] score 2-5)[90 days]

neurological deterioration (deterioration in NIH Stroke Scale [NIHSS] score and/or Glasgow Coma Scale [GCS] score)[72 hours]

symptomatic intracerebral haemorrhage (confirmed by CT [or necropsy] with deterioration in NIH Stroke Scale [NIHSS] score)[36 hours]

any intracerebral haemorrhage in CT scans[7 days]

health-related quality of life by the EuroQoL[90 days]

admission to residential care by in-person or telephone follow-up[90 days]

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[90 days]

Secondary ID(s)

NIl

Source(s) of Monetary Support

National Health and Medical Research Council (NHMRC)

Ethics review

Status: Approved
Approval date:
Contact:

Sydney South West Area Health Service Ethics Review Committee (RPAH Zone)

Results

• Results available: Yes
• Date Posted: 19/09/2019
• Date Completed: 22/08/2018