None listed
Conditions
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)?
Interventions
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
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.
Sponsors
The George Institute for Global Health
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
Outcome results
None listed