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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,587
- 试验地点
- 1
- 主要终点
- Combined death and disability
研究概览
简要总结
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)?
The rtPA dose arm of the study addressing questions (1) and (3) concluded with a publication of the results in May 2016. The BP intensity arm of the study addressing questions (2) and (4) concluded with a publication of the results in February 2019.
详细描述
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-label, blinded endpoint (PROBE) controlled trial that involved 4587 patients (3310 for rtPA arm {recruitment completed in August 2015} and 2227 for BP arm {recruitment completed in April 2018} with 939 overlap) with acute ischaemic stroke recruited from over 100+ Clinical Centres from Australia, Asia, Europe and South America.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Low-dose rtPA (Recruitment completed in August 2015)
low-dose 0.6 mg/kg (maximum of 60 mg) i.v. rtPA
干预措施: Low-dose rtPA (Drug)
Standard-dose rtPA (Recruitment completed in August 2015)
standard-dose 0.9 mg/kg (maximum of 90 mg) i.v. rtPA
干预措施: Standard-dose rtPA (Drug)
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.
干预措施: Intensive blood pressure (BP) lowering (Other)
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.
干预措施: BP management policies (Other)
结局指标
主要结局
Combined death and disability
时间窗: 90 days
Unadjusted modified Rankin Scale \[mRS\] score 2-6
次要结局
- Admission to residential care(90 days)
- Symptomatic intracerebral hemorrhage(36 hours)
- Death or disability by the alternative, ordinal shift analysis(90 days)
- Death(at 7 and 90 days)
- Disability(90 days)
- Neurological deterioration(72 hours)
- Health-related quality of life(90 days)
- Health service use(90 days)
- Symptomatic intracerebral hemorrhage (ICH)(within 7 days)
- Any intracerebral hemorrhage (ICH)(any time during 90 days)
- Death or disability in as treated per-protocol population(90 days)
- Death or neurological deterioration(72 hours)
- Length of initial acute hospital stay(within 90 days)
- Recurrent acute myocardial infarction and ischemic stroke(within 90 days)