Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL_ENCHANTED3/MT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 2,000
- 试验地点
- 4
- 主要终点
- modified Rankin scale
研究概览
简要总结
Several clinical trials have produced variable conclusions regarding the effects of intensive blood pressure (BP) lowering in post-EVT acute ischaemic stroke (AIS) patients. Although two trials indicate harm from very intensive target-based treatment (SBP <130 mmHg), the others neutral effects in the SBP range 140-160 mmHg. The ENCHANTED3/MT domain of the ACT-GLOBAL platform trial aims to test different approaches to the treatment of elevated SBP in post-EVT AIS patients to find an optimal BP management strategy. ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to conservative (no or minimal SBP reduction by 5-10mmHg or a target of 175-180mmHg if very-high baseline SBP [≥180mmHg]), moderate (SBP reduction by 10-20mmHg or a target of 160 ± 5, whichever is higher; no control if low-high baseline SBP [150-160mmHg]), or intensive (SBP reduction by 30-50mmHg or a target of 140±5 mmHg, whichever is higher) BP management.
详细描述
ACT-GLOBAL is an international, multi-factorial, multi-arm, multi-stage, randomized, adaptive platform trial designed to simultaneously evaluate multiple treatments that may improve outcomes in stroke. One domain is ENCHANTED3/MT aiming to compare three BP lowering management strategies in post-EVT AIS patients with elevated SBP determine the best approach to improve functional outcome.
Background and Rationale - Different reperfusion status may have different BP patterns. A U-shaped correlation between post-EVT BP and outcomes may exist for patients who underwent recanalisation post-EVT. In addition, different BP lowering strategy may have different safety profiles and may potentially impact differently with regards to the risk of ICH for patients with reperfusion therapy.
The controversial overall clinical effect seen in clinical trials, including ENCHANTED2/MT, OPTIMAL BP, BP TARGET, BEST II and ENCHANTED, does not resolve the question over the optimal BP control strategy following EVT. The evidence is insufficient to make sensible recommendations over the optimal BP management in this important clinical group. Thus, the Blood Pressure Domain (ENCHANTED3/MT) aims to test different treatment approaches to the control of elevated SBP post-EVT in AIS patients to find the optimal BP management that leads to improved functional status with reduced ICH and no other harms.
ENCHANTED3/MT will randomize (1:1:1) up to 2,000 patients with SBP ≥150 mmHg post-EVT to the following three BP lowering management strategies.
Primary outcome is modified Rankin scale (mRS) at 90 days analysed with utility-weighted mRS using a Bayesian hierarchical linear model. Adaptive analyses will be conducted 3-monthly with prespecified statistical triggers for superiority, inferiority and equivalence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥18 years;
- •Use of endovascular therapy (EVT) within 24 hours of symptom onset or last known well according to local guidelines;
- •Sustained high systolic blood pressure ≥150 mmHg (2 readings <10 mins apart) within 3 hours after completion of EVT.
排除标准
- •1.Any definite contraindications to BP lowering treatment.
研究组 & 干预措施
Intensive SBP Control
干预措施: Intensive SBP Control (Other)
Conservative SBP Control
干预措施: Conservative SBP Control (Other)
Moderate SBP Control
干预措施: Moderate SBP Control (Other)
结局指标
主要结局
modified Rankin scale
时间窗: 90 days
The mRS is a 7-outcome ordered categorical scale that assesses functional neurological status after stroke. It is not intended for use as a measure of historical functional status. It is well accepted as a standard outcome around the world in the stroke community, by patients and by regulatory authorities. The seven values and the clinical summary of the individual scores are summarized in the following: 0 = No symptoms 1. = No significant disability; able to carry out all usual activities 2. = Slight disability; can look after own affairs, but unable to carry out all previous activities 3. = Moderate disability; require some help 4. = Moderately severe disability; unable to attend to own bodily needs without assistance 5. = Severe disability; bedridden and requiring constant nursing care and attention 6. = Dead
次要结局
- Independent functional neurological outcome(90 days)
- National Institute of Health Stroke Scale (NIHSS) score(24-48 hours)
- Excellent functional neurological outcome(90 days)
- Health Related Quality of Life(90 days)
- Symptomatic intracerebral haemorrhage (sICH)(2 days)
- Mortality(90 days)
- Any intracranial haemorrhage (ICH)(2 days)
- Ordinal shift of 7 levels of modified Rankin scale(90 days)
- Serious Adverse Event (SAE)(4 days)