Third Enhanced Control of Hypertension and Thrombectomy Stroke Domain Within ACT-GLOBAL Adaptive Platform Trial

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Другое Conservative SBP Control
  No or minimal treatment; if there is a need to treat a patient with a very-high (\>180 mmHg) baseline SBP, then the SBP reduction is 5-10mmHg or a target is 175-180 mmHg
• Другое Moderate SBP Control
  If the patient has a very high (\>180 mmHg) or moderate high (160-180 mmHg) baseline SBP, SBP reduction is 10-20mmHg or a target of160±5 mmHg, which is higher; patients with low-high (150-160 mmHg) baseline SBP will not be treated
• Другое Intensive SBP Control
  SBP reduction by 30-50mmHg or a target of 140±5 mmHg, which is higher

Первичные конечные точки

• modified Rankin scale [Срок оценки: 90 days]

Вторичные конечные точки (9)

• Excellent functional neurological outcome [Срок оценки: 90 days]
• Independent functional neurological outcome [Срок оценки: 90 days]
• Health Related Quality of Life [Срок оценки: 90 days]
• Mortality [Срок оценки: 90 days]
• Ordinal shift of 7 levels of modified Rankin scale [Срок оценки: 90 days]
• National Institute of Health Stroke Scale (NIHSS) score [Срок оценки: 24-48 hours]
• Any intracranial haemorrhage (ICH) [Срок оценки: 2 days]
• Symptomatic intracerebral haemorrhage (sICH) [Срок оценки: 2 days]
• Serious Adverse Event (SAE) [Срок оценки: 4 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

1.Any definite contraindications to BP lowering treatment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• The George Institute for Global Health — Sydney

Канада · 1 центр

• University of Calgary — Calgary

Идентификаторы

NCT: NCT06352619 · ACT-GLOBAL_AIS_03

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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