A Multi-faCtorial, mulTi-arm, Multi-staGe, Randomised, gLOBal Adaptive pLatform Trial for Stroke (ACT-GLOBAL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 20,000
- 试验地点
- 2
- 主要终点
- modified Rankin scale (mRS) scores
研究概览
简要总结
Stroke is causing 6.6 million deaths and is a major cause of disability worldwide in 2019. There remains an urgent need for interventions that improve outcomes which can be implemented with wide applicability for stroke. ACT-GLOBAL is a multi-factorial, multi-arm, multi-stage, randomised, global adaptive platform trial for stroke, aiming to identify the treatment/s associated with the highest chance of improving outcome in stroke patients. In ACT-GLOBAL multiple questions will be evaluated simultaneously and sequentially as data accrues and can evaluate interactions between different treatment options.
详细描述
Stroke is the second leading cause of death, worldwide. It is also the second largest cause of disability-adjusted-life-years (DALYs) lost after ischaemic heart disease in developing countries, and third largest contributor to DALYs in developed countries (after ischaemic heart disease, low back and neck pain). In 2019, the absolute numbers of new strokes (12.2 million), stroke-related deaths (6.6 million), and people living with stroke (101.5 million) had increased globally from 1990 (70%, 43%, and 85% increases, respectively).
Steady progress has been made in establishing specific management strategies for patients affected by, or at high-risk of, stroke. Unfortunately, only a few acute treatments have been proven to be beneficial: thrombolysis, endovascular thrombectomy, hemicraniectomy, stroke unit care, and aspirin. There is a continued need for interventions that improve outcomes which can be implemented with wide applicability for stroke.
ACT-GLOBAL is an investigator-initiated, multi-factorial, multi-arm, multi-stage, randomised, global adaptive platform trial for stroke, aiming to find the treatment/s associated with the highest chance of improving outcome after stroke. In ACT-GLOBAL multiple questions will be evaluated simultaneously and sequentially as data accrues and can evaluate interactions between different treatment options.
Frequent adaptive analyses are conducted to assess whether a given intervention is superior, inferior, or equivalent either within a domain or for specific populations within the domain. Where it is anticipated that interactions between interventions in different domains may be likely, the statistical models will allow evaluation of such interactions. Each intervention within a domain with prospectively defined and mutually exclusive strata (sub-groups) of participants will be evaluated within the strata, while information from one stratum may be used (via 'borrowing') to contribute to the analysis of the effect of that intervention in other strata. Specific interventions or subgroups within overall populations may be dropped or cease to enrol, based on pre-specified rules.
The adaptive design allows new interventions or domains or both to be introduced. A Response Adaptive Randomisation algorithm may be used to preferentially randomize participants to interventions that appear to be performing better in domains where applicable.
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
- •Platform Inclusion Criteria:
- •Age ≥18 years
- •Clinical diagnosis of stroke
排除标准
- •There are no platform level exclusion criteria
- •Each state and domain will specify additional inclusion and exclusion criteria in the respective Domain-Specific Registration. Patients who fulfill the overall platform criteria will be assessed for enrollment into each active domain.
研究组 & 干预措施
IV thrombolysis domain
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to optimize the use of intravenous Tenecteplase in participants with Acute Ischemic Stroke.
干预措施: Standard-dose intravenous tenecteplase (Drug)
INTERACT5 Domain
This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke.
The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.
干预措施: Both deferoxamine mesylate and colchicine (Drug)
INTERACT5 Domain
This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke.
The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.
干预措施: Colchicine only (Drug)
IV thrombolysis domain
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to optimize the use of intravenous Tenecteplase in participants with Acute Ischemic Stroke.
干预措施: Low-dose intravenous tenecteplase (Drug)
IV thrombolysis domain
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to optimize the use of intravenous Tenecteplase in participants with Acute Ischemic Stroke.
干预措施: No intravenous tenecteplase (Other)
Blood Pressure domain
Third Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED3/MT) as a domain of ACT-GLOBAL to compare three BP lowering management strategies, that of conservative, moderate and intensive BP lowering in patients with Acute Ischaemic Stroke admitted to participating hospitals who has an elevated SBP after reperfusion therapy via Endovascular Thrombectomy, and reliably determine, which approach leads to improved functional outcome.
Locally available and approved i.v. BP lowering agents can be used in this domain.
干预措施: Conservative Blood Pressure Control (Other)
Blood Pressure domain
Third Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED3/MT) as a domain of ACT-GLOBAL to compare three BP lowering management strategies, that of conservative, moderate and intensive BP lowering in patients with Acute Ischaemic Stroke admitted to participating hospitals who has an elevated SBP after reperfusion therapy via Endovascular Thrombectomy, and reliably determine, which approach leads to improved functional outcome.
Locally available and approved i.v. BP lowering agents can be used in this domain.
干预措施: Moderate Blood Pressure Control (Other)
Blood Pressure domain
Third Enhanced Control of Hypertension and Thrombectomy Stroke Study (ENCHANTED3/MT) as a domain of ACT-GLOBAL to compare three BP lowering management strategies, that of conservative, moderate and intensive BP lowering in patients with Acute Ischaemic Stroke admitted to participating hospitals who has an elevated SBP after reperfusion therapy via Endovascular Thrombectomy, and reliably determine, which approach leads to improved functional outcome.
Locally available and approved i.v. BP lowering agents can be used in this domain.
干预措施: Intensive Blood Pressure Control (Other)
ACT-42 domain
This domain has a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive design and aim to determine the efficacy and safety of NoNO-42 in participants with Acute Ischaemic Stroke selected for thrombolysis with or without Endovascular Thrombectomy.
干预措施: Placebo (Other)
INTERACT5 Domain
This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke.
The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.
干预措施: No deferoxamine mesylate and no colchicine (Other)
ACT-42 domain
This domain has a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive design and aim to determine the efficacy and safety of NoNO-42 in participants with Acute Ischaemic Stroke selected for thrombolysis with or without Endovascular Thrombectomy.
干预措施: NoNO-42 (Drug)
INTERACT5 Domain
This is a domain within the Intracerebral Haemorrhage State of the ACT-GLOBAL adaptive platform trial for stroke.
The objective of this domain is to determine the efficacy of intravenous deferoxamine and low-dose oral colchicine, both individually and in combination, compared to standard of care alone, on improving functional outcome in patients with acute spontaneous supratentorial ICH.
干预措施: Deferoxamine mesylate only (Drug)
结局指标
主要结局
modified Rankin scale (mRS) scores
时间窗: Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration)
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
- Excellent functional neurological outcome(Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration))
- Independent functional neurological outcome(Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration))
- Health Related Quality of Life(Platform level time frame: 90 days in Ischaemic Stroke State; 6 months in Intracerebral Haemorrhage State; Domain specific time frame may differ (details will be included in domain-specific registration))