APEX-STROKE Adaptive Platform Trial for Stroke
Integrated Adaptive Platform for EXcellent Clinical Trials in STROKE (APEX-STROKE): A Multi-factorial, Multi-arm, Multi-stage, Randomized, Adaptive Platform Trial
Studienübersicht
Status
Bedingungen
Detaillierte Beschreibung
Stroke is a leading cause of death and disability worldwide. According to the Global Burden of Disease (GBD) 2021 Study, there were 11.9 million incident strokes, 93.8 million stroke survivors, and 7.3 million stroke-related deaths globally in 2021, making stroke the third leading cause of death after ischemic heart disease and COVID-19. Global disability-adjusted life years (DALYs) attributable to stroke rose from 121.4 million in 1990 to 160.5 million in 2021, with more than three-quarters of this burden borne by low- and middle-income countries.
Despite this burden, only a small number of acute stroke treatments have been proven effective, including thrombolysis, endovascular thrombectomy, hemicraniectomy, stroke unit care, and aspirin. Conventional randomized controlled trials test a single intervention under fixed assumptions and are often costly, resource-intensive, and slow. Adaptive platform trials (APTs) allow multiple interventions to be evaluated simultaneously within shared infrastructure, with interventions added or removed over time, offering greater efficiency than conventional designs.
APEX-STROKE is an investigator-initiated, multi-factorial, multi-arm, multi-stage, randomized, adaptive platform trial designed to identify the treatment(s) associated with the highest chance of improving patient outcomes in stroke. The platform is structured hierarchically: a Master Protocol establishes trial-wide processes, governance, and general statistical principles common to all domains; each disease State is further defined in a State Subprotocol; and each treatment Domain within a State is defined in a Domain-Specific Appendix (DSA). Full eligibility, interventions, and outcome measures for each active domain are specified in the respective DSA.
Depending on the domain, the statistical framework may be frequentist, Bayesian, or another appropriate approach, as specified in the relevant Statistical Analysis Appendix. Where pre-specified, adaptive analyses assess whether an intervention is superior, inferior, equivalent, or futile within a domain or in specific populations, and information may be "borrowed" across strata where justified. Where interactions between interventions in different domains are considered plausible, the statistical models may evaluate such interactions. Response Adaptive Randomization (RAR) may be used, where pre-specified, to adjust allocation probabilities as data accrue. Specific interventions, subgroups, or domains may be stopped, modified, or closed to enrollment based on pre-specified decision rules reviewed by an independent Data Safety Monitoring Board.
Unlike trial designs that prohibit co-enrollment, the platform design permits assessment of synergy, competitive interference, and safety of combined treatment strategies across domains, subject to pre-specified eligibility, randomization, and analysis rules. The intention-to-treat principle will be used for all primary and adaptive analyses unless otherwise specified at domain level.
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 3
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
Platform Inclusion Criteria:
- Age ≥18 years
- Clinical diagnosis of stroke
Platform Exclusion Criteria
- 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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Single
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
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Experimental: Angong Niuhuang Pill domain
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to determine the efficacy and safety of Angong Niuhuang Pills in participants with acute ischemic stroke whose symptom onset is within 6 hours.
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Participants randomized into the intervention arm receive Angong Niuhuang Pills (ANP, 3 g/pill).
The initial dose is given orally for awake patients or via route-specific methods for unconscious patients: if randomized in the ambulance, a 15 mL suspension is administered sublingually (2-2.5 mL every 10 min) with the remainder via nasogastric tube (NGT) post-admission; if randomized in the ED, the suspension is given directly via NGT when indicated.
Maintenance dosing follows: one pill twice daily in week 1 and once daily in week 2 (14 days total).
Suspensions are prepared by grinding one shelled pill with 15 mL room-temperature saline and must be used within 1 hour.
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Experimental: EAGLE domian
This domain has a prospective, randomized, controlled, open-label, parallel group with blinded endpoint assessment (PROBE) design to determine the efficacy of surgical bundles in participants with acute ischemic stroke whose symptom onset is within 8 hours.
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Early minimally invasive surgery (MIS) is initiated within 8 hours after symptom onset; intensive systolic blood pressure control targeting 130-140 mmHg is achieved within 1 hour post-randomisation and sustained for 7 consecutive days; tranexamic acid (TXA) haemostatic therapy: 1g loading dose infused over 10 minutes, followed by 1g maintenance dose given via 8-hour intravenous infusion, started within 30 minutes after random allocation • Standard guideline routine care only: All patient management is determined per local institutional ICH guidelines; elective MIS is prohibited within 12 hours of symptom onset except for emergency life-saving surgery; no mandatory intensive blood pressure management or routine TXA administration is permitted |
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Experimental: CHAIN-2 domain
This study employs a multicenter, prospective, randomized, double-blind clinical trial design to evaluate the safety and efficacy of Yiqi Huayu Jiedu Mixture (composed of Red Ginseng, Notoginseng, and Raw Rhubarb) in participants with acute supratentorial hypertensive intracerebral hemorrhage (HICH) who are not undergoing surgical intervention, targeting the core syndrome pattern of "deficiency-stasis-toxin" in the acute phase.
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Yiqi Huayu Jiedu Mixture is a standardized traditional Chinese medicine oral liquid formulated based on the "benefiting qi, resolving stasis, and detoxifying" therapeutic principle for acute supratentorial hypertensive intracerebral hemorrhage (HICH).
Each 100 mL bottle contains Red Ginseng (30 g), Notoginseng (30 g), and Raw Rhubarb (5 g), prepared under GMP standards at Guangdong Provincial Hospital of Chinese Medicine.
Administration begins within 48 hours of symptom onset for a total duration of 28 days.
For patients able to take oral medication: 33 mL three times daily, taken at least 30 minutes after meals (total 100 mL/day).
For patients with dysphagia, insufficient oral intake, unconsciousness, or critical illness: 25 mL via nasogastric tube four times daily (every 6 hours).
The formulation aims to restore vital qi, promote blood circulation without damaging healthy qi, and eliminate pathological toxins to facilitate neurological recovery in non-surgical HICH patients.
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Modified Rankin Scale (mRS) score
Zeitfenster: Platform level time frame:180 days in Intracerebral Hemorrhage State; 90 days for Ischemic Stroke State. Specific time frame will be included in domain-specific registration.
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The modified Rankin Scale (mRS) is a 7-level ordered categorical scale (range: 0-6) assessing levels of disability and death after stroke, where higher scores indicate worse outcome (0 = no symptoms; 6 = death).
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.
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Platform level time frame:180 days in Intracerebral Hemorrhage State; 90 days for Ischemic Stroke State. Specific time frame will be included in domain-specific registration.
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Mortality
Zeitfenster: 180 days
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All-cause mortality will be reported as the number and proportion of participants who died from any cause by 180 days after randomization.
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180 days
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NIHSS score
Zeitfenster: 24 hours and Day 7
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National Institutes of Health Stroke Scale (NIHSS) score.
The NIHSS is a 15-item neurological examination scale used to quantify stroke severity, ranging from 0 (no stroke symptoms) to 42 (severe stroke), with higher scores indicating worse outcome.
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24 hours and Day 7
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Death or major disability
Zeitfenster: 180 days
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Participants achieved death or major disability if they scored 3-6 on the modified Rankin Scale (mRS), a scale ranging from 0 (no symptoms) to 6 (death), with higher scores indicating worse outcome.
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180 days
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Health-Related Quality of Life
Zeitfenster: Platform level time frame: 180 days in Intracerebral Hemorrhage State; 90 days in Ischemic Stroke State. Domain specific time frame may differ (details will be included in domain-specific registration)
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Health Related Quality of Life based on EuroQol 5 Dimension 5 Level (EQ-5D-5L).The EQ-5D-5L is a generic instrument for describing and valuing health.
It is based on a descriptive system that defines health in terms of five dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression.
Each dimension has five response categories corresponding to: no problems, slight, moderate, severe and extreme problems.
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Platform level time frame: 180 days in Intracerebral Hemorrhage State; 90 days in Ischemic Stroke State. Domain specific time frame may differ (details will be included in domain-specific registration)
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Mitarbeiter und Ermittler
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
Andere Studien-ID-Nummern
- APEX-STROKE
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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