NoNO-42 Trial in Acute Ischemic Stroke Patients Selected for Thrombolysis With or Without Endovascular Thrombectomy

Официальное название

A Multicentre, Prospective, Randomized, Open Label, Blinded-Endpoint, Placebo-controlled, Single-dose Trial to Determine the Efficacy and Safety of NoNO-42 in Participants With Acute Ischemic Stroke Selected for Thrombolysis With or Without Endovascular Thrombectomy (ACT-42 Trial)

Обзор

ACT-42 is a domain of the ACT-GLOBAL platform (NCT06352632). This trial is a Phase 2b, multicenter, prospective, randomized, open label, blinded-endpoint (PROBE) controlled single-dose adaptive trial. A total of up to 600 male and female participants aged ≥ 18 to ≤ 90 years harboring an acute ischemic stroke who are eligible for an intravenous thrombolytic with or without endovascular thrombectomy therapy will be enrolled within 4.5 hours of stroke onset/last known well.

Подробное описание

Because AIS is a medical emergency, the trial is designed to enable the administration of standard-of-care treatments in order to save the life of the person concerned, restore good health and alleviate suffering.

A total of up to 600 male and female participants aged ≥ 18 to ≤ 90 years harboring an acute ischemic stroke who are eligible for an intravenous thrombolytic with or without endovascular thrombectomy therapy will be enrolled within 4.5 hours of stroke onset/last known well. Randomization will be 1:1 drug/placebo. Randomization will be stratified by large vessel occlusion (LVO) (yes/no) and a minimization algorithm to minimize the contribution of imbalances in baseline factors (age, sex, baseline NIHSS score). The design is adaptive with prospective rules for adaptive enrichment, in which enrollment may be restricted to participants without an LVO. LVO is defined as an occlusion of the intracranial ICA, M1 or proximal M2.

Randomized participants will receive/received an intravenous thrombolytic and be allocated to:

* the investigational group, a single, 2.6 mg/kg (up to a maximum of 300 mg) 20-minute intravenous dose of NoNO-42, with a target start time of less than 10 minutes from randomization or * the control group, no trial specific intervention.

Day 90: All participants will be followed for 90 days (or until death if prior to 90 days) for efficacy and 30 days for safety. The end of the trial is defined as the date that all participants have completed their Day 90 contact.

1-Year follow Up: participants who completed the trial to Day 90 may be followed at 1 year for long-term efficacy.

One database lock and corresponding report for the trial to Day 90 and a separate database lock and analysis for the 1-year follow up are planned.

Вмешательства

• Препарат NoNO-42
  a single dose sterile 20 ml vial containing lyophilized powder for reconstitution containing 300 mg of NoNO-42 active ingredient.

Первичные конечные точки

• Reducing global disability in participants with acute ischemic stroke (AIS) [Срок оценки: 90 days from intervention]

Вторичные конечные точки (5)

• Improving excellent functional outcome [Срок оценки: 90 days from intervention]
• Reducing worsening of stroke [Срок оценки: 90 days from intervention]
• Improving functional independence [Срок оценки: 90 days from intervention]
• Reducing mortality rate [Срок оценки: 90 days from intervention]
• Improving health-related quality of life [Срок оценки: 90 days from intervention]

Критерии участия

Критерии включения

• Confirmed or suspected acute ischemic stroke (AIS) selected for intravenous thrombolysis.
• Onset (last-known-well) time to randomization time within 4.5 hours.
• Ages ≥ 18 to ≤ 90 years.
• Disabling stroke defined as a baseline National Institutes of Health Stroke Score (NIHSS) >5.
• Confirmed or suspected symptomatic anterior circulation intracranial occlusion. Tandem extracranial carotid and intracranial occlusions are permitted.
• Pre-stroke independent functional status in activities of daily living as judged by the enrolling physician. Patient must be living without requiring nursing care.
• Consent process completed as per national laws and regulation and the applicable ethics committee requirements.

Критерии исключения

• Large extent early ischemic changes/infarct in the ischemic territory on qualifying imaging.
• Any intracranial hemorrhage on qualifying imaging.
• Unlikely to initiate study drug administration before arterial puncture in those selected for EVT.
• Known/suspected pregnancy and/or lactation.
• Systolic blood pressure < 90 mmHg
• Known prior receipt of NoNO-42 for any reason, including prior enrolment in this trial.

8\) Severe comorbid illness with life expectancy less than 90 days, or likely to prevent completing 90-day follow-up.

9\) Long term care facility resident or prisoner 10) Participation in another clinical trial outside of the ACT-GLOBAL platform investigating a drug or medical device or a neuro-interventional or surgical procedure that is not considered as standard care in the 30 days preceding trial enrolment.

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

Открытое

Основная цель

Лечение

Центры проведения

Канада · 9 центров

• University of Calgary - Foothills Medical Centre — Calgary
• University of Alberta Hospital — Edmonton
• Vancouver General Hospital — Vancouver
• University of Manitoba — Winnipeg
• Hamilton General Hospital — Hamilton
• Ottawa Hospital Research Institute — Ottawa
• Sunnybrook Health Sciences Centre — Toronto
• Unity Health Toronto, St. Michael's Hospital — Toronto
• … и ещё 1 центр

Идентификаторы

NCT: NCT06403267 · NoNO42-02 (ACT-42)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗