Agonistes des récepteurs du peptide-1 de type glucagon pour la thrombectomie endovasculaire des accidents vasculaires cérébraux (LEAST)
Un essai clinique pilote multicentrique, prospectif, randomisé, en ouvert, à évaluation en aveugle des critères de jugement, évaluant le sémaglutide sous-cutané chez les patients atteints d'accident vasculaire cérébral ischémique aigu dû à une occlusion de gros vaisseau de la circulation antérieure traités par thrombectomie endovasculaire
Endovascular thrombectomy (EVT) is a procedure that improves recovery for people who suffer from a stroke by removing blood clots from large blood vessels in the brain. However, even with this treatment, over half of the patients either pass away or are left with serious disabilities within three months. This is partly because, even in cases of a successful EVT, brain tissue damage continues to grow. Extent of brain damage is a major factor in how well a patient recovers. Studies in animals have shown that a drug called semaglutide might help protect the brain and improve recovery after a stroke. Semaglutide is currently used for the treatment of diabetes and obesity and is given as a weekly injection under the skin.
The investigators are hoping to test whether giving semaglutide to stroke patients undergoing EVT can improve their recovery. A very large study at many hospitals is needed to answer this question. The investigators are starting with a smaller study to gain information on whether it is possible to perform a larger definitive one, and if so, how best to plan for it. In this first step we will study 100 patients with stroke who are scheduled for EVT in approximately 10 stroke centers across Canada. These patients will be randomly divided (like flipping a coin) into two groups: one will receive weekly semaglutide injections for 12 weeks, while the other will not receive the drug. The investigators will track how many patients agree to participate, how many stay in the study, and how well they follow the treatment plan. The investigators will also monitor the patients' recovery, overall health, and any side effects from the treatment. These results will provide important information to plan our larger study with the goal of reducing death rates and long-term disability in stroke patients undergoing EVT.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Background/Importance:
Endovascular thrombectomy (EVT) has substantially improved functional outcomes and decreased mortality in acute ischemic stroke patients with large vessel occlusions (LVOs). However, more than half of the patients die or have significant disability at 90 days after EVT. Studies suggest considerable infarct growth despite successful EVT and infarct volume predicts survival and functional outcome after EVT. There is an unmet need for interventions to reduce infarct growth and improve the functional outcomes of patients with an acute LVO who undergo EVT. Glucagon-Like Peptide-1 receptor agonists (GLP-1 RAs) have been suggested to decrease infarct growth and improve motor and sensory impairments in both diabetic and non-diabetic animal models of stroke. GLP-1 RAs also consistently decreased the risk of major adverse cardiovascular events (MACE), with the most profound effect in stroke prevention, in large-scale randomized clinical trials (RCTs) of patients with and without history of diabetes.
Research Aims:
The overall goal of this study is to test whether semaglutide can improve the functional outcomes of adults with acute ischemic stroke attributed to an intracranial LVO who are planned for treatment with EVT. We are performing a pilot trial to obtain the factual feasibility prerequisites essential for the planning, design, funding and execution of a subsequent main phase trial.
Methods:
Glucagon-like peptide-1 receptor agonists for Endovascular Stroke Thrombectomy (LEAST) is a multicentre, prospective, randomized, open label, blinded endpoint (PROBE) pilot clinical trial. LEAST will recruit a total of 100 adult patients scheduled to receive EVT at approximately 10 high-volume stroke research centres in Canada over 1.5 to 2 years. Participants fulfilling the inclusion and exclusion criteria will be randomly assigned up to 6 hours from the end of the EVT procedure, defined as the time of the last angiographic run, to either receive semaglutide (0.25 mg subcutaneous [SC] weekly for 4 weeks followed by 0.5 mg SC weekly for another 8 weeks) or to no semaglutide treatment.
Outcomes:
The primary feasibility endpoint is recruitment rate.
Secondary feasibility endpoints include retention rates and medication adherence.
Exploratory outcomes include:
Proportion of participants with functional independence (mRS scores 2 or less) at 90±14 days; Absolute difference in the NIHSS scores between randomization and 36±12 hours; Functional outcome at day 7±2, assessed with the ordinal mRS scores; Proportion of participants with functional independence (mRS scores 2 or less) at day 7±2; Functional outcome at day 30±7, assessed with the ordinal mRS scores; Proportion of participants with functional independence (mRS scores 2 or less) at day 30±7; Functional outcome at 90±14 days, assessed with the ordinal mRS scores; Quality of life at 90±14 days, assessed with the EQ-5D-5L scale; Recurrent stroke (ischemic, hemorrhagic or uncertain) by 90±14 days; Occurrence of MACE (any stroke, myocardial infarction cardiovascular death) by 90±14 days.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
Contacts et emplacements
Coordonnées de l'étude
- Nom: Jodi Miller, PhD
- Numéro de téléphone: 905-521-2100
- E-mail: leaststudy@phri.ca
Sauvegarde des contacts de l'étude
- Nom: Amanda Taylor
- Numéro de téléphone: 905-521-2100
- E-mail: leaststudy@phri.ca
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Age 18 years or above on the date of randomization.
- EVT for an LVO in the anterior circulation, defined as the intracranial segment of the internal carotid artery (ICA) and/or the M1 or proximal M2 segment of the middle cerebral artery (MCA).
- National Institutes of Health Stroke Scale (NIHSS) ≥ 6 points at the time of randomization.
- Pre-stroke modified Rankin Scale (mRS) 0 or 1.
- Ability to randomize within 6 hours from the end of EVT.
- Capable of giving signed informed consent either independently, or by a legally authorized representative (LAR).
Exclusion Criteria:
- Pregnancy or breast-feeding.
- Renal insufficiency (creatinine clearance < 30mL/min).
- Cirrhosis or severe hepatic dysfunction, characterized by jaundice, encephalopathy or coagulopathy.
- History of pancreatitis in the year prior to randomization or evidence of acute pancreatitis on randomization.
- Active sepsis on randomization.
- Cancer, regionally advanced or metastatic, or for which treatment had been administered within 6 months from randomization, or hematological cancer that is not in complete remission.
- Any terminal medical condition with life expectancy of less than 3 months.
- Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).
- Body mass index (BMI) less than 19.
- Known hypersensitivity to GLP-1 RAs.
- Active treatment with an GLP-1RA prior to randomization.
- Refusal or inability to administer subcutaneous (SC) injections by the patient or a caregiver.
- Close affiliation with the investigational site.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Seul
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Semaglutide
Semaglutide |
Glucagon-like peptide-1 (GLP-1) receptor agonist
Autres noms:
|
|
Aucune intervention: No Intervention
No Intervention |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Feasibility - Recruitment
Délai: From site activation until the end of recruitment (approximately 24 months)
|
Recruitment of approximately 7 patients per site per year at approximately 10 Canadian stroke centres |
From site activation until the end of recruitment (approximately 24 months)
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Medication Adherence
Délai: From randomization to day 90±14
|
Target >75% medication adherence |
From randomization to day 90±14
|
|
Retention Rate
Délai: From randomization to day 90±14
|
Target >90% of study participants remaining in the trial |
From randomization to day 90±14
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Aristeidis Katsanos, MD, Population Health Research Institute
- Chercheur principal: Ashkan Shoamanesh, MD, Population Health Research Institute
- Chercheur principal: Mike Sharma, MD, Population Health Research Institute
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- LEAST
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .