Agonistas do Receptor do Peptídeo-1 Semelhante ao Glucagão para Trombectomia Endovascular no AVC (LEAST)
Um Ensaio Clínico Piloto Multicêntrico, Prospetivo, Randomizado, de Acesso Aberto, com Avaliação Cega dos Endpoints, a Avaliar a Semaglutida Subcutânea em Doentes com Acidente Vascular Cerebral Isquémico Agudo Devido a Oclusão de Grande Vaso da Circulação Anterior Tratados com Trombectomia Endovascular
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.
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Contato de estudo
- Nome: Jodi Miller, PhD
- Número de telefone: 905-521-2100
- E-mail: leaststudy@phri.ca
Estude backup de contato
- Nome: Amanda Taylor
- Número de telefone: 905-521-2100
- E-mail: leaststudy@phri.ca
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Semaglutide
Semaglutide |
Glucagon-like peptide-1 (GLP-1) receptor agonist
Outros nomes:
|
|
Sem intervenção: No Intervention
No Intervention |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Feasibility - Recruitment
Prazo: 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)
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Medication Adherence
Prazo: From randomization to day 90±14
|
Target >75% medication adherence |
From randomization to day 90±14
|
|
Retention Rate
Prazo: From randomization to day 90±14
|
Target >90% of study participants remaining in the trial |
From randomization to day 90±14
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Aristeidis Katsanos, MD, Population Health Research Institute
- Investigador principal: Ashkan Shoamanesh, MD, Population Health Research Institute
- Investigador principal: Mike Sharma, MD, Population Health Research Institute
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- LEAST
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
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