QUantum Genomics Incremental Dosing in Heart Failure - QUID-HF (QUID-HF)
11 de outubro de 2018 atualizado por: Quantum Genomics SA
A Randomized, Double-blind, Multi-centre Study to Assess Safety and Efficacy of Incremental Doses of QGC001 in Patients With NYHA Class II/III Chronic Heart Failure (HF) With Left Ventricular Systolic Dysfunction Versus Placebo.
Heart Failure (HF) a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.
A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.
QCG001 is a prodrug of EC33, a aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.
This study investigates the safety and efficacy of QGC001 in HF patients.
Visão geral do estudo
Status
Rescindido
Condições
Intervenção / Tratamento
Descrição detalhada
Despite advances in care, prognosis remains poor once overt Heart Failure (HF) has developed. HF is a common clinical condition characterized by either by a heart that does not pump sufficiently or becomes stiff and it is associates with higher incidences of patient illness and death in both case. A variety of mechanisms contribute to progressive cardiac remodeling and dysfunction.
A new therapeutic approaches by preventing activation of the brain neuromodulatory pathway, may lead to improve HF.
QCG001 is a prodrug of EC33, a specific and selective of the aminopeptidase A (APA) inhibitor. QCG001 has been shown to be an antihypertensive agent in animal models.
This study investigates the safety and efficacy of QGC001 up-titrated form 50mg twice daily to a maximum of 500 mg twice daily, on patients with worsening chronic HF during 28 days and 7 days after discontinuation (day 35).
6 European countries are involved in this study (France, Netherlands, Germany, Norway, Poland and United Kingdom) including 20 investigational hospitals. Patients would be followed during 35 days and inclusion period lasts until December 2017.
Tipo de estudo
Intervencional
Inscrição (Real)
23
Estágio
- Fase 2
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Berlin, Alemanha
- Charity Universitatsmedizin Berlin
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Hannover, Alemanha, D-30625
- Medizinische Hochschule Hannover
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Homburg, Alemanha, 66421
- Klinik für Innere Medizin III
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Bron, França, 69677
- Hopital Louis Pradel
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Montpellier, França, 34295
- Hopital Arnaud de Villeneuve
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Nancy, França, 54500
- CHRU NANCY
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Nantes, França, 44093
- Hôpital Laennec
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Paris, França, 75013
- Hôpital Pitie Salpétrière
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Paris, França, 75015
- Georges Pompidou European Hospital
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Rouen, França, 76031
- Hôpital Charles Nicolle
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Strasbourg, França, 67000
- Hopitaux Universitaires de Strasbourg
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Toulouse, França, 31000
- Clinique Pasteur
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Groningen, Holanda, 9713GZ
- University Medical Center Groningen
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Maastricht, Holanda, PO 5800
- Maastricht University Medical Centre
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Budapest, Hungria, 1134
- Magyar Honvedseg Egeszsegugyi Kozpont
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Budapest, Hungria, 1122
- Heart and Vascular Center of Semmelweis University
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Stavanger, Noruega, 4011
- Stavanger University Hospital
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Wroclaw, Polônia, 50981
- Clinical Military Hospital
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Łódź, Polônia, 94048
- NZOZ All-Med Centrum Medyczne
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Dundee, Reino Unido, DD1 9SY
- Ninewells Hospital
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England
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Birmingham, England, Reino Unido, B18 7QH
- University of Birmingham Institute of Cardiovascular Sciences City Hospital,
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Frýdek-Místek, Tcheca, 73801
- Hospital of Fridek-Mistek P.O.
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Praha, Tcheca, 12808
- General University Hospital
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos e mais velhos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Inclusion Criteria:
- A signed and dated informed consent form prior to any study procedure
- Adult male subjects and female subjects without childbearing potential.
- Clinical diagnosis of CHF with history of NYHA class II-III for at least 3 months before randomisation.
- Documented left ventricular ejection fraction (LVEF) < 40% measured by any modality within the previous 12 months in the subject's medical history.
- Subjects must also have at least one local measurement of BNP level ≥ 300 pg/mL or NT-proBNP level ≥ 1200 pg/mL (preferred assay, local laboratory) at the screening visit (maximum 7 days before randomisation).
- eGFR > 30 mL/min/1.73 m2 (MDRD) at screening.
- Serum potassium < 5.0 mmol/L at screening.
- Systolic blood pressure < 110 mmHg (average of 3 consecutive measurements) at screening.
- Prescribed to optimal pharmacologic therapy per "ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2016", or based on the updated current clinical practice, unless contra-indicated or not-tolerated, and on a stable dose for at least 30 days prior to enrolment (the dosage of the drugs cannot be increased or decreased respectively by more than double or half of initial dosage).
- Taking oral loop diuretics at doses < 250 mg furosemide daily (or equivalent).
Exclusion Criteria:
- BMI > 45 kg.m-2.
- Patients who require the use of HF IV therapy or oral furosemide > 250 mg (or equivalent) at any time during the 48 hours immediately before randomisation.
- Patients with unstable angina, myocardial infarction, PTCA, coronary artery bypass graft, cerebral vascular accident, or transient ischemic attack within previous 3 months (90 days) before enrolment.
- Patients whose primary cause of heart failure is mitral or aortic valve disease or congenital heart disease or hypertrophic obstructive cardiomyopathy or infiltrative cardiomyopathy (e.g. amyloidosis, sarcoidosis) or myocarditis.
- Patients with "new" permanent atrial fibrillation (AF), discovered within 3 months prior to randomization.
- Heart rate > 110 beats/min at screening.
- Patients scheduled for Pacemaker (including ICD, CRT), Angioplasty, CABG or LVAD within the next 3 months.
- Patients with severe documented chronic obstructive lung disease (COPD), defined as chronic need for oxygen therapy
- eGFR < 30 mL/min/1.73 m2 (MDRD) at screening.
- Decrease in eGFR greater than 20% within 3 weeks prior to the screening visit.
- Serum potassium > 5.0 mmol/L at screening.
- Systolic blood pressure < 110 mmHg or with signs or symptoms of hypotension.
- Symptomatic hypotension or orthostatic hypotension defined by a decrease of systolic blood pressure of more than 30 mm Hg in the standing vs. sitting position at screening and at the basal SBP of the D0 (before having taken the study medication).
- A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstrated of a QTc interval > 450 ms) AND QRS < 100 ms. In case of QRS enlargement > 100 ms (i-e bundle branch block, pacemakers) QT does not accurately reflect repolarization and may not be calculated.
- A history of additional risk factors for Torsade de Pointes (TdP) (e.g. hypokalemia, family history of long QT Syndrome).
- The use of concomitant medications that prolong the QT/QTc interval.
- Insulin-requiring diabetic patients (including type 1 Diabetes).
- History of angioneurotic edema.
- Severe liver failure at screening defined by a value of ALAT and/or ASAT≥ 5 from the normal value.
- Patients involved in any interventional clinical study, patients enrolled in Registries and/or in non-interventional studies may participate.
- Patients who take an investigational or non-approved treatment.
- Women of childbearing potential.
- Patients with a prior cardiac transplant or patients currently on the list for cardiac transplantation.
- Patient with hypersensitivity to the active substance or to one of the other components of the trial preparation.
- Patients in whom an allergy requiring chronic treatment is known or exists.
- Patients with a history of previous illnesses of neurological or psychiatric nature that affect the Central Nervous System.
- Patients with a life expectancy of less than 12 months per physician judgment.
- Frail patient who, in the opinion of the investigator will not be able to follow the protocol.
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: QGC001
QGC001 from 50mg to 500mg capsule twice daily, for 28 days, oral use
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Comparador de Placebo: Placebo
Placebo, capsule twice daily, for 28 days, oral use
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Lactose capsule manufactured to mimic QGC001 50 mg and 250 mg
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Relative decrease in NT-proBNP
Prazo: 28 days
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Percentage of subjects with a relative decrease in NT-proBNP of more than 30% from Baseline to day 28.
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28 days
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Blood pressure change
Prazo: 28 days
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Blood pressure changes at each visit (D7, D14, D21, D28), compared to the Baseline measure
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28 days
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Blood biochemistry
Prazo: 35 days
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blood biochemistry at D7, D14, D21, D28 and D35.
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35 days
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Urinary biochemistry
Prazo: 35 days
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electrolytes, urinary osmolarity at D7, D14, D21, D28 and D35.
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35 days
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Change of NT-proBNP
Prazo: 35 days
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Changes in central lab values of NT-proBNP at D7, D14, D21, D28 and D35.
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35 days
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Change of BNP
Prazo: 35 days
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Changes in central lab values of BNP at D7, D14, D21, D28 and D35.
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35 days
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Change of selected biomarker levels
Prazo: 28 days
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Changes in central lab values from baseline in selected biomarker levels (biomarkers involved in the pathophysiology of the disease, which will be decided later) at Day 7, Day 14, Day 21, Day 28
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28 days
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Quality of life Minnesota Living with Heart Failure Score
Prazo: 28 days
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Quality of life Minnesota Living with Heart Failure Score and D0 and Day 28
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28 days
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Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Investigadores
- Investigador principal: Faiez Zannad, MD, Centre d'investigation clinique CHU-Nancy
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de junho de 2016
Conclusão Primária (Real)
12 de setembro de 2018
Conclusão do estudo (Real)
12 de setembro de 2018
Datas de inscrição no estudo
Enviado pela primeira vez
17 de maio de 2016
Enviado pela primeira vez que atendeu aos critérios de CQ
20 de maio de 2016
Primeira postagem (Estimativa)
23 de maio de 2016
Atualizações de registro de estudo
Última Atualização Postada (Real)
16 de outubro de 2018
Última atualização enviada que atendeu aos critérios de controle de qualidade
11 de outubro de 2018
Última verificação
1 de outubro de 2018
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- QUID-HF_v5.0_20171120
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
NÃO
Descrição do plano IPD
Individual participant date would be available only by the center via eCRF
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .