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- Ensaio Clínico NCT00461630
Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE (HPS2-THRIVE)
A Randomized Trial of the Long-term Clinical Effects of Raising HDL Cholesterol With Extended Release Niacin/Laropiprant
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
Cardiovascular disease is one of the leading causes of morbidity and mortality in the United Kingdom (UK), as well as in the developed and the developing world. Finding new and safe treatments to reduce the burden of heart disease and strokes is therefore an important contribution to public health and in the wider public interest. HPS2-THRIVE aims to find out whether by combining niacin (a drug that has been available for 50 years) with a new drug laropiprant(which reduces the side-effects of niacin) is beneficial. All participants in HPS2-THRIVE will have established cardiovascular disease and therefore be at very high risk of recurrent vascular events (myocardial infarction, stroke or the need for arterial revascularisation). Two of the most important risk factors for recurrent events in such patients are the blood levels of LDL cholesterol with a positive association, and HDL cholesterol levels with a negative association.
HDL cholesterol has long been known to have a strong inverse correlation with coronary heart disease (CHD) risk. But, randomized trial evidence for beneficial effects from raising HDL cholesterol is limited. One of the most effective HDL-raising agents is niacin but the tolerability of niacin has been severely limited by flushing and cutaneous side-effects, which appear to be mediated largely by prostaglandin D. Laropiprant is a selective prostaglandin D receptor antagonist that substantially reduces the frequency and intensity of niacin-induced flushing. Daily oral doses of extended release (ER) niacin plus Laropiprant 2g(formerly MK-0524A) have been well tolerated in early studies and increase HDL cholesterol by 20-25%. The trial will assess whether this increase in HDL cholesterol translates into clinical benefit as is expected from the observational evidence. In addition, all participants will also be provided with effective LDL-lowering therapy, as either simvastatin 40mg daily alone or with ezetimibe 10mg daily in a combination tablet.
The complementary effects on the HDL (good) and LDL (bad) cholesterol produced by extended release niacin/laropiprant 2 g daily and simvastatin 40 mg with or without ezetimibe 10 mg should provide an excellent treatment option for patients with vascular disease. However, no trials so far have demonstrated clearly that raising HDL cholesterol produces the expected reduction in cardiovascular risk. If HPS2-THRIVE is able to demonstrate reliably that raising HDL cholesterol reduces the risk of further cardiovascular events then this will be relevant to hundreds of millions of people worldwide.
Tipo de estudo
Inscrição (Real)
Estágio
- Fase 3
Contactos e Locais
Locais de estudo
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Oxford, Reino Unido, OX3 7LF
- Clinical Trial Service Unit, University of Oxford
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- History of myocardial infarction; or
- Cerebrovascular atherosclerotic disease (history of presumed ischaemic stroke, transient ischaemic attack or carotid revascularisation)
- Peripheral arterial disease (i.e. intermittent claudication or history of revascularisation); or
- Diabetes mellitus with any of the above or with other evidence of symptomatic coronary heart disease (i.e. stable or unstable angina, or a history of coronary revascularisation or acute coronary syndrome).
Exclusion Criteria:
- Age <50 or >80 years at invitation to Screening;
- Less than 3 months since presentation with acute myocardial infarction, coronary syndrome or stroke (but such patients may be entered later, if appropriate);
- Planned revascularisation procedure within 3 months after randomization (but such patients may be entered later, if appropriate);
- Definite history of chronic liver disease, or abnormal liver function (i.e. Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN). (Note: Patients with a history of acute hepatitis are eligible provided this ALT limit is not exceeded);
- Breathlessness at rest for any reason;
- Severe renal insufficiency (i.e. creatinine >200 µmol/L);
- Evidence of active inflammatory muscle disease (e.g. dermatomyositis, polymyositis), or Creatine kinase (CK) >3 times upper limit of normal (3xULN);
- Previous significant adverse reaction to a statin, ezetimibe, niacin or laropiprant;
- Active peptic ulcer disease;
- Concurrent treatment with:
- fibric acid derivative ("fibrate")
- niacin (nicotinic acid) at doses more than 100 mg daily
- ezetimibe in combination with either simvastatin 80 mg, or atorvastatin 20-80 mg, or rosuvastatin 10-40 mg daily
- any potent cytochrome P450 3A4 (CYP3A4) inhibitor, including: macrolide antibiotics (erythromycin, clarithromycin, telithromycin); systemic use of imidazole or triazole antifungals (e.g. itraconazole, ketoconazole); protease inhibitors (antiretroviral drugs for HIV infection); and nefazodone
- ciclosporin
- amiodarone
- verapamil
- danazol (Note: Patients who are temporarily taking such drugs may be re-screened when they discontinue them, if considered appropriate.);
- Known to be poorly compliant with clinic visits or prescribed medication;
- Medical history that might limit the individual's ability to take trial treatments for the duration of the study (e.g. severe respiratory disease, history of cancer or evidence of spread within last 5 years other than non-melanoma skin cancer, or recent history of alcohol or substance misuse)
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: ER niacin/laropiprant
1 g ER niacin plus 20 mg laropiprant per tablet.
2 tablets orally per day.
With either 40 mg simvastatin tablet or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily
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Outros nomes:
40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Outros nomes:
10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Outros nomes:
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Comparador Ativo: Placebo
Placebo (for ER niacin/laropiprant) 2 tablets orally per day.
With either 40 mg simvastatin tablet orally per day or ezetimibe/simvastatin (10 mg/40 mg) in single tablet taken once daily
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40 mg simvastatin tablet orally per day as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Outros nomes:
10 mg ezetimibe plus 40 mg simvastatin in single tablet taken once daily as background LDL-lowering treatment allocated at entry based on previous statin treatment and total cholesterol level
Outros nomes:
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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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Major Vascular Event
Prazo: During scheduled treatment period (median duration 3.9 years)
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Non-fatal myocardial infarction or coronary death, non-fatal or fatal stroke, or revascularisation
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During scheduled treatment period (median duration 3.9 years)
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Major Coronary Events
Prazo: During scheduled treatment period (median duration 3.9 years)
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Non-fatal myocardial infarction (MI) or coronary death
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During scheduled treatment period (median duration 3.9 years)
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Stroke
Prazo: During scheduled treatment period (median duration 3.9 years)
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Fatal or non-fatal
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During scheduled treatment period (median duration 3.9 years)
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Coronary or Non-coronary Revascularisation
Prazo: During scheduled treatment period (median duration 3.9 years)
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During scheduled treatment period (median duration 3.9 years)
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Mortality
Prazo: During scheduled treatment period (median duration 3.9 years)
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All-cause mortality
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During scheduled treatment period (median duration 3.9 years)
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Jane Armitage, Clinical Trial Service Unit, University of Oxford
- Investigador principal: Colin Baigent, Clinical Trial Service Unit, University of Oxford
- Investigador principal: Zhengming Chen, Clinical Trial Service Unit, University of Oxford
- Investigador principal: Martin Landray, Clinical Trial Service Unit, University of Oxford
Publicações e links úteis
Publicações Gerais
- HPS2-THRIVE Collaborative Group; Haynes R, Chen F, Wincott E, Dayanandan R, Lay MJ, Parish S, Bowman L, Landray MJ, Armitage J. Investigating modifications to participant information materials to improve recruitment into a large randomized trial. Trials. 2019 Dec 5;20(1):681. doi: 10.1186/s13063-019-3779-4.
- Haynes R, Valdes-Marquez E, Hopewell JC, Chen F, Li J, Parish S, Landray MJ, Armitage J; HPS2-THRIVE Collaborative Group; HPS2-THRIVE Writing Committee members; HPS2-THRIVE Steering Committee members. Serious Adverse Effects of Extended-release Niacin/Laropiprant: Results From the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Trial. Clin Ther. 2019 Sep;41(9):1767-1777. doi: 10.1016/j.clinthera.2019.06.012. Epub 2019 Aug 22.
- Offer A, Arnold M, Clarke R, Bennett D, Bowman L, Bulbulia R, Haynes R, Li J, Hopewell JC, Landray M, Armitage J, Collins R, Parish S; Heart Protection Study (HPS), Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH), and Treatment of HDL (High-Density Lipoprotein) to Reduce the Incidence of Vascular Events (HPS2-THRIVE) Collaborative Grou. Assessment of Vascular Event Prevention and Cognitive Function Among Older Adults With Preexisting Vascular Disease or Diabetes: A Secondary Analysis of 3 Randomized Clinical Trials. JAMA Netw Open. 2019 Mar 1;2(3):e190223. doi: 10.1001/jamanetworkopen.2019.0223. Erratum In: JAMA Netw Open. 2019 Mar 1;2(3):e192236.
- Parish S, Hopewell JC, Hill MR, Marcovina S, Valdes-Marquez E, Haynes R, Offer A, Pedersen TR, Baigent C, Collins R, Landray M, Armitage J; HPS2-THRIVE Collaborative Group. Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study. Circ Genom Precis Med. 2018 Feb;11(2):e001696. doi: 10.1161/CIRCGEN.117.001696.
- Kent S, Haynes R, Hopewell JC, Parish S, Gray A, Landray MJ, Collins R, Armitage J, Mihaylova B; HPS2-THRIVE Collaborative Group. Effects of Vascular and Nonvascular Adverse Events and of Extended-Release Niacin With Laropiprant on Health and Healthcare Costs. Circ Cardiovasc Qual Outcomes. 2016 Jul;9(4):348-54. doi: 10.1161/CIRCOUTCOMES.115.002592. Epub 2016 Jul 12.
- HPS2-THRIVE Collaborative Group; Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, Tomson J, Wallendszus K, Craig M, Jiang L, Collins R, Armitage J. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014 Jul 17;371(3):203-12. doi: 10.1056/NEJMoa1300955.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo
Conclusão Primária (Real)
Conclusão do estudo (Real)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Estimativa)
Atualizações de registro de estudo
Última Atualização Postada (Estimativa)
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
- Doenças Vasculares
- Distúrbios do Metabolismo da Glicose
- Doenças Metabólicas
- Arteriosclerose
- Doenças Arteriais Oclusivas
- Doenças do Sistema Endócrino
- Aterosclerose
- Doenças cardíacas
- Doença arterial coronária
- Isquemia do miocárdio
- Doença cardíaca
- Doenças cardiovasculares
- Diabetes Mellitus
- Doença arterial periférica
- Doenças Vasculares Periféricas
- Efeitos Fisiológicos das Drogas
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Vasodilatadores
- Inibidores Enzimáticos
- Antimetabólitos
- Micronutrientes
- Agentes Anticolesterêmicos
- Agentes Hipolipidêmicos
- Agentes Reguladores Lipídicos
- Inibidores da hidroximetilglutaril-CoA redutase
- Vitaminas
- Complexo de Vitamina B
- Sinvastatina
- Niacina
- Ezetimiba
- Combinação de Medicamentos Ezetimiba e Sinvastatina
Outros números de identificação do estudo
- CTSUTHRIVE1
- ISRCTN29503772
- 2006-001885-17 (Número EudraCT)
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 .
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