Detecting the Impact of Statin Therapy On Lowering Risk of Venous Thrombo-Embolic Events (DISOLVE) (DISOLVE)
6 de julio de 2018 actualizado por: Steven Ades, University of Vermont
Impact of Rosuvastatin on Risk Markers of Venous Thromboembolism During Systemic Therapy for Advanced Cancer
Patients with cancer have a high risk of developing venous blood clots or thromboembolism (VTE). In an effort to target patients at highest risk of VTE for thromboprophylaxis (protective treatment for blood clots), numerous studies have identified serum biomarkers for risk of future VTE. There is also increasing evidence pointing to a prophylactic effect of statin therapy on the risk of developing VTE in high-risk populations including patients with advanced cancer. The purpose of this research study is to find out whether treatment with rosuvastatin (the study drug) reduces the risk of VTE in patients with cancer receiving chemotherapy. This study is specifically investigating the impact of rosuvastatin therapy on serum biomarkers (D-dimer and others) that indicate a risk for VTE, as well as safety and tolerance of rosuvastatin therapy in this population.
This is a phase II randomized crossover study with two 3-4 week treatment periods during which all enrolled patients will receive 20 mg of rosuvastatin once a day by mouth or a matching placebo tablet. Approximately two tablespoons of blood will be collected for biomarker analysis at the beginning and end of each treatment period. After the first treatment period there will be a 3-5 week break where subjects will undergo a washout. Following this washout period every subject will "crossover" or begin taking the alternative therapy so everyone enrolled will receive the study drug either during the first or the second treatment period. Biomarker levels will be analyzed in both treatment periods and compared to baseline, with every patient acting as their own control.
Descripción general del estudio
Estado
Terminado
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
38
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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-
Vermont
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Burlington, Vermont, Estados Unidos, 05401
- Fletcher Allen Health Care
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-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Adult patients > 18 years old with locally-advanced or metastatic cancers who are about to start or are already receiving any systemic chemotherapy or targeted therapy.
- Estimated overall survival of ≥ 6 months
- Anticipated duration of therapy ≥ 9 weeks (if 3-week cycle) or ≥ 12 weeks (if 2 or 4-week cycle). Systemic therapy is allowed to change if necessary, or to terminate, during this period
Exclusion Criteria:
- Antithrombotic therapy including warfarin, dabigatran, low molecular weight heparin or unfractionated heparin. Patients taking aspirin may participate in this study.
- Anti-angiogenic therapy with thalidomide or lenalidomide. Patients receiving bevacizumab may participate in this study.
- Patients starting hormonal therapy exclusively, such as SERM or aromatase inhibitor therapy for breast cancer, or androgen-ablative therapy for prostate cancer.
- Statin use within 3 months prior to enrolment
- Adjuvant therapy in patients who have already received curative-intent local therapy (surgery or radiotherapy). Patients with glioblastoma starting adjuvant chemotherapy are an exception given the high likelihood of residual disease and risk of VTE in this population.
- Asian descent as assessed by history. If either of the participant's parents is Asian (peoples of East, Southeast, and South Asia), a patient will be excluded due to slower metabolism of the drug and concerns regarding toxicity at the 20 mg dose level.
- Urinary creatinine clearance of less than 40 ml/min based on reported MDRD GFR, present in FAHC metabolic profile reports, during the 14 day screening period.
- AST or ALT elevation of greater than 3X upper limit of normal, during the 14 day screening period.
- Patients with a known history of statin intolerance that was accompanied by severe adverse reaction.
- Patients who are currently participating in another clinical trial involving an investigational medication if there is a known or suspected drug interaction with rosuvastatin or the statin class, or if the investigational agent is known or suspected to be associated with a significantly increased risk of thrombosis.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Prevención
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Rosuvastatin First, Placebo Last
This arm will receive rosuvastatin during the first treatment period followed by placebo in the second treatment period after washout.
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20 mg po od
Otros nombres:
20 mg po od
|
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Experimental: Placebo First, Rosuvastatin Last
This arm will receive placebo during the first treatment period followed by rosuvastatin in the second treatment period after washout.
|
20 mg po od
Otros nombres:
20 mg po od
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
To determine if rosuvastatin therapy reduces the risk of VTE in patients with cancer receiving chemotherapy, as measured by a decrease in D-dimer level with treatment compared to placebo
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor VIII
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
|
To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in soluble P-selectin
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in C-reactive protein
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Peak thrombin generation
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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Adverse Events (CTCAE v4) associated with rosuvastatin therapy
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
Liver toxicity and rhabdomyolysis
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
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Venous thromboembolism
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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Clinical signs of venous thromboembolism
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baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 activity
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
|
To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Plasminogen activator inhibitor-1 protein concentration
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in tissue factor
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
|
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To investigate the impact of rosuvastatin therapy on other established biomarkers of VTE risk in cancer patients receiving chemotherapy as measured by the change in Factor XIa
Periodo de tiempo: baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
|
baseline, 3-4 weeks, 6-9 weeks, 9-13 weeks (ranges depending one treatment period lengths set for each patient at enrollment)
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Steven Ades, MD, MSc, University of Vermont
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Enlaces Útiles
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de marzo de 2012
Finalización primaria (Actual)
1 de julio de 2016
Finalización del estudio (Actual)
1 de septiembre de 2016
Fechas de registro del estudio
Enviado por primera vez
20 de enero de 2012
Primero enviado que cumplió con los criterios de control de calidad
30 de enero de 2012
Publicado por primera vez (Estimar)
2 de febrero de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
10 de julio de 2018
Última actualización enviada que cumplió con los criterios de control de calidad
6 de julio de 2018
Última verificación
1 de julio de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades cardiovasculares
- Enfermedades Vasculares
- Embolia y Trombosis
- Trombosis
- Trombosis venosa
- Tromboembolismo
- Tromboembolismo venoso
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Antimetabolitos
- Agentes Anticolesterolémicos
- Agentes hipolipidémicos
- Agentes reguladores de lípidos
- Inhibidores de la hidroximetilglutaril-CoA reductasa
- Rosuvastatina Cálcica
Otros números de identificación del estudio
- VCC 1110
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