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A Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension

5 de enero de 2017 actualizado por: United Therapeutics

An Open-Label Study to Assess the Safety and Efficacy of Treprostinil to Facilitate Liver Transplantation in Patients With Portopulmonary Hypertension

This was a multicenter, prospective, observational, open-label study. Patients meeting inclusion/exclusion criteria received treatment with treprostinil as recommended by their treating physicians and were followed according to standard of care. This observational study collected clinical data and biologic specimens from patients who were treated for portopulmonary hypertension (PoPH), with a goal of achieving hemodynamic parameters appropriate for orthotopic liver transplantation candidacy, including mean pulmonary arterial pressure (mPAP) less than 35 mmHg and pulmonary vascular resistance (PVR) less than 3 Wood-units (WU) at Week 24 in patients with severe PoPH.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Descripción detallada

Treprostinil is approved as a continuous subcutaneous (SC) or intravenous (IV) infusion by the FDA for the treatment of WHO group I PAH with New York Heart Association (NYHA) Functional Class II, III or IV symptomatology. To date, treprostinil has not been studied in the setting of PoPH; however, it is commonly prescribed in this setting. This was an observational, open-label, multicenter study which documented the safety and efficacy profile of this agent in PoPH to facilitate orthotopic liver transplantation (OLT).

Tipo de estudio

De observación

Inscripción (Actual)

13

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

  • Estados Unidos
    • California
      • Los Angeles, California, Estados Unidos, 90024
        • University of California, Los Angeles
    • Georgia
      • Atlanta, Georgia, Estados Unidos, 30322
        • Emory Univeristy
    • Massachusetts
      • Boston, Massachusetts, Estados Unidos, 02115
        • Brigham and Women's Hospital
    • Texas
      • Dallas, Texas, Estados Unidos, 75235
        • University of Texas, Southwestern Medical Center

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

  • Niño
  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Método de muestreo

Muestra de probabilidad

Población de estudio

Subjects were recruited from 4 liver transplantation centers in the US, referred for portopulmonary hypertension.

Descripción

Inclusion Criteria:

  • Patients must:

    1. Had portal hypertension.
    2. Be otherwise suitable candidates for OLT.
    3. Had severe pulmonary arterial hypertension (PAH) defined as a resting mean pulmonary arterial pressure (mPAP) >35 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood Units (WU) by right heart catheterization (RHC) performed as part of standard of care evaluation within 90 days of enrollment.
    4. Treprostinil therapy must be recommended by the treating physician per standard of care.
    5. Be NYHA Functional Class II, III, or IV.
    6. Had pulmonary capillary wedge (PCW) pressure ≤18 mmHg and transpulmonary gradient (TPG) ≥15 mmHg.

Exclusion Criteria:

  • Patients must not:

    1. Had received any any investigational therapy as part of a clinical trial for any indication within 30 days prior to enrollment.
    2. Had a change in dose of treatment for PAH (bosentan [Tracleer], ambrisentan [Letairis], tadalafil [Adcirca], or sildenafil [Revatio]), within 30 days prior to enrollment. That is, subjects may have been treated with any of these agents provided the dose was stable for at least 30 days prior to enrollment.
    3. Had renal failure requiring hemodialysis.

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

Cohortes e Intervenciones

Grupo / Cohorte
Intervención / Tratamiento
Portopulmonary hypertension
Droga: Treprostinil

Remodulin is supplied in concentrations of 1, 2.5 , 5, and 10 mg/mL and can be administered as supplied or diluted for intravenous (IV) infusion prior to administration.

Remodulin is indicated for subcutaneous (SC) or IV use only as a continuous infusion. Remodulin is preferably infused subcutaneously, but can be administered by a central IV line if the SC route is not tolerated. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min.

Otros nombres:
  • Remodulina

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.
Periodo de tiempo: 24 Weeks
The primary efficacy endpoint was the number of subjects who achieved a mean pulmonary arterial pressure (mPAP) less than 35 mmHg and a pulmonary vascular resistance (PVR) less than 3 Wood units (WU) at Week 24 in patients with severe portopulmonary hypertension (PoPH).
24 Weeks

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24
Periodo de tiempo: 24 weeks
The change in hemodynamic parameters (including systolic pulmonary arterial pressure [PAPs], diastolic pulmonary arterial pressure [PAPd], mean pulmonary arterial pressure [mPAP], and transpulmonary gradient [TPG]) was evaluated at rest from Baseline to Week 24. The median change in hemodynamic parameters from Baseline to Week 24 via right-heart catheterization (RHC) is presented.
24 weeks
Change in Heart Rate at Rest From Baseline to Week 24
Periodo de tiempo: 24 weeks
The change in heart rate was evaluated at rest from Baseline to Week 24.
24 weeks
Change in Cardiac Output at Rest From Baseline to Week 24
Periodo de tiempo: 24 weeks
The change in cardiac output was evaluated at rest from Baseline to Week 24. The median change in cardiac output from Baseline to Week 24 is presented.
24 weeks
Change in Arterial and Venous Oxygen Saturation at Rest From Baseline to Week 24
Periodo de tiempo: 24 weeks
The change in arterial and venous oxygen saturation was evaluated at rest from Baseline to Week 24.
24 weeks
Change in Pulmonary Vascular Resistance (PVR) at Rest From Baseline to Week 24
Periodo de tiempo: 24 weeks
The change in pulmonary vascular resistance (PVR) was evaluated at rest from Baseline to Week 24.
24 weeks
Change in 6-minute Walk Distance (6MWD) From Baseline to Weeks 12 and 24.
Periodo de tiempo: Baseline and Weeks 12 and 24
The 6-Minute Walk Test was conducted at Screening, Baseline prior to starting study drug and at least 24 hours after the Screening test, and during the Treatment Phase at Weeks 12 and 24.
Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Atrium and Right Ventricle Area) From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline and Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricle Diameter) From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline and Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Right Ventricular Systolic Pressure) From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline and Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Baseline and Weeks 12 and 24
Change in Echocardiogram Parameters (Tricuspid Annular Plane Systolic Excursion) From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline and Weeks 12 and 24
Standard transthoracic echocardiogram with continuous wave Doppler and color flow imaging was completed at Screening. All patients who were enrolled in this study underwent an echocardiogram within 30 days of enrollment as well as repeat echocardiograms on Weeks 12 and 24.
Baseline and Weeks 12 and 24
Change in Quality of Life From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline and Weeks 12 and 24
The 36-item Short Form Survey (SF-36) is a health related quality of life instrument, which measures dimensions of physical and social roles and functioning, mental health, vitality, and pain. Items are scored on a 0 to 100 range so that the lowest scores represent the highest disability. The quality of life assessment was conducted at Baseline and Weeks 12 and 24 and the change from Baseline to Weeks 12 and 24 is presented.
Baseline and Weeks 12 and 24
Change in Plasma Brain N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) From Baseline to Weeks 12 and 24
Periodo de tiempo: Baseline to Weeks 12 and 24
NT-proBNP was assessed at Baseline, Weeks 12 and 24.
Baseline to Weeks 12 and 24

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

United Therapeutics

Colaboradores

University of California, Los Angeles
Emory University
Brigham and Women's Hospital
University of Texas

Investigadores

  • Director de estudio: Rajan Saggar, MD, University of California, Los Angeles
  • Director de estudio: Micah Fisher, MD, Emory University
  • Director de estudio: Aaron Waxman, MD, PhD, Brigham and Women's Hospital
  • Director de estudio: Sonja Bartolome, MD, UT Southwestern Medical Center

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 enero de 2011

Finalización primaria (Actual)

1 de abril de 2013

Finalización del estudio (Actual)

1 de abril de 2013

Fechas de registro del estudio

Enviado por primera vez

8 de diciembre de 2009

Primero enviado que cumplió con los criterios de control de calidad

8 de diciembre de 2009

Publicado por primera vez (Estimar)

9 de diciembre de 2009

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

24 de febrero de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

5 de enero de 2017

Última verificación

1 de enero de 2017

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • RIV-PH-414

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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