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

5 janvier 2017 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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).

Type d'étude

Observationnel

Inscription (Réel)

13

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

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

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Enfant
  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

Méthode d'échantillonnage

Échantillon de probabilité

Population étudiée

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

La description

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 d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

Cohortes et interventions

Groupe / Cohorte
Intervention / Traitement
Portopulmonary hypertension
Médicament: 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.

Autres noms:
  • Remoduline

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Number of Subjects Who Achieved Hemodynamic Parameters Appropriate for Orthotopic Liver Transplantation Candidacy at Week 24.
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Change in Hemodynamic Parameters (Via Right Heart Catheterization [RHC]) at Rest From Baseline to Week 24
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: Baseline to Weeks 12 and 24
NT-proBNP was assessed at Baseline, Weeks 12 and 24.
Baseline to Weeks 12 and 24

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

United Therapeutics

Collaborateurs

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

Les enquêteurs

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

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 janvier 2011

Achèvement primaire (Réel)

1 avril 2013

Achèvement de l'étude (Réel)

1 avril 2013

Dates d'inscription aux études

Première soumission

8 décembre 2009

Première soumission répondant aux critères de contrôle qualité

8 décembre 2009

Première publication (Estimation)

9 décembre 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

24 février 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

5 janvier 2017

Dernière vérification

1 janvier 2017

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • RIV-PH-414

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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