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Effect of Pharmacologic Interaction Between ERAs and PDE-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients With PAH (EPIC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2015 by Heidelberg University
Sponsor:
Information provided by (Responsible Party):
Heidelberg University
ClinicalTrials.gov Identifier:
NCT02484807
First received: June 24, 2015
Last updated: June 29, 2015
Last verified: June 2015
  Purpose

The development of disease-targeted medication for the treatment of pulmonary arterial hypertension (PAH) has significantly improved within the last years, leading to the development of 10 approved agents. Combination treatment with Endothelin-Receptor-Antagonists (ERA) and Phosphodiesterase-Type-5-Inibitors (PDE-5-Inhibitor) has become increasingly important for the treatment of PAH. In a recent press release, the results of the AMBITION study reported that an upfront combination treatment immediately after diagnosis leads to a delayed disease progression [4]. Thus, the question if there is a clinically relevant pharmaco-dynamic drug-drug interaction is of rising interest.


Condition Intervention
Pulmonary Arterial Hypertension
Other: no intervention, only observation of different groups

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Effect of Pharmacologic Interaction Between Endothelin-Receptor-Antagonists and Phosphodiesterase-5 Inhibitors on Medication Serum Levels and Clinical Disease Status in Patients Wih Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • Characterisation of medication levels [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    comparison of different combination treatment arms (mean ± standard deviation)


Secondary Outcome Measures:
  • Frequency of borderline medication serum levels or medication levels out of the therapeutic window [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    analysis for the whole cohort

  • Frequency of borderline medication serum levels or medication levels out of the therapeutic window [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    analysis for the different subgroups according to combination treatment (Bosentan + PDE-5-Inhibitor vs. Ambrisentan + PDE-5-Inhibitor vs. Macitentan + PDE-5-Inhibitor)

  • Impact of medication adjustment [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]

    Change of medication serum levels after clinically indicated medication adaptation in patients who received Bosentan + Sildenafil in the beginning and changed the ERA to Macitentan

    1. change of mean levels ± standard deviation
    2. frequency of borderline medication serum levels or medication levels out of the therapeutic window

  • Subgroup analysis: analysis of medication serum levels in patients with pulmonary arterial hypertension associated with connective tissue disease [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    frequency of decreased medication levels; possible sign of maladsorption

  • Clinical relevance WHO functional class [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance 6 minute walking distance [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance NTproBNP [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography systolic pulmonary arterial pressure [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography right ventricular area [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography right atrial area [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography tricuspid annular plane systolic excursion [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography Tei-index [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography left ventricular excentricity index [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance Echocardiography right ventricular pump function [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance blood gas analysis oxygen partial pressure [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance blood gas analysis carbon dioxide partial pressure [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance blood gas analysis oxygen saturation [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance blood gas analysis oxygen supply [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance diffusion capacity DLCO [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance diffusion capacity DLCO/VA [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance clinical symptoms [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: No ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status

  • Clinical relevance adverse events [ Time Frame: baseline vs. 3-6 months ] [ Designated as safety issue: Yes ]
    • Changes of medication levels after adjustment of combination therapy if clinically indicated
    • correlation with clinical routine parameters indicating clinical disease status


Estimated Enrollment: 120
Study Start Date: May 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Bosentan + Sildenafil
Combination treatment with Bosentan + Sildenafil at baseline
Other: no intervention, only observation of different groups
Bosentan + Tadalafil
Combination treatment with Bosentan + Tadalafil at baseline
Other: no intervention, only observation of different groups
Ambrisentan + Sildenafil
Combination treatment with Ambrisentan + Sildenafil at baseline
Other: no intervention, only observation of different groups
Ambrisentan + Tadalafil
Combination treatment with Ambrisentan + Tadalafil at baseline
Other: no intervention, only observation of different groups
Macitentan + Sildenafil
Combination treatment with Macitentan + Sildenafil at baseline
Other: no intervention, only observation of different groups
Macitentan + Tadalafil
Combination treatment with Macitentan + Tadalafil at baseline
Other: no intervention, only observation of different groups

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

patients with pulmonary arterial hypertension receiving disease-targeted combination therapy

Criteria

Inclusion Criteria:

  1. Men and women ≥ 18 years old
  2. Diagnosis of PAH according to ESC/ERS-guidelines: patients with manifest pulmonary arterial hypertension, mean pulmonary arterial pressure ≥25mmHg, measured by right heart catheterization.
  3. Combination treatment with ERA (Bosentan, Ambrisentan or Macitentan) and PDE-5-Inhibitor (Sildenafil or Tadalafil) for more than 3 months.

Exclusion Criteria:

  1. Underage patients
  2. Pregnancy or lactation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02484807

Contacts
Contact: Ekkehard Grünig, MD +496221396 ext 8053 ekkehard.gruenig@med.uni-heidelberg.de

Locations
Germany
Centre for pulmonary hypertension, Thoraxclinic at the University Hospital Heidelberg Recruiting
Heidelberg, Germany, 69126
Contact: Ekkehard Grünig, MD    +496221396 ext 8053    ekkehard.gruenig@med.uni-heidelberg.de   
Sponsors and Collaborators
Heidelberg University
Investigators
Principal Investigator: Ekkehard Grünig, MD Thoraxclinic at the University Hospital Heidelberg
  More Information

Additional Information:
Publications:

Responsible Party: Heidelberg University
ClinicalTrials.gov Identifier: NCT02484807     History of Changes
Other Study ID Numbers: EPIC-01
Study First Received: June 24, 2015
Last Updated: June 29, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Tadalafil
Hypertension
Cardiovascular Diseases
Vascular Diseases
Phosphodiesterase 5 Inhibitors
Sildenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on August 02, 2015