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Clinical Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction (MELODY-1)

Primary Purpose

Pulmonary Hypertension

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Macitentan
Placebo
Sponsored by
Actelion
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension focused on measuring pre- and post-capillary pulmonary hypertension, CpcPH

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Males and Females >=18 years of age
  2. Subjects with combined pre-and post-capillary Pulmonary Hypertension (CpcPH) due to left ventricular dysfunction (subset of WHO groups 2.1 and 2.2)
  3. Optimized diuretic therapy

Exclusion Criteria:

  1. Types of Pulmonary Hypertension other than WHO groups 2.1 and 2.2 (Nice classification)
  2. Administration of PAH-specific therapy (i.e., Endothelin receptor antagonists (ERAs), Prostanoids, Phosphodiesterase 5 (PDE-5) inhibitors, guanylate cyclase stimulators)

Sites / Locations

  • Kentuckiana Pulmonary Associates
  • Boston University School of Medicine
  • University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program
  • Washington University School of Medicine - Center for Advanced Med
  • The Lindner Clinical Trial Center
  • Houston Methodist Hospital - Heart Failure/Pulm Hypertension
  • Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung
  • Medical University of Vienna and AKH Cardiology
  • Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie
  • University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
  • Vancouver General Hospital - The Lung
  • FN Brno-Bohunice, I. interní kardiologická klinika
  • FN Olomouc, 1. Interní klinika - kardiologická
  • IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)
  • Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie
  • Hôpital Charles Nicolle Service de Cardiologie
  • DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie
  • Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie
  • Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)
  • Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie
  • Carmel Medical Center, Pulmonary Unit
  • Institute of Pulmonology Hadassah Medical Centre : Ein Karem
  • Kaplan Medical Centre / Pulmonary Institute and Department of Medicine
  • The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise
  • A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia
  • Ospedali Riuniti Di Trieste
  • Hospital Vall d´Hebron Servicio de Cardiologia
  • Hospital Clinic Servicio de Cardiologia
  • Hospital Reina Sofia Servicio de Cardiologia
  • Hospital Universitario 12 Octubre Servicio de Cardiología
  • Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern
  • Centre Hospitalier Universitaire Vaudois Service de Cardiologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Macitentan

Placebo

Arm Description

oral tablet, 10 mg once daily.

Matching placebo, once daily.

Outcomes

Primary Outcome Measures

Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment
The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline.

Secondary Outcome Measures

NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest
Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC).
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)
Change From Baseline to Week 12 in Cardiac Index (CI)
Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)

Full Information

First Posted
February 21, 2014
Last Updated
April 24, 2019
Sponsor
Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT02070991
Brief Title
Clinical Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction
Acronym
MELODY-1
Official Title
A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group, 12-week Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction
Study Type
Interventional

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Completed
Study Start Date
July 1, 2014 (Actual)
Primary Completion Date
November 1, 2015 (Actual)
Study Completion Date
November 1, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Study to evaluate if macitentan is safe and tolerable enough to be used for treatment of subjects with combined pre- and post-capillary pulmonary hypertension (CpcPH) due to left ventricular dysfunction.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension
Keywords
pre- and post-capillary pulmonary hypertension, CpcPH

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
63 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Macitentan
Arm Type
Experimental
Arm Description
oral tablet, 10 mg once daily.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo, once daily.
Intervention Type
Drug
Intervention Name(s)
Macitentan
Other Intervention Name(s)
ACT-064992
Intervention Description
oral tablet, 10 mg once daily
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
matching placebo
Intervention Description
matching placebo
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment
Description
The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline.
Time Frame
From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day
Secondary Outcome Measure Information:
Title
NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest
Time Frame
From randomization up to end of treatment period (Week 12)
Title
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest
Description
Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC).
Time Frame
From randomization up to end of treatment period (Week 12)
Title
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)
Time Frame
From randomization up to end of treatment period (Week 12)
Title
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
Time Frame
From randomization up to end of treatment period (Week 12)
Title
Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)
Time Frame
From randomization up to end of treatment period (Week 12)
Title
Change From Baseline to Week 12 in Cardiac Index (CI)
Time Frame
From randomization up to end of treatment period (Week 12)
Title
Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)
Time Frame
From randomization up to end of treatment period (Week 12)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Males and Females >=18 years of age Subjects with combined pre-and post-capillary Pulmonary Hypertension (CpcPH) due to left ventricular dysfunction (subset of WHO groups 2.1 and 2.2) Optimized diuretic therapy Exclusion Criteria: Types of Pulmonary Hypertension other than WHO groups 2.1 and 2.2 (Nice classification) Administration of PAH-specific therapy (i.e., Endothelin receptor antagonists (ERAs), Prostanoids, Phosphodiesterase 5 (PDE-5) inhibitors, guanylate cyclase stimulators)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sébastien Roux, PhD
Organizational Affiliation
Actelion
Official's Role
Study Chair
Facility Information:
Facility Name
Kentuckiana Pulmonary Associates
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Boston University School of Medicine
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University School of Medicine - Center for Advanced Med
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
The Lindner Clinical Trial Center
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
Houston Methodist Hospital - Heart Failure/Pulm Hypertension
City
Houston
State/Province
Texas
Country
United States
Facility Name
Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung
City
Linz
Country
Austria
Facility Name
Medical University of Vienna and AKH Cardiology
City
Vienna
ZIP/Postal Code
A-1090
Country
Austria
Facility Name
Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Vancouver General Hospital - The Lung
City
Vancouver
Country
Canada
Facility Name
FN Brno-Bohunice, I. interní kardiologická klinika
City
Brno
Country
Czechia
Facility Name
FN Olomouc, 1. Interní klinika - kardiologická
City
Olomouc
Country
Czechia
Facility Name
IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)
City
Praha
Country
Czechia
Facility Name
Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie
City
Praha
Country
Czechia
Facility Name
Hôpital Charles Nicolle Service de Cardiologie
City
Rouen cedex
Country
France
Facility Name
DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie
City
Berlin
Country
Germany
Facility Name
Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie
City
Kiel
Country
Germany
Facility Name
Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)
City
Köln
Country
Germany
Facility Name
Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie
City
Munich
Country
Germany
Facility Name
Carmel Medical Center, Pulmonary Unit
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Institute of Pulmonology Hadassah Medical Centre : Ein Karem
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Kaplan Medical Centre / Pulmonary Institute and Department of Medicine
City
Rehovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise
City
Tel-Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Ospedali Riuniti Di Trieste
City
Trieste
ZIP/Postal Code
34149
Country
Italy
Facility Name
Hospital Vall d´Hebron Servicio de Cardiologia
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Clinic Servicio de Cardiologia
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital Reina Sofia Servicio de Cardiologia
City
Cordoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
Hospital Universitario 12 Octubre Servicio de Cardiología
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern
City
Bern
Country
Switzerland
Facility Name
Centre Hospitalier Universitaire Vaudois Service de Cardiologie
City
Lausanne
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

Clinical Study to Evaluate the Safety and Tolerability of Macitentan in Subjects With Combined Pre- and Post-capillary Pulmonary Hypertension (CpcPH) Due to Left Ventricular Dysfunction

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