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CompletedNCT02070991MELODY-1Updated May 15, 2019Results posted

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

A Phase 2 interventional study of Macitentan and Placebo in Pulmonary Hypertension, sponsored by Actelion. Completed at 32 sites in 11 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-05-15.

Sponsored by Actelion · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
63
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Pulmonary Hypertension

Keywords

  • pre- and post-capillary pulmonary hypertension
  • CpcPH
03

In context

Hypertension, Pulmonary

1,105 studies on the registry are indexed under Hypertension, Pulmonary; 234 are open to participants now.

This study's enrollment of 63 is above the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.

Browse Hypertension, Pulmonary studies →

Lead sponsor

Actelion is the lead sponsor of 140 studies on the registry; 1 is open to participants now.

Of its 27 completed or terminated interventional studies of FDA-regulated products, 24 (89%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
63 participants (actual)

Study arms

  • Experimental
    Macitentan

    oral tablet, 10 mg once daily.

    Drug: Macitentan

  • Placebo comparator
    Placebo

    Matching placebo, once daily.

    Drug: Placebo

Interventions

  • DrugMacitentan

    oral tablet, 10 mg once daily

    Also known as: ACT-064992

  • DrugPlacebo

    matching placebo

    Also known as: matching placebo

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day

Secondary outcomes

  1. 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)

  2. 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).

    Time frame: From randomization up to end of treatment period (Week 12)

  3. Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)

    Time frame: From randomization up to end of treatment period (Week 12)

  4. Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)

    Time frame: From randomization up to end of treatment period (Week 12)

  5. Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)

    Time frame: From randomization up to end of treatment period (Week 12)

  6. Change From Baseline to Week 12 in Cardiac Index (CI)

    Time frame: From randomization up to end of treatment period (Week 12)

  7. 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)

07

Results

Posted May 15, 2019

Participant flow

Participants were screened from 28 sites across Europe and North America in 11 countries (Austria, Belgium, Canada, Czech Republic, Germany, France, Israel, Italy, Spain, Switzerland, USA).

Participant flow — Overall Study
MilestoneMacitentanPlacebo
Started3132
Completed2832
Not completed30
Withdrew: Death20
Withdrew: Withdrawal by subject10

Outcome measures

PrimaryNumber 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.

Time frame:
From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day
Reported as:
Count of participants · Participants
Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment
ParticipantsMacitentanPlacebo
Total participants with at least one condition74
Participants with fluid retention73
Participants with worsening in NYHA FC12
Participants with both conditions11
Statistical analysis
  • Macitentan vs Placebo · Fisher Exact · p = 0.3372 · Difference between maci. and placebo: 10.08 · 95% CI -15.07 to 33.26
SecondaryNT-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)
Reported as:
Geometric mean · percentage of baseline NT-proBNP
NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest
percentage of baseline NT-proBNPMacitentanPlacebo
NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest91.56 (72.37 to 115.83)118.90 (92.53 to 152.78)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (ratio of geom. means): 0.77 · 95% CI 0.55 to 1.08
SecondaryPVR 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).

Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Geometric mean · percentage of baseline PVR
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest
percentage of baseline PVRMacitentanPlacebo
PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest66.31 (56.15 to 78.30)71.23 (51.35 to 98.81)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (ratio of geom. means): 0.93 · 95% CI 0.64 to 1.36
SecondaryChange From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)
Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Mean · mmHg
Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP)
mmHgMacitentanPlacebo
mPAP at baseline44.6 (40.7 to 48.6)45.9 (41.7 to 50.1)
mPAP at Week 1241.1 (36.2 to 46.0)42.1 (37.5 to 46.7)
Change in mPAP from baseline to Week 12-3.5 (-6.1 to -0.9)-3.8 (-7.5 to -0.1)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (mean change from bl): 0.3 · 95% CI -4.3 to 4.9
SecondaryChange From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Mean · mmHg
Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP)
mmHgMacitentanPlacebo
mRAP at baseline12.1 (10.0 to 14.3)13.0 (11.0 to 14.9)
mRAP at Week 1211.2 (8.7 to 13.8)11.3 (9.2 to 13.5)
Change in mRAP from baseline to Week 12-0.9 (-3.5 to 1.7)-1.6 (-3.3 to 0.0)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (mean change from bl): 0.7 · 95% CI -2.2 to 3.6
SecondaryChange From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)
Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Mean · mmHg
Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP)
mmHgMacitentanPlacebo
PAWP at baseline19.1 (17.4 to 20.7)19.7 (18.2 to 21.2)
PAWP at Week 1219.9 (16.6 to 23.1)20.8 (17.8 to 23.7)
Change in PAWP from baseline to Week 120.8 (-2.3 to 3.9)1.1 (-1.6 to 3.8)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (mean change from bl): -0.3 · 95% CI -4.2 to 3.7
SecondaryChange From Baseline to Week 12 in Cardiac Index (CI)
Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Mean · L/min/m^2
Change From Baseline to Week 12 in Cardiac Index (CI)
L/min/m^2MacitentanPlacebo
CI at baseline2.32 (2.02 to 2.61)2.33 (2.09 to 2.57)
CI at Week 122.69 (2.36 to 3.02)2.30 (2.03 to 2.57)
Change in CI from baseline to Week 120.37 (0.14 to 0.60)-0.03 (-0.22 to 0.16)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (mean change from bl): 0.40 · 95% CI 0.11 to 0.69
SecondaryChange From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)
Time frame:
From randomization up to end of treatment period (Week 12)
Reported as:
Mean · mmHg
Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG)
mmHgMacitentanPlacebo
DPG at baseline11.8 (9.0 to 14.5)11.4 (9.5 to 13.2)
DPG at Week 127.0 (4.2 to 9.8)7.0 (3.7 to 10.4)
Change in DPG from baseline to Week 12-4.8 (-7.2 to -2.3)-4.3 (-7.5 to -1.1)
Statistical analysis
  • Macitentan vs Placebo · Treatment effect (mean change from bl): -0.4 · 95% CI -4.5 to 3.6

Adverse events

Collected over From study treatment initiation up to 30 days after study treatment discontinuation (Week 12 + 30 days). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Macitentan2/31 (6.5%)11/31 (35.5%)16/31 (51.6%)
Placebo0/32 (0%)6/32 (18.8%)15/32 (46.9%)
Most frequent serious events
Showing 10 of 21
Most frequent serious events
EventMacitentanPlacebo
PneumoniaInfections and infestations2/310/32
Cardiac failure acuteCardiac disorders1/310/32
Cardiac failure congestiveCardiac disorders1/311/32
Cardiorenal syndromeCardiac disorders1/310/32
Left ventricular failureCardiac disorders1/310/32
Right ventricular failureCardiac disorders1/311/32
Ventricular tachycardiaCardiac disorders1/310/32
Mouth haemorrhageGastrointestinal disorders1/310/32
Oedema peripheralGeneral disorders1/311/32
Sudden deathGeneral disorders1/310/32
Most frequent other events
Showing 10 of 19
Most frequent other events
EventMacitentanPlacebo
DyspnoeaRespiratory, thoracic and mediastinal disorders3/314/32
DiarrhoeaGastrointestinal disorders3/311/32
Oedema peripheralGeneral disorders2/313/32
AnaemiaBlood and lymphatic system disorders2/310/32
Mitral valve incompetenceCardiac disorders2/310/32
Respiratory tract infectionInfections and infestations2/310/32
Haemoglobin decreasedInvestigations2/310/32
Fluid retentionMetabolism and nutrition disorders2/310/32
HypokalaemiaMetabolism and nutrition disorders2/310/32
Hepatic neoplasmNeoplasms benign, malignant and unspecified (incl cysts and polyps)2/310/32

Baseline characteristics

Age, Continuous
Age, Continuous(Years)MacitentanPlaceboTotal
Median70.0 (67.0 to 73.0)72.0 (68.0 to 75.5)71.0 (67.0 to 75.0)
Age, Customized
Age, Customized(Participants)MacitentanPlaceboTotal
18-64 years538
65-84 years262854
≥ 85 years011
Sex: Female, Male
Sex: Female, Male(Participants)MacitentanPlaceboTotal
Female251641
Male61622
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)MacitentanPlaceboTotal
Hispanic or Latino112
Not Hispanic or Latino303161
Unknown or Not Reported000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)MacitentanPlaceboTotal
Black or African American011
American Indian or Alaska Native101
White303060
Other011
Time from Left Ventricular Dysfunction (LVD) diagnosis
Time from Left Ventricular Dysfunction (LVD) diagnosis(years)MacitentanPlaceboTotal
Median0.9 (0.1 to 5.4)1.5 (0.4 to 3.4)1.3 (0.2 to 4.2)
Time from Combined pre- and post-capillary Pulmonary Hypertension (CpcPH) diagnosis
Time from Combined pre- and post-capillary Pulmonary Hypertension (CpcPH) diagnosis(years)MacitentanPlaceboTotal
Median0.2 (0.0 to 1.4)0.2 (0.0 to 0.5)0.2 (0.0 to 0.5)
New York Heart Association (NYHA) Functional Class at baseline
New York Heart Association (NYHA) Functional Class at baseline(Participants)MacitentanPlaceboTotal
Class I000
Class II51015
Class III262248
Class IV000

10 further baseline measures are reported on the registry.

08

Study locations

32 sites
  • Kentuckiana Pulmonary Associates
    Louisville, Kentucky 40202, United States
  • Boston University School of Medicine
    Boston, Massachusetts 02118, United States
  • University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program
    Ann Arbor, Michigan 48109, United States
  • Washington University School of Medicine - Center for Advanced Med
    Saint Louis, Missouri, United States
  • The Lindner Clinical Trial Center
    Cincinnati, Ohio, United States
  • Houston Methodist Hospital - Heart Failure/Pulm Hypertension
    Houston, Texas, United States
  • Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung
    Linz, Austria
  • Medical University of Vienna and AKH Cardiology
    Vienna, A-1090, Austria
  • Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie
    Brussels, 1070, Belgium
  • University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie
    Leuven, 3000, Belgium
  • Vancouver General Hospital - The Lung
    Vancouver, Canada
  • FN Brno-Bohunice, I. interní kardiologická klinika
    Brno, Czechia
  • FN Olomouc, 1. Interní klinika - kardiologická
    Olomouc, Czechia
  • IKEM (Institut klinické a experimentální medicíny, Institute for Clinical and Experimental Medicine)
    Praha, Czechia
  • Lékařská fakulta a Všeobecná fakultní nemocnice v Praze, II. Interní klinika kardiologie a angiologie
    Praha, Czechia
  • Hôpital Charles Nicolle Service de Cardiologie
    Rouen cedex, France
  • DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie
    Berlin, Germany
  • Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie
    Kiel, Germany
  • Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin)
    Köln, Germany
  • Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie
    Munich, Germany
  • Carmel Medical Center, Pulmonary Unit
    Haifa, 34362, Israel
  • Institute of Pulmonology Hadassah Medical Centre : Ein Karem
    Jerusalem, 91120, Israel
  • Kaplan Medical Centre / Pulmonary Institute and Department of Medicine
    Rehovot, 76100, Israel
  • The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise
    Tel-Hashomer, 52621, Israel
  • A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia
    Bologna, 40138, Italy
  • Ospedali Riuniti Di Trieste
    Trieste, 34149, Italy
  • Hospital Vall d´Hebron Servicio de Cardiologia
    Barcelona, 08035, Spain
  • Hospital Clinic Servicio de Cardiologia
    Barcelona, 08036, Spain
  • Hospital Reina Sofia Servicio de Cardiologia
    Cordoba, 14004, Spain
  • Hospital Universitario 12 Octubre Servicio de Cardiología
    Madrid, 28041, Spain
  • Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern
    Bern, Switzerland
  • Centre Hospitalier Universitaire Vaudois Service de Cardiologie
    Lausanne, Switzerland
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 15, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02070991
Lead sponsor
Actelion
Responsible party
Sponsor
First posted
Feb 25, 2014
Start date
Jul 1, 2014
Primary completion
Nov 1, 2015
Completion
Nov 1, 2015
Results posted
May 15, 2019
Last update
May 15, 2019

Study contacts

Sébastien Roux, PhD
study chair · Actelion

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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