Clinical Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation (SOPRANO)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT02554903 |
|
Recruitment Status :
Completed
First Posted : September 18, 2015
Last Update Posted : April 15, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
STUDY OBJECTIVES Primary objective To evaluate the effect of macitentan 10 mg on pulmonary vascular resistance (PVR) as compared to placebo in subjects with pulmonary hypertension (PH) after left ventricular assist device (LVAD) implantation.
Secondary objectives To evaluate the effect of macitentan 10 mg as compared to placebo on cardio-pulmonary hemodynamics and disease severity in subjects with PH after LVAD implantation.
To evaluate the safety and tolerability of macitentan 10 mg in subjects with PH after LVAD implantation.
Exploratory objectives To explore the potential effect of macitentan 10 mg as compared to placebo on right ventricular function in subjects with PH after LVAD implantation.
To explore the potential effect of macitentan 10 mg as compared to placebo on selected clinical events in subjects with PH after LVAD implantation.
To explore the potential effect of macitentan 10 mg as compared to placebo on renal function as measured by glomerular filtration rate (GFR) in subjects with PH after LVAD implantation.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pulmonary Hypertension | Drug: Macitentan 10mg Drug: Placebo sugar pill | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 57 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Prospective, Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of Macitentan in Patients With Pulmonary Hypertension After Left Ventricular Assist Device Implantation |
| Actual Study Start Date : | March 28, 2016 |
| Actual Primary Completion Date : | March 13, 2020 |
| Actual Study Completion Date : | March 13, 2020 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Macitentan 10 mg po
Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.
|
Drug: Macitentan 10mg
2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
Other Name: Active drug |
|
Placebo Comparator: Placebo sugar pill
Approximately 78 adult subjects with PH post-LVAD implantation will be randomized (1:1) to receive either macitentan 10 mg, or matching placebo, once daily orally.
|
Drug: Placebo sugar pill
2 groups, randomized in a 1:1 ratio by an Interactive Voice/Web Randomization System to macitentan 10 mg or placebo
Other Name: placebo comparator |
- Pulmonary Vascular Resistance (PVR) ratio of Week 12 to Baseline. [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in mean right atrial pressure (mPAP) [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in mean pulmonary arterial pressure (mPAP) [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in pulmonary arterial wedge pressure (PAWP) [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in cardiac index (CI) [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in total pulmonary resistance [ Time Frame: 12 weeks ]
- Change from Baseline to Week 12 in mixed venous oxygen saturation [ Time Frame: 12 weeks ]
- Change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) from Baseline to Week 12. [ Time Frame: 12 weeks ]
- Change in World Health Organization (WHO) functional class from Baseline to Week 12 [ Time Frame: 12 weeks ]
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Written Informed Consent prior to initiation of any study-mandated procedure.
- Males or females ≥ 18 years of age.
- Surgical implantation of LVAD within 90 days prior to Randomization.
-
Hemodynamic evidence of PH on Baseline right heart catheterization (RHC) by the thermodilution method. Baseline RHC is defined as the last hemodynamic measurements after LVAD implantation and prior to the first dose of study treatment. PH is defined as:
- Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and
- Pulmonary artery wedge pressure (PAWP) ≤ 18 mmHg and
- PVR > 3 Wood units.
-
Stabilization of the patient for 48 h prior to the Baseline RHC, defined as:
- No LVAD pump speed/flow rate changes and
- Stable dose of oral diuretics and
- No intravenous (i.v.) inotropes or vasopressors and
- Patient able to ambulate.
-
A woman of childbearing potential is eligible only if she has:
- A negative serum pregnancy test result during the Screening period (Visit 1) and Randomization (Visit 2) and
- Agreement to undertake monthly serum pregnancy tests during the study and up to 30 days after study treatment discontinuation and
- Agreement to use one of the methods of contraception / follow the contraception scheme described in Section 4.5 from Screening and up to at least 30 days after study treatment discontinuation.
- Patient must be randomized within 14 days of Baseline RHC.
Exclusion Criteria:
- Documented severe obstructive lung disease defined as: forced expiratory volume in 1 second / forced vital capacity (FEV1/FVC) < 0.7 associated with FEV1 < 50% of predicted value after bronchodilator administration.
- Documented moderate to severe restrictive lung disease defined as: total lung capacity < 60% of predicted value.
- Documented pulmonary veno-occlusive disease.
- Patients undergoing dialysis.
- Hemoglobin < 8.5 g/dL at Randomization.
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 × the upper limit of normal (ULN) at Randomization.
- Severe hepatic impairment, e.g., Child-Pugh Class C liver disease.
- Body weight < 40 kg at Randomization.
- Doppler mean blood pressure < 65 mmHg at Randomization.
- GFR < 30 mL/min at Randomization.
- Pregnant, planning to become pregnant during the study period, or breastfeeding.
- Treatment with endothelin receptor antagonists (ERAs), phosphodiesterase-5 (PDE5) inhibitors, i.v., subcutaneous (s.c.), or oral prostanoids, or guanylate cyclase stimulators within 7 days prior to Baseline RHC or study treatment initiation.
- Treatment with inhaled prostanoids (e.g., iloprost, epoprostenol) or nitric oxide within 24 h prior to Baseline RHC or study treatment initiation.
- Treatment with strong inducers of cytochrome P450 isozyme 3A4 (CYP3A4) within 28 days prior to study treatment initiation (e.g., carbamazepine, rifampicin, rifabutin, phenytoin and St. John's Wort).
- Treatment with strong inhibitors of CYP3A4 within 28 days prior to study treatment initiation (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, saquinavir, boceprevir, telaprevir, iopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, and idinavir).
- Treatment with another investigational drug (planned, or taken) within 28 days prior to study treatment initiation.
- Known hypersensitivity to ERAs, or to any of the study treatment excipients.
- Any condition that prevents compliance with the protocol or adherence to therapy.
- Known concomitant life-threatening disease with a life expectancy < 12 months.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02554903
Show 50 study locations
| Study Director: | Mark Rocco | Actelion |
| Responsible Party: | Actelion |
| ClinicalTrials.gov Identifier: | NCT02554903 |
| Other Study ID Numbers: |
AC-055-205 |
| First Posted: | September 18, 2015 Key Record Dates |
| Last Update Posted: | April 15, 2020 |
| Last Verified: | April 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
|
LVAD |
|
Hypertension, Pulmonary Hypertension Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases |
Macitentan Endothelin A Receptor Antagonists Endothelin Receptor Antagonists Molecular Mechanisms of Pharmacological Action Endothelin B Receptor Antagonists |