Opsumit (macitentan) / Nippon Shinyaku, J&J - LARVOL DELTA

Transient early increase in echocardiographically estimated pulmonary artery pressure after closure of a large patent ductus arteriosus in an adult: a case report. (PubMed, Front Med (Lausanne)) - "Diuretics and macitentan were administered during the postoperative period; however, the relative contributions of medical therapy, changes in volume status, postoperative cardiovascular adaptation, and spontaneous recovery cannot be determined from this single case. Because postoperative invasive hemodynamic reassessment was unavailable, the mechanism underlying the transient increase in estimated SPAP remains uncertain. This case illustrates that a marked early rise in echocardiographically estimated SPAP after PDA closure may be transient and should be interpreted in conjunction with serial echocardiographic findings, clinical status, and available hemodynamic data."

Journal • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

EPIPHANY: Effects of Combination Medical Therapy Followed by BPA on Right Ventricular-PA Coupling and Hemodynamics in CTEPH (clinicaltrials.gov) - P3 | N=7 | Terminated | Sponsor: Dr Sudarshan Rajagopal | N=15 ➔ 7 | Trial completion date: Dec 2026 ➔ May 2026 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2026 ➔ Mar 2026; Sponsor Requested

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases

Simultaneous Liver-Kidney Transplantation in the Setting of Severe Port-Pulmonary Hypertension (ACG 2026) - "She was on tadalafil 40 mg daily and inhaled treprostinil 80 mcg; prior trials of selexipag and macitentan were discontinued due to intolerance and worsening anemia, respectively. Sotatercept was contraindicated given thrombocytopenia...Despite intolerance or contraindication to several standard pulmonary vasodilators, the patient was bridged to transplant with intravenous treprostinil, renal replacement therapy and careful volume management, to meet hemodynamic listing criteria. This case illustrates the importance of individualized, dynamic risk assessment in PoPH patients."

Cardiovascular • Fibrosis • Genetic Disorders • Hematological Disorders • Hepatology • Immunology • Nephrology • Polycystic Kidney Disease • Portal Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Thrombocytopenia • Thrombosis • Transplantation

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Jul 2029 ➔ Sep 2030

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Pulmonary Arterial Hypertension With Moyamoya Disease Harboring the RNF213 p.Arg4810Lys Variant Presenting a Favorable Response to Monotherapy: A Case Report. (PubMed, Pulm Circ) - "We initiated endothelin receptor antagonist (macitentan, 10 mg/day) monotherapy because upfront combination therapy may also cause hypotension...The clinical spectrum of RNF213-associated PAH may be broader than previously reported. This case highlights the importance of personalized medicine that considers patient conditions and comorbidities when selecting treatment options for patients with PAH harboring the RNF213 p.Arg4810Lys variant."

Journal • Monotherapy • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Vascular Neurology

Improved cardiac function and quality of life with initial macitentan-tadalafil combination therapy compared to tadalafil alone in pulmonary arterial hypertension. (PubMed, Am J Transl Res) - "Initial combination therapy with macitentan and tadalafil provides superior hemodynamic, functional, and QOL benefits compared to tadalafil monotherapy in patients with PAH."

HEOR • Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Pulmonary Veno-Occlusive Disease Presenting as Congenital Heart Disease-Associated Pulmonary Hypertension. (PubMed, JACC Case Rep) - "PVOD should be considered in children with CHD developing progressive pulmonary hypertension despite favorable hemodynamics and preserved vasoreactivity. The absence of pulmonary edema during vasodilator therapy does not exclude PVOD."

Journal • Cardiovascular • Heart Failure • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • Transplantation

Lung epithelial endothelin-1 drives iron dysregulation and skeletal injury after SARS-CoV-2 infection. (PubMed, Cell Rep) - "Therapeutically, the FDA-approved endothelin receptor antagonist, macitentan, protected infected hamsters from joint damage by reducing iron overload-associated chondrocyte dropout in both acute and subacute phase of infection in vivo. Our findings reveal the pathological ET-1 in lung-joint axis and highlight its receptors as therapeutic target for post-COVID skeletal sequelae."

Journal • Hematological Disorders • Infectious Disease • Musculoskeletal Diseases • Novel Coronavirus Disease • Respiratory Diseases • EDN1

Efficacy, Safety, and Pharmacokinetics of Macitentan in Japanese Pediatric Patients With Pulmonary Arterial Hypertension: Prospective, Multicenter, Open-Label Study. (PubMed, Circ Rep) - "Most adverse events were mild to moderate in severity, and none were considered related to macitentan. Macitentan showed clinically meaningful reduction in PVRI and improved pulmonary hemodynamics in Japanese pediatric patients with PAH, with a favorable safety profile over 52 weeks of treatment."

Journal • PK/PD data • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • Pediatrics • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Comparative clinical evaluation of endothelin receptor antagonists in pulmonary arterial hypertension using a multi-criteria decision analysis framework. (PubMed, Int J Clin Pharm) - "Within the proposed MCDA framework, ambrisentan achieved the highest overall score across multiple clinical and practical dimensions. The framework provides a transparent tool for structured evaluation, although economic and accessibility findings should be interpreted within the Chinese healthcare context."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Next-generation therapeutics and renaissance of legacy drugs targeting the endothelin system. (PubMed, Can J Physiol Pharmacol) - "Endothelin-1 (ET-1) was discovered in 1988, followed by identification of ETA and ETB receptors in 1990, enabling rapid development of the first endothelin receptor antagonists (bosentan, ambrisentan, and macitentan) for pulmonary arterial hypertension, a condition marked by elevated ET-1. Nearly a decade later, a new therapeutic wave began with the ETB agonist sovateltide (2021) for cerebral ischemic stroke, demonstrating the benefits of ETB activation...Clazosentan (ETA) for cerebral vasospasm and aprocitentan (ETA/ETB) for resistant hypertension extended endothelin-targeted therapy into more common diseases. In kidney disease, sparsentan (AT1/ETA) and atrasentan (ETA) have both been approved for IgA nephropathy, with atrasentan succeeding after earlier failed trials...This review outlines approaches for identifying legacy endothelin compounds suitable for new indications, using zibotentan, now combined with dapagliflozin to reduce fluid retention as an example. Kidney..."

Journal • Review • Cardiovascular • Glomerulonephritis • Hypertension • IgA Nephropathy • Ischemic stroke • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Renal Disease • Respiratory Diseases • EDN1

Sequential Add-On Therapy Modifies Mortality Risk Stratification in Group 1.4 Pulmonary Arterial Hypertension: A Real-World, Single-Center Retrospective Cohort Study from Mexico. (PubMed, J Clin Med) - "This study evaluated changes in risk classification using COMPERA 2.0 and REVEAL Lite 2 scores in patients treated with endothelin receptor antagonist (ERA) and phosphodiesterase type 5 inhibitor (PDE5i) combination therapy (macitentan + sildenafil) at a referral center in Mexico. Sequential add-on ERA + PDE5i therapy was associated with meaningful improvement in risk stratification among patients with Group 1.4 PAH. These findings support the clinical utility of simplified, noninvasive risk assessment tools in real-world settings, particularly in resource-constrained environments."

Journal • Real-world evidence • Retrospective data • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

UNISUS: Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3; N=900; Not yet recruiting; Sponsor: Actelion

Clinical • New P3 trial • Hypertension • Pulmonary Arterial Hypertension

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=252 | Recruiting | Sponsor: Actelion | Not yet recruiting ➔ Recruiting

Enrollment open • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

UNISUS: Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3 | N=935 | Active, not recruiting | Sponsor: Actelion | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3; N=252; Not yet recruiting; Sponsor: Actelion

Clinical • New P3 trial • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

UNISUS: Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3 | N=900 | Recruiting | Sponsor: Actelion | Trial completion date: Sep 2026 ➔ Feb 2029

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

UNISUS: Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3; N=900; Recruiting; Sponsor: Actelion; Not yet recruiting ➔ Recruiting; Trial completion date: Mar 2026 ➔ Aug 2026

Clinical • Enrollment open • Trial completion date • Hypertension • Pulmonary Arterial Hypertension

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Feb 2028 ➔ Sep 2029

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=230 | Recruiting | Sponsor: Actelion | Trial completion date: Jan 2027 ➔ May 2027

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Mar 2029 ➔ Sep 2030

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

UNISUS: Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension (clinicaltrials.gov) - P3 | N=900 | Recruiting | Sponsor: Actelion | Trial primary completion date: Oct 2023 ➔ Aug 2025

Trial primary completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=230 | Recruiting | Sponsor: Actelion | Trial completion date: May 2027 ➔ Feb 2028

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Sep 2029 ➔ Feb 2028

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

PLATYPUS: A Study Providing Treatment Access in Participants With Pulmonary Hypertension Completing a Parent Study and Having no Other Option (clinicaltrials.gov) - P3 | N=280 | Recruiting | Sponsor: Actelion | Trial completion date: Feb 2028 ➔ Mar 2029

Trial completion date • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases