a long term study to find out if macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction and pulmonary vascular disease

Conditions: Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease

Summary: the aim of this open-label (ol) extension trial is to study the long-term safety and efficacy of macitentan in subjects with heart failure with preserved ejection fraction (hfpef) and pulmonary vascular disease (pvd) beyond the treatment in the double-blind parent serenade study (ac-055g202, nct03153111). furthermore, this ol extension study will give eligible subjects of the main study (serenade/ac-055g202, nct03153111) an opportunity to continue or start receiving macitentan.


Eligibility criteria:
inclusion criteria: * signed and dated informed consent form (icf). * participant remained in the main study (serenade/ac-055g202, nct03153111) for: a) 52 weeks after randomization if entered this open-label (ol) extension study prior to protocol version 4, b) at least 24 weeks after randomization if entering this ol extension study under protocol version 4 * a woman of childbearing potential is eligible only if: (1) negative pre-treatment serum pregnancy test; (2) agreement to undertake monthly pregnancy tests from the enrollment visit up to at least 30 days after study treatment discontinuation; and (2) agreement to use reliable contraception from at least 30 days prior to the enrollment visit up to at least 30 days after study treatment discontinuation. exclusion criteria: * premature discontinuation of study treatment in the main study (serenade/ac-055g202, nct03153111) due to an adverse event related to: (1) edema or fluid retention; (2) worsening of heart failure; (3) liver aminotransferase elevation; and (4) study treatment, based on investigators' discretion * liver aminotransferase elevations, at the enrollment visit, fulfilling the following criteria: (1) alanine amino transferase (alt) / aspartate aminotransferase (ast) greater than or equal to (\>=) 8 \* the upper limit of normal (uln); (2) alt/ast \>= 3 \* uln and associated clinical symptoms of liver injury, for example: nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue, flu-like syndrome (arthralgia, myalgia, fever); and (3) alt/ast \>= 3 \* uln and associated increase in total bilirubin to \>= 2 \* uln * treatment with the following forbidden medications within 1 month prior to the enrollment visit: (1) treatments that may interfere with the assessment of efficacy (that is, endothelin receptor antagonists, prostanoids, phosphodiesterase-5 inhibitors, guanylate cyclase stimulators); (2) strong cytochrome p-450 3a4 (cyp3a4) inducers such as rifabutin, rifampin, rifampicin, rifapentin, carbamazepine, phenobarbital, phenytoin, or st. john's wort; (3) strong cyp3a4 inhibitors such as ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir or a moderate dual cyp3a4/cyp2c9 inhibitor (for example, fluconazole or amiodarone) or co-administration of a combination of moderate cyp3a4 (for example, ciprofloxacin, cyclosporine, diltiazem, erythromycin, verapamil) and moderate cyp2c9 inhibitors (for example, miconazole, piperine), in the 1-month period prior to baseline. this will not necessarily apply to participants who are already well-managed on such an ongoing combination; and (4) any other investigational treatment * pregnant, planning to be become pregnant or lactating. * any known factor or disease that might interfere with treatment compliance, study conduct, or interpretation of the results, such as drug or alcohol dependence or psychiatric disease. * known hypersensitivity to macitentan or drugs of the same class, or any of the study drug excipients (for example, soy lecithin, lactose)

Keywords: pulmonary vascular disease macitentan heart failure with preserved ejection fraction