Clinical trials with drugs targeting other signalling pathways

Drug identifierStudy designStudy durationMain inclusion criteriaPrimary outcome measuresSecondary outcome measures
Modulation of the oestrogen pathway: anastrozole and fulvestrant
 AnastrozoleNCT03229499RCT versus placebo: phase 2 (PHANTOM)24 weeksPAH in WHO FC I–III; stable PAH-specific therapy allowedChange in 6MWDChange in 6MWD (3 and 12 months), RVEF, NT-proBNP, biomarkers, SF-36, emPHasis-10, physical activity (actigraphy), TTCW and bone mineral density
 AnastrozoleNCT01545336Double-blind RCT versus placebo: phase 212 weeksPAH in WHO FC I–III on stable PAH-specific therapyChange in plasma oestradiol and in TAPSEChange in 6MWD
 FulvestrantNCT02911844Open-label: phase 29 weeksPost-menopausal female patients with PAH in WHO FC I–III on stable PAH-specific therapyChange in plasma oestradiol, TAPSE, 6MWD and NT-proBNP
Improvement of oxygenation: acetazolamide
 AcetazolamideNCT02755298Double-blind crossover RCT versus placebo: phase 2 and 35 weeksStable patients with pre-capillary PH who are undergoing RHC for a clinical indicationChange in 6MWDChange in QoL (MLHFQ), maximal ramp CPET, cerebral and muscle tissue oxygenation, daily activity (actigraphy), echocardiography parameters, FC, PRO (SF-36, CAMPHOR), NT-proBNP, etc.

RCT: randomised controlled trial; PAH: pulmonary arterial hypertension; WHO: World Health Organization; FC: functional class; 6MWD: 6-min walk distance; RVEF: right ventricular ejection fraction; NT-proBNP: N-terminal pro-brain natriuretic peptide; SF-36: Short Form-36; emPHasis-10: 10-question survey proposed by the Pulmonary Hypertension Association UK; TTCW: time to clinical worsening; TAPSE: tricuspid annular plane systolic excursion; PH: pulmonary hypertension; RHC: right heart catheterisation; QoL: quality of life; MLHFQ: Minnesota Living with Heart Failure Questionnaire; CPET: cardiopulmonary exercise testing; PRO: patient-reported outcome; CAMPHOR: Cambridge Pulmonary Hypertension Outcome Review.