Table 2.
Main characteristics of the selected RCT (status as at 30 April 2023)
| Novel therapies | Drugs | Clinical trials | Study duration | Main outcomes | Current status |
|---|---|---|---|---|---|
| Bone morphogenetic protein receptor type 2 (BMPR2) signaling and activating receptor type IIA/B | Sotatercept | HYPERION NCT04811092 (phase III, 662 estimated participants) | 24 weeks | Time to clinical worsening | Recruiting |
| SOTERIA NCT04796337 (phase III, 700 estimated participants) | 200 weeks | AEs | Recruiting | ||
| ZENITH NCT04896008 (phase III, 200 estimated participants) | 46 months | Time to first confirmed morbidity or mortality event | Recruiting | ||
| Prostacyclin receptor agonists | Ralinepag | ROR-PH-301 ADVANCE OUTCOMES NCT03626688 (phase III, 1000 estimated participants) | 42 months | Time to clinical events | Recruiting |
| ROR-PH-302 ADVANCE CAPACITY3 NCT04084678 (phase III, 193 estimated participants) | 28 weeks | VO2 consumption at week 28 | Active | ||
| ROR-PH-303, ADVANCE EXTENSION NCT03683186 (phase III, 1000 estimated participants) | 6 years | AEs | Enrolling by invitation | ||
| Treprostinil | NCT04791514 (phase II, 1 participant) | 30 days | Number of participants who experience a TEAE | Terminated in August 2022 | |
| NCT05147805 (phase II, 99 estimated participants) | 3 weeks | PVR | Recruiting | ||
| L606 | NCT04691154 (phase III, 60 estimated participants) | 12 months | Short-term safety and tolerability, steady-state pharmacokinetics, 6MWD, QoL and treatment satisfaction | Recruiting | |
| Serotonin (5-HT) signaling pathway | Rodatristat ethyl | ELEVATE 2 NCT04712669 (phase IIb, 90 estimated participants) | 24 weeks | PVR | Recruiting |
| Vasoactive intestinal peptide (VIP) pathway | Pemziviptadil | NCT03556020 (phase II, 35 estimated participants) | 6 weeks | PVR | Terminated in January 2022 |
| NCT03795428 (phase II, 25 estimated participants) | 28 days after last dose | AEs and long-term tolerability profile | Terminated in January 2022 | ||
| Soluble guanylate cyclase stimulators | MK-5475 | INSIGNIA-PAH NCT04732221 (phase II/phase III, 450 estimated participants) | 12 weeks and 24 months | PVR and 6MWD | Recruiting |
| Kinase inhibitors | Imatinib | NCT04416750 (phase II, 43 estimated participants) | 12 months and 24 months | Highest tolerated dose of imatinib and PVR | Recruiting |
| IMPAHCT NCT05036135 (phase IIb/III, 422 estimated participants) | 24 weeks | PVR, 6MWD | Recruiting | ||
| IMPAHCT-FUL NCT05557942 (phase III, 462 estimated participants) | 48 weeks | Incidence of adverse events | Recruiting | ||
| Seralutinib | NCT04816604 (phase II, 100 estimated participants) | 148 weeks | AEs | Recruiting | |
| Estrogen receptor modulators | Tamoxifen | T3PAH NCT03528902 (phase II, 24 estimated participants) | 24 weeks | ECHO-based change in the TAPSE measurement | Recruiting |
| Phosphodiesterase-5 inhibitors | TPN171H (simmerafil) | NCT04483115 (phase IIa, 60 participants) | 24 hours after drug administration | PVR, time of maximum change in the AUC, change in arterial oxygenation and change in right ventricular function | Recruiting |
| Vardenafil | VIPAH-PRN 2B NCT04266197 (phase IIb, 86 participants) | From baseline to follow-up day 15 post-treatment | AEs, change in vital signs, VO2 | Recruiting | |
| Aberrant epigenetic changes | CS1 | NCT05224531 (phase II, 30 estimated participants) | 6 months | AEs | Recruiting |
| Block IL-6 receptor | Satralizumab | SATISFY-JP, NCT05679570 (phase II, 24 estimated participants) | 24 weeks | PVR | Recruiting |
| Smurf-1 inhibitor | LTP001 | NCT05135000 (phase II, 44 estimated participants) | 24 weeks | PVR | Recruiting |
6MWD 6-minute walk distance, AEs adverse events, AUC area under the curve, ECHO transthoracic echocardiogram, PVR pulmonary vascular resistance, QoL quality of life, RCT randomized controlled trial, TAPSE tricuspid annular plane systolic excursion, TEAE treatment emergent adverse event, VO2 peak oxygen uptake