TABLE 2.
Clinical trials and selected retrospective studies targeting COPD, interstitial lung disease (ILD) and ILD-pulmonary hypertension (PH) with PH medications#
| First author, year [reference] | Lung disease | Study design | Subjects n | Therapy | Results | Comments |
|---|---|---|---|---|---|---|
| COPD trials | ||||||
| Vitulo, 2017 [167] | COPD-PH | RCT | 28 | Sildenafil (n=18) | Decrease in PVR, improvement in BODE, DLCO and quality of life | No adverse effect on oxygenation |
| Maron, 2022 [168] | COPD-PH | RCT | 42 | Tadalafil (n=28) | No change in PVR or mPAP at 6 months Improvement in shortness-of-breath questionnaire |
No adverse effect on oxygenation |
| Nathan, 2024 [169] | COPD-PH | RCT | 136 | Inhaled treprostinil (n=66) | Decrease in 6MWD at 12 weeks | Study terminated due to increased SAE in the treated group |
| ILD/IIP/IPF trials | ||||||
| Kolb, 2018 [170] | IPF | RCT | 274 | Nintedanib+sildenafil (n=137) | Primary end-point of change in SGRQ was not met | |
| Behr, 2021 [171] | IPF | RCT | 177 | Pirfenidone+sildenafil (n=88) | No difference in disease progression (composite end-point) | Composite end-point of decline in 6MWD and hospitalisation or all-cause mortality |
| Nathan, 2020 [ 172] | Fibrotic ILD |
RCT | 45 | iNO (n=23) | Improvement in moderate to vigorous and overall activity | Patients on supplemental oxygen |
| Bellerophon Pulse Technologies [173] | Fibrotic ILD |
RCT | 145 | iNO (n=73) | Did not improve moderate to vigorous activity | Patients on supplemental oxygen |
| PH associated with ILD/IIP/IPF trials | ||||||
| Faria-Urbina, 2018 [174] | ILD-PH | Retrospective | 22 | Treprostinil (inhaled) (n=22) |
Improvement in FC and 6MWD No change in resting oxygen requirements |
|
| Nathan, 2019 [62] | IIP-PH | RCT | 147 | Riociguat (n=73) | Terminated early for unfavourable risk/benefit profile | Post hoc analysis of CT scans suggested that advanced CPFE phenotype with emphysema >> fibrosis may have contributed to the negative signal [87] |
| Waxman, 2021 [61] | ILD-PH | RCT | 326 | Treprostinil (inhaled) (n=163) |
Improved 6MWD, NT-proBNP, clinical worsening and FVC | |
| Dawes, 2023 [175] | ILD-PH | Retrospective | 60 | PDE-5i (n=50) ERAs (n=10) |
Patients treated with sildenafil showed longer survival | No effect on V′/Q′ matching |
IIP: idiopathic interstitial pneumonia; IPF: idiopathic pulmonary fibrosis; RCT: randomised controlled trial; PVR: pulmonary vascular resistance; BODE: body mass index, airflow obstruction, dyspnoea and exercise capacity; DLCO: diffusion capacity of the lung for carbon monoxide; mPAP: mean pulmonary artery pressure; 6MWD: 6-min walk distance; SAE: serious adverse effects; SGRQ: St George's Respiratory Questionnaire; iNO: inhaled nitric oxide; FC: functional class; CT: computed tomography; CPFE: combined pulmonary fibrosis emphysema; NT-proBNP: N-terminal pro-brain natriuretic peptide; FVC: forced vital capacity; PDE-5i: phosphodiesterase-5 inhibitor; ERA: endothelin receptor antagonist; V′/Q′: ventilation/perfusion ratio. #: published after the 6th World Symposium on Pulmonary Hypertension.