Pharmacotherapy for Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia: Past, Present, and Future
Abstract
:1. Introduction
2. General Management
3. Pharmacotherapy Targeting NO Signaling
3.1. Inhaled NO
3.2. Sildenafil
3.3. L-Citrulline
3.4. Tadalafil
3.5. Riociguat
4. Pharmacotherapy Targeting Non-NO Signaling Pathways
4.1. Endothelin-1 Signaling
4.2. Prostacyclin Signaling
5. Challenges for RCT Design in Patients with or at Risk of Developing BPD-PH
5.1. Therapeutic Goals
5.2. Eligibility Criteria
5.3. Therapeutic End-Points
5.3.1. Transthoracic Echocardiographic (TTE) End-Points
5.3.2. Respiratory End-Points
5.3.3. Long-Term End-Points
6. Additional Comments about RCTs Manipulating NO Signaling
7. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug Name | Signaling Pathway | Type of Studies Published for Use in BPD-PH | Clinical Trial Phase for Use in BPD-PH | FDA Approval |
---|---|---|---|---|
iNO | NO-cyclic GMP | Observational | No phase 1, 2, or 3 studies currently planned or ongoing for BPD-PH | Not approved for BPD-PH Approved for PPHN in term and near-term newborns |
Sildenafil | NO-cyclic GMP | Observational Phase 1 PK study in premature infants at risk of BPD NCT01670136 | Phase 2 study in infants at risk of BPD NCT03142568 Phase 2 study in infants with severe BPD NCT04447989 | Not approved for BPD-PH Approved for adults with PH |
L-citrulline | NO-cyclic GMP | Phase 1 PK study in premature infants at risk of BPD-PH NCT03542812 | Phase 1 PK and safety study in premature infants with severe BPD NCT05636397 | Not approved for BPD-PH Not approved for any age group of patients with PH |
Bosentan | Endothelin-1 | Observational | No phase 1, 2, or 3 studies currently planned or ongoing for BPD-PH | Not approved for BPD-PH Approved for adults and children > 3 yrs of age with PH |
Epoprostenol | Prostacyclin | Observational | No phase 1, 2, or 3 studies currently planned or ongoing for BPD-PH | Not approved for BPD-PH Approved for adults with PH |
Treprostinil | Prostacyclin | Observational | No phase 1, 2, or 3 studies currently planned or ongoing for BPD-PH | Not approved for BPD-PH Approved for adults with PH |
Iloprost | Prostacyclin | Observational | No phase 1, 2, or 3 studies currently planned or ongoing for BPD-PH | Not approved for BPD-PH Approved for adults with PH |
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Fike, C.D.; Aschner, J.L. Pharmacotherapy for Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia: Past, Present, and Future. Pharmaceuticals 2023, 16, 503. https://doi.org/10.3390/ph16040503
Fike CD, Aschner JL. Pharmacotherapy for Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia: Past, Present, and Future. Pharmaceuticals. 2023; 16(4):503. https://doi.org/10.3390/ph16040503
Chicago/Turabian StyleFike, Candice D., and Judy L. Aschner. 2023. "Pharmacotherapy for Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia: Past, Present, and Future" Pharmaceuticals 16, no. 4: 503. https://doi.org/10.3390/ph16040503