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Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial
BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of B...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer International Publishing
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800408/ https://www.ncbi.nlm.nih.gov/pubmed/31414269 http://dx.doi.org/10.1007/s40261-019-00834-0 |
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author | Abounahia, Fouad F. Abu-Jarir, Rawia Abounahia, Mohamed F. Al-Badriyeh, Daoud Abushanab, Dina Abu-Ghalwa, Mahmoud Mansour, Ashraf Kurdi, Bader Al-Rifai, Hilal |
author_facet | Abounahia, Fouad F. Abu-Jarir, Rawia Abounahia, Mohamed F. Al-Badriyeh, Daoud Abushanab, Dina Abu-Ghalwa, Mahmoud Mansour, Ashraf Kurdi, Bader Al-Rifai, Hilal |
author_sort | Abounahia, Fouad F. |
collection | PubMed |
description | BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. OBJECTIVE: To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. METHODS: This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women’s Wellness and Research Center, Doha, Qatar during 2012–2014. Infants of 24(0/7)–29(6/7) weeks’ gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. RESULTS: No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. CONCLUSIONS: While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD. |
format | Online Article Text |
id | pubmed-6800408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-68004082019-11-01 Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial Abounahia, Fouad F. Abu-Jarir, Rawia Abounahia, Mohamed F. Al-Badriyeh, Daoud Abushanab, Dina Abu-Ghalwa, Mahmoud Mansour, Ashraf Kurdi, Bader Al-Rifai, Hilal Clin Drug Investig Original Research Article BACKGROUND: Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. OBJECTIVE: To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. METHODS: This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women’s Wellness and Research Center, Doha, Qatar during 2012–2014. Infants of 24(0/7)–29(6/7) weeks’ gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. RESULTS: No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. CONCLUSIONS: While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD. Springer International Publishing 2019-08-14 2019 /pmc/articles/PMC6800408/ /pubmed/31414269 http://dx.doi.org/10.1007/s40261-019-00834-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Original Research Article Abounahia, Fouad F. Abu-Jarir, Rawia Abounahia, Mohamed F. Al-Badriyeh, Daoud Abushanab, Dina Abu-Ghalwa, Mahmoud Mansour, Ashraf Kurdi, Bader Al-Rifai, Hilal Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title | Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title_full | Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title_fullStr | Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title_full_unstemmed | Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title_short | Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial |
title_sort | prophylactic sildenafil in preterm infants at risk of bronchopulmonary dysplasia: a pilot randomized, double-blinded, placebo-controlled trial |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800408/ https://www.ncbi.nlm.nih.gov/pubmed/31414269 http://dx.doi.org/10.1007/s40261-019-00834-0 |
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