Bosentan as Adjunctive Therapy for Persistent Pulmonary Hypertension of the Newborn: Results of the Randomized Multicenter Placebo-Controlled Exploratory Trial.

Details

Serval ID
serval:BIB_D6F62198A0D0
Type
Article: article from journal or magazin.
Publication sub-type
Editorial
Collection
Publications
Institution
Title
Bosentan as Adjunctive Therapy for Persistent Pulmonary Hypertension of the Newborn: Results of the Randomized Multicenter Placebo-Controlled Exploratory Trial.
Journal
The Journal of pediatrics
Author(s)
Steinhorn R.H., Fineman J., Kusic-Pajic A., Cornelisse P., Gehin M., Nowbakht P., Pierce C.M., Beghetti M.
Working group(s)
FUTURE-4 study investigators
ISSN
1097-6833 (Electronic)
ISSN-L
0022-3476
Publication state
Published
Issued date
10/2016
Peer-reviewed
Oui
Volume
177
Pages
90-96.e3
Language
english
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
Publication Status: ppublish
Abstract
To evaluate the efficacy, safety, and pharmacokinetics of the endothelin receptor antagonist bosentan as adjunctive therapy for neonates with persistent pulmonary hypertension of the newborn (PPHN).
This was a phase 3, multicenter, randomized, placebo-controlled exploratory trial (FUTURE-4). Eligible patients were >34 weeks gestation, <7 days old, receiving inhaled nitric oxide (iNO) treatment (≥4 hours), and had persistent respiratory failure (oxygenation index [OI] ≥12). After 2:1 randomization, bosentan 2 mg/kg or placebo was given by nasogastric tube twice daily for ≥48 hours and up to 1 day after iNO weaning.
Twenty-one neonates received a study drug (13 bosentan, 8 placebo). Compared with the placebo group, the group treated with bosentan had a higher median baseline OI and greater need for vasoactive agents. One treatment failure (need for extracorporeal membrane oxygenation) occurred in the group treated with bosentan. The time to weaning from iNO or mechanical ventilation was not different between the groups. Bosentan was well tolerated and did not adversely affect systemic blood pressure or hepatic transaminase levels. Anemia and edema were more frequent in patients receiving bosentan. Blood concentrations of bosentan were low and variable on day 1, and achieved steady state on day 5.
Adjunctive bosentan was well tolerated, but did not improve oxygenation or other outcomes in our patients with PPHN. This effect may be related to delayed absorption of bosentan on treatment initiation in critically ill neonates or to more severe illness of the neonates who received bosentan.
ClinicalTrials.gov:NCT01389856.
Keywords
Bosentan, Double-Blind Method, Endothelin Receptor Antagonists/adverse effects, Endothelin Receptor Antagonists/therapeutic use, Female, Humans, Infant, Newborn, Male, Nitric Oxide/administration & dosage, Persistent Fetal Circulation Syndrome/drug therapy, Respiration, Artificial, Sulfonamides/adverse effects, Sulfonamides/therapeutic use, Treatment Failure, Treatment Outcome, endothelin, hypertension, pediatrics, pharmacology, pulmonary
Pubmed
Web of science
Create date
10/01/2019 16:49
Last modification date
11/10/2019 5:26
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