El-Hindi S. Vardenafil efficacy for the treatment of persistent pulmonary hypertension of the newborn. World J Clin Pediatr 2026; 15(3): 118862 [DOI: 10.5409/wjcp.118862]
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El-Hindi S. Vardenafil efficacy for the treatment of persistent pulmonary hypertension of the newborn. World J Clin Pediatr 2026; 15(3): 118862 [DOI: 10.5409/wjcp.118862]
Author contributions: El-Hindi S had primary responsibility for protocol development, patient screening, enrollment, outcome assessment, preliminary data analysis and writing the manuscript.
Institutional review board statement: The research was approved by the Ethical Review Board of Damascus University in January 2023 (No. MD 116/1800).
Clinical trial registration statement: The research was approved by the scientific research board of Damascus University in April 2023. Also registered on clinical trials registry. Clinicaltrials.gov identifier: NCT06860399.
Informed consent statement: Written informed consent was obtained from guardians prior to treatment initiation for participation and publication of the data.
Conflict-of-interest statement: No competing interests to disclose.
CONSORT 2010 statement: The author has read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Data sharing statement: Data sets analyzed in this study are not publicly available, but can be shared with researchers upon a reasonable request.
Received: January 13, 2026 Revised: February 13, 2026 Accepted: April 3, 2026 Published online: September 9, 2026 Processing time: 199 Days and 21.7 Hours
Abstract
BACKGROUND
Persistent pulmonary hypertension of the newborn (PPHN) remains a challenging condition with high morbidity and mortality despite advancements in management, which implies the need to investigate new therapies. While sildenafil is the drug of choice in resource-limited centers and for patients unresponsive to inhaled nitric oxide, alternative phosphodiesterase-5 inhibitors like vardenafil may offer superior efficacy.
AIM
To assess the efficacy of vardenafil in the management of persistent pulmonary hypertension in newborns.
METHODS
This randomized, double-blind, controlled, parallel clinical trial was conducted at Children’s Hospital, Damascus University. Fifty-five newborns (32 females and 23 males, < 96 hours old) with moderate to severe PPHN were allocated at a 1:2 ratio to receive 2 mg/kg/day oral sildenafil (n = 18) or 0.4 mg/kg/day oral vardenafil (n = 37). Recruitment lasted from May 2023 until September 2024. Clinical and echocardiographic findings were monitored daily from diagnosis until pulmonary pressure normalization.
RESULTS
The vardenafil group showed more rapid improvement. Pulmonary hypertension decreased significantly in the vardenafil group after 1 and 2 days (P = 0.002 and P < 0.001 respectively). Similarly, pulmonary vascular resistance decreased significantly in the vardenafil group after 1 day and 2 days (P = 0.001 and P = 0.015 respectively). Additionally, pulmonary artery flow velocity increased more in the vardenafil group after 1 day and 2 days (P = 0.046 and P = 0.048 respectively) and respiratory distress scores improved more in the vardenafil group after 2 days and 3 days of treatment (P = 0.048 and P = 0.004 respectively). No adverse events were reported in either treatment group.
CONCLUSION
Vardenafil at 0.4 mg/kg/day has superior efficacy compared with sildenafil at 2 mg/kg/day in improving echocardiographic and clinical outcomes in patients with PPHN, with comparable safety profiles. These findings suggest vardenafil may be a valuable option for PPHN management.
Core Tip: This is the first randomized controlled trial to evaluate the efficacy of vardenafil in the management of patients with persistent pulmonary hypertension of the newborn (PPHN). The study demonstrated that improvements in pulmonary hypertension, pulmonary vascular resistance, pulmonary artery flow velocity, and respiratory distress were faster in the vardenafil group than in sildenafil group without adverse events. These findings if confirmed in larger clinical trials may position vardenafil as a preferred first-line therapy for PPHN particularly in resource limited settings.
