Population Pharmacokinetics and Dosage Individualization of Oral Pulmonary Vasodilators in PPHN

• Conditions: Persistent Pulmonary Hypertension of the Newborn
• Interventions: Drug: Bosentan Tablets; Drug: Sildenafil Tablet; Drug: Tadalafil Tablets

• Registration Number: NCT04379180
• Lead Sponsor: Shandong University

Brief Summary

The use of bosentan, sildenafil and tadalafil in neonates with persistent pulmonary hypertension (PPHN) depends mostly on the empirical experience of pediatricians. Moreover, the recommended dose of those three drugs in treating PPHN remains controversial. Therefore, our aim is to study the pharmacokinetics and pharmacodynamics of bosentan, sildenafil and tadalafil in neonates of PPHN then dose a tailor-made therapeutic regimen.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-04-26
• Study First Submitted: 2020-04-26
• Status Verified: 2020-05
• Study First Submitted QC: 2020-05-06
• Last Update Submitted: 2020-05-06
• Study First Posted: 2020-05-07
• Last Update Posted: 2020-05-07
• Primary Completion: 2023-02-26
• Study Completion: 2023-05-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

Inclusion Criteria

• Age: postnatal age ≤ 28 days;
• Patients have been diagnosed with PPHN;
• Bosentan, sildenafil and/or tadalafil used as part of regular treatment.
• Parental written consent

Exclusion Criteria

• Expected survival time less than the treatment cycle;
• Major congenital malformations;
• Undergoing surgery within the first week of life;
• Receiving other systemic trial drug therapy;
• Other factors that the researcher considers unsuitable for inclusion.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Treatment(bosentan, sildenafil and tadalafil)	Bosentan Tablets	-
Treatment(bosentan, sildenafil and tadalafil)	Tadalafil Tablets	-
Treatment(bosentan, sildenafil and tadalafil)	Sildenafil Tablet	-

Primary Outcome Measures

Name	Time	Method
The change of hemodynamics	Through study completion, an average of 5 days	* Pulmonary artery pressure (mmHg); * Alveolar-arterial gradient (mmHg)
Oxygenation index	The first 72 hours of the initial treatment	Oxygenation index=(fraction of inspired oxygen\*mean airway pressure)/the partial pressure of arterial oxygen

Secondary Outcome Measures

Name	Time	Method
Sequelae of PPHN	Through study completion and a 6-month visit	Including cerebral palsy, hearing impairment, neurodevelopmental outcome etc
Pulse oxygen saturation	The first 72 hours of the initial treatment	Pulse oxygen saturation（%）
Duration of hospitalization	Within the first 28 days of patients' life	Duration of initial therapy
Death	Within the first 28 days of patients' life	Death in the first 28 days of life
Adverse events	Through study completion, an average of 5 days	Drug-related adverse events and serious adverse events
The need of extra support	Through study completion, an average of 5 days	Besides the initial therapy (bosentan, sildenafil and/or tadalafil), other support such as inhaled nitric oxide (iNO), inotropic agents or Extracorporeal Membrane Oxygenation (ECMO)

Trial Locations

Locations (1)

West China Second University Hospital; 🇨🇳 Chengdu, Sichuan, China