Population Pharmacokinetics and Dosage Individualization of Oral Pulmonary Vasodilators in PPHN

Population Pharmacokinetics and Dosage Individualization of Bosentan, Sildenafil and Tadalafil in Persistent Pulmonary Hypertension of the Newborn

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Persistent Pulmonary Hypertension of the Newborn
• Intervention / Treatment: Drug: Bosentan Tablets; Drug: Sildenafil Tablet; Drug: Tadalafil Tablets

• Study Type: Observational
• Enrollment (Anticipated): 500

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Second University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Neonates suffered from persistent pulmonary hypertension

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Treatment(bosentan, sildenafil and tadalafil)	Drug: Bosentan Tablets; 2mg/kg, bid; Drug: Sildenafil Tablet; 1mg/kg, q6h/q8h; Drug: Tadalafil Tablets; 1mg/kg, qd

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Shandong University
• Collaborators: West China Second University Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 26, 2020
• Primary Completion (ANTICIPATED): February 26, 2023
• Study Completion (ANTICIPATED): May 30, 2023

Study Registration Dates

• First Submitted: April 26, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (ACTUAL): May 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 7, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Hypertension; Hypertension, Pulmonary; Persistent Fetal Circulation Syndrome; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Endothelin Receptor Antagonists; Sildenafil Citrate; Tadalafil; Bosentan
• Other Study ID Numbers: 2020_PPHN_001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No