Children's National

Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn

Purpose

This study assessed the safety and treatment effect of intravenous (IV) Remodulin as an add-on therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN).

Condition

Persistent Pulmonary Hypertension of the Newborn

Eligibility

Eligible Ages: Between 1 Hour and 14 Days
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Parent(s) or legal guardian provided consent for the subject to participate - Weight at least 2 kg at Screening - Gestational age of ≥34 weeks and ≤14 days old at Screening - Diagnosis of PPHN, which was either idiopathic in nature or associated with the following: meconium aspiration syndrome, pneumonia, respiratory distress syndrome, sepsis, birth hypoxia, perinatal encephalopathy, or unilateral congenital diaphragmatic hernia - Currently requiring ventilator support - Two consecutive oxygenation index (OI) of 15 or greater separated by at least 30 minutes, after receiving iNO for at least 3 hours - Echocardiographic (ECHO) evidence of pulmonary hypertension with elevated right ventricle pressure - Dedicated venous access for the administration of study drug (central line or peripherally inserted central venous catheter)

Exclusion Criteria

Previous or concurrent use of a phosphodiesterase-5 inhibitor, endothelin receptor antagonist, or prostanoid - Significant congenital heart disease as detected by ECHO, minor valvular abnormalities, or expected transitional findings such as a patent foramen ovale, or patent ductus arteriosus. - Clinically significant, untreated active pneumothorax at Screening - Evidence of clinically significant bleeding at Screening - Necrotizing enterocolitis (≥Bells stage II at Screening) - Uncontrolled hypotension (mean systemic pressures ≤35 mmHg at Screening) - Uncontrolled coagulopathy and / or untreated thrombocytopenia (<50,000 platelets/µL at Screening) - History of severe (Grade 3 or 4) intracranial hemorrhage at Screening - Currently receiving extracorporeal mechanical oxygenation (ECMO) or had immediate plans to initiate ECMO - Expected duration on mechanical ventilation of <48 hours - Life expectancy was less than 2 months or had a lethal chromosomal anomaly - Contraindication to ECMO - Bilateral congenital diaphragmatic hernia - Active seizures at Screening - Currently participating in another clinical drug study

Study Design

Phase: Phase 2
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

Arm	Description	Assigned Intervention
Active Comparator IV Remodulin	The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose.	Drug: IV Remodulin Treprostinil is a chemically stable tricyclic analogue of prostacyclin. Other names: Treprostinil
Placebo Comparator Placebo	The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose.	Drug: Placebo Sodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous).

Recruiting Locations

More Details

NCT ID: NCT02261883
Status: Terminated
Sponsor: United Therapeutics

Detailed Description

This study was designed to investigate if the addition of Remodulin reduced the rate of clinical worsening (defined as the need for additional treatment targeting PPHN, need for extracorporeal mechanical oxygenation [ECMO], or death) in neonatal subjects with PPHN who did not show an adequate response to inhaled nitric oxide (iNO). This study was part of a pediatric investigation plan agreed upon by the EMA (EMEA 000207-PIP01-08-M08).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.