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

United Therapeutics

Status and phase: Terminated; Phase 2

Conditions: Persistent Pulmonary Hypertension of the Newborn

Treatments: Drug: IV Remodulin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02261883

RIV-PN-201

Details and patient eligibility

About

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).

Full 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).

Enrollment: 42 patients

Sex: All

Ages: 1 hour to 14 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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42 participants in 2 patient groups, including a placebo group

IV Remodulin

Active Comparator group

Description:

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.

Treatment:

Drug: IV Remodulin

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo