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

NCT ID: NCT02261883

Last Updated: 2024-03-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-29
• Study Completion Date: 2023-05-17

Brief Summary

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).

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).

Conditions

Persistent Pulmonary Hypertension of the Newborn

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

IV Remodulin

Intervention Type: DRUG

Treprostinil is a chemically stable tricyclic analogue of prostacyclin.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous).

Interventions

IV Remodulin

Treprostinil is a chemically stable tricyclic analogue of prostacyclin.

Intervention Type: DRUG

Placebo

Sodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous).

Intervention Type: DRUG

Other Intervention Names

Treprostinil

Eligibility Criteria

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

• Minimum Eligible Age: 1 Hour
• Maximum Eligible Age: 14 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

United Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Children's Hospital of Los Angeles

Los Angeles, California, United States

Stanford Children's Hospital

Palo Alto, California, United States

All Children's Hospital

St. Petersburg, Florida, United States

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

University of Mississippi Medical Center - Baston Children's Hospital

Jackson, Mississippi, United States

Children's Mercy Hospital

Kansas City, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Nationwide Childrens Hospital

Columbus, Ohio, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

University of Virginia Health Systems (UVA)

Charlottesville, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Children's Hospital of Wisconsin

Wauwatosa, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RIV-PN-201

Identifier Type: -

Identifier Source: org_study_id