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

NCT02261883 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: RIV-PN-201
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 14

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).

Conditions

Persistent Pulmonary Hypertension of the Newborn

Keywords

PPHN

Outcome Measures

Primary Outcomes (1)

• Number of Subjects Experiencing Clinical Worsening

  Clinical worsening was a composite endpoint defined by the occurrence of 1 of the following: death, initiation of ECMO per institutional policies, or need for additional treatment (initiation of additional targeted pulmonary vasodilator therapy).

  From Baseline to Day 14

Secondary Outcomes (7)

• Change in Oxygenation Index (OI)

  From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning

• Change in P/F Ratio

  From Baseline to Hours 12, 24, and 72

• Change in Pre- and Post-ductal Oxygen Saturation (SpO2)

  From Baseline to Hours 6, 12, 24, and 72

• Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)

  From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge)

• Time to Clinical Worsening

  From Baseline to Day 56

Study Arms (2)

IV Remodulin

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Interventions

IV Remodulin DRUG

Treprostinil is a chemically stable tricyclic analogue of prostacyclin.

Also known as: Treprostinil

IV Remodulin

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 1 Hour - 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• United Therapeutics: lead

Study Sites (14)

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Children's Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

Stanford Children's Hospital

Palo Alto, California, 94304, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

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

Chicago, Illinois, 60611, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

University of Mississippi Medical Center - Baston Children's Hospital

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Columbia University Medical Center

New York, New York, 10032-3784, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Virginia Health Systems (UVA)

Charlottesville, Virginia, 22908, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Children's Hospital of Wisconsin

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Persistent Fetal Circulation Syndrome

Interventions

treprostinil

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Global Medical Information
• Organization: United Therapeutics Corp.

clinicaltrials@unither.com

919-485-8350

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 30, 2013
• First Posted: October 10, 2014
• Study Start: July 29, 2015
• Primary Completion: September 27, 2022
• Study Completion: May 17, 2023
• Last Updated: March 5, 2024
• Results First Posted: March 5, 2024

Record last verified: 2024-02

Locations

US (14)