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

Persistent Pulmonary Hypertension of the Newborn Clinical Trial

Official title:

Intravenous Remodulin (Treprostinil) as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn: A Randomized, Placebo-Controlled, Safety and Efficacy Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02261883
• Other study ID #: RIV-PN-201
• Status: Terminated
• Phase: Phase 2
• Start date: July 29, 2015
• Est. completion date: May 17, 2023

Study information

• Verified date: February 2024
• Source: United Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 42
• Est. completion date: May 17, 2023
• Est. primary completion date: September 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Hour to 14 Days

Eligibility

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Persistent Fetal Circulation Syndrome
• Persistent Pulmonary Hypertension of the Newborn

Intervention

Drug:
• IV Remodulin
Treprostinil is a chemically stable tricyclic analogue of prostacyclin.
• Placebo
Sodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous).

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Virginia Health Systems (UVA)	Charlottesville	Virginia
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Mississippi Medical Center - Baston Children's Hospital	Jackson	Mississippi
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Columbia University Medical Center	New York	New York
United States	Stanford Children's Hospital	Palo Alto	California
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's Hospital of Wisconsin	Wauwatosa	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
United Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Oxygenation Index (OI)	OI is an assessment of how much oxygen from the lungs enters the blood when a subject inhales, calculated as: mean airway pressure (MAP) multiplied by fraction of inspired oxygen (FiO2) divided by partial pressure of oxygen in the arterial blood (PaO2), then multiplying by 100. An OI of 15 or less indicates mild hypoxia, 16 to 25 indicates moderate hypoxia, 26 to 40 indicates severe hypoxia, and more than 40 indicates very severe hypoxia.	From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning
Secondary	Change in P/F Ratio	PaO2/FiO2 ratio, also referred to as P/F Ratio, is a calculation used to assess the severity of hypoxemia, which is a condition characterized by low levels of oxygen in the blood. A low P/F ratio suggests that the patient's oxygen levels are compromised relative to the amount of oxygen being provided.	From Baseline to Hours 12, 24, and 72
Secondary	Change in Pre- and Post-ductal Oxygen Saturation (SpO2)	SpO2 is an assessment of how much oxygen is in the blood, measured by a pulse oximeter. Pre-ductal SpO2 is measured in the right hand or foot and is a reflection of the amount of oxygen flowing to the brain. Post-ductal SpO2 is measured in the left hand or foot, after the blood has mixed with less oxygenated blood from the rest of the body.	From Baseline to Hours 6, 12, 24, and 72
Secondary	Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)	NT-proBNP is a hormone produced by the heart. Increased NT-proBNP concentration is associated with changes in right heart morphology and function. The main purpose of NT-proBNP testing is to see if the blood levels of this protein are within the expected range for a healthy individual.	From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge)
Secondary	Time to Clinical Worsening	Clinical worsening was assessed continuously during the study. 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 56
Secondary	Time to Initiation of ECMO	Start of ECMO was assessed continuously during the study. ECMO is a life-support therapy that oxygenates blood by passing it through an artificial lung. The start time of ECMO, if needed, was recorded for each subject.	From Baseline to Day 56
Secondary	Time to Discontinuation of Inhaled Nitric Oxide (iNO)	Discontinuation of iNO was assessed continuously during the study. iNO works by relaxing the blood vessels in the lungs, which makes it easier for oxygen to be delivered to the body. The stop time of iNO was recorded for each subject.	From Baseline to Day 56