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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02261883
Other study ID # RIV-PN-201
Secondary ID
Status Terminated
Phase Phase 2
First received
Last updated
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
Health authority
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

Study Design


Related Conditions & MeSH terms


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
See also
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