Clinical trial NCT02261883: Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Persistent Pulmonary Hypertension of the Newborn
Keywords: PPHN
Lead sponsor: United Therapeutics
Sponsor class: INDUSTRY
First posted: 2014-10-10
Enrollment: 42
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Number of Subjects Experiencing Clinical Worsening
timeFrame: From Baseline to Day 14
Secondary outcomes:
measure: Change in Oxygenation Index (OI)
timeFrame: From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning
measure: Change in P/F Ratio
timeFrame: From Baseline to Hours 12, 24, and 72
measure: Change in Pre- and Post-ductal Oxygen Saturation (SpO2)
timeFrame: From Baseline to Hours 6, 12, 24, and 72
measure: Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
timeFrame: From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge)
measure: Time to Clinical Worsening
timeFrame: From Baseline to Day 56
measure: Time to Initiation of ECMO
timeFrame: From Baseline to Day 56
measure: Time to Discontinuation of Inhaled Nitric Oxide (iNO)
timeFrame: From Baseline to Day 56
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford Children's Hospital
state: California
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Jackson
country: United States
facility: University of Mississippi Medical Center - Baston Children's Hospital
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Nationwide Childrens Hospital
state: Ohio
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health Systems (UVA)
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Wauwatosa
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
References: