Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn
Purpose
This pilot study aims to assess the safety and treatment effect of acute dosing with IV Remodulin in neonates with persistent pulmonary hypertension of the newborn (PPHN).
Condition
- Persistent Pulmonary Hypertension of the Newborn
Eligibility
- Eligible Ages
- Under 14 Days
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Parent(s) or guardian provides consent for the subject to participate, as per institutional policy
- At least 2 kg at Screening
- Gestational age ≥ 34 weeks and ≤ 14 days old at Screening
- Diagnosis of PPHN, which is either idiopathic in nature or associated with the following: meconium aspiration syndrome (MAS), pneumonia, respiratory distress syndrome (RDS), sepsis, birth hypoxia, perinatal encephalopathy or unilateral congenital diaphragmatic hernia (CDH)
- Currently requiring ventilator support
- Receiving iNO with two OIs of 15 or greater separated by at least 30 minutes after receiving iNO for at least 3 hours
- Echocardiographic 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 (PDE5i), endothelin receptor antagonist (ERA), or prostanoid
- Significant congenital heart disease (CHD) as detected by ECHO (excluding presence of minor defects such as small secundum atrial septal defect (ASD), minor valvular abnormalities, or expected transitional findings such as a patent foramen ovale (PFO), or patent ductus arteriosus (PDA). Subjects with small muscular, restrictive ventricular septal defect (VSD) may be enrolled
- Clinically significant, untreated active pneumothorax at Screening
- Evidence of clinically significant bleeding
- Necrotizing entercolitis; ≥ Bells stage II at Screening
- Uncontrolled hypotension; mean systemic pressures ≤ 35 mmHg at Screening.
- Uncontrolled coagulopathy and / or untreated thrombocytopenia; defined as <50,000 platelets /µL at Screening
- History of severe (Grade 3 or 4) intracranial hemorrhage
- Currently receiving ECMO or has immediate plans to initiate ECMO
- Expected duration on mechanical ventilation of less than 48 hours
- Life expectancy is less than two months or has a lethal chromosomal anomaly
- Contraindication to ECMO
- Bilateral congenital diaphragmatic hernia
- Active seizures at Screening
- Currently participating in another clinical drug study (excluding observational registries)
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator IV Remodulin |
IV Remodulin will be initiated at 1 ng/kg/min. The dose will be increased in up to 2 ng/kg/min increments every 2 hrs until the OI is <10 (in the absence of dose-limiting side effects). |
|
|
Placebo Comparator Placebo |
Placebo will be initiated at 1 ng/kg/min. The dose will be increased in up to 2 ng/kg/min increments every 2 hrs until the OI is <10 (in the absence of dose-limiting side effects). |
|
Recruiting Locations
Children's National and nearby locations
Children's National Medical Center
Washington, District of Columbia 20010
Washington, District of Columbia 20010
More Details
- NCT ID
- NCT02261883
- Status
- Recruiting
- Sponsor
- United Therapeutics
Detailed Description
This study will enroll subjects with PPHN who do not show an adequate response to inhaled nitric oxide with the hypothesis that the addition of intravenous (IV) Remodulin will reduce the rate of clinical worsening as compared to standard of care. Additionally, this study aims to evaluate the treatment effect of Remodulin and better understand the dosing and pharmacokinetics in the neonatal population.