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

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ClinicalTrials.gov Identifier: NCT02261883
Recruitment Status : Recruiting
First Posted : October 10, 2014
Last Update Posted : April 14, 2022
Sponsor:
Information provided by (Responsible Party):
United Therapeutics

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Persistent Pulmonary Hypertension of the Newborn Drug: IV Remodulin Drug: Placebo Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : May 2015
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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).
 Drug: IV Remodulin
Treprostinil is a chemically stable tricyclic analogue of prostacyclin.
Other Name: treprostinil
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).
 Drug: Placebo
matching placebo


Outcome Measures
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Primary Outcome Measures :
  1. Evaluate the rate of clinical worsening in neonates with PPHN [ Time Frame: Up to Day 14 ]

    Efficacy will be assessed by a composite endpoint of clinical worsening as defined by the following:

    • Initiation of additional pulmonary vasodilator therapy
    • Initiation of extracorporeal mechanical oxygenation (ECMO) per institutional policies
    • Death


Secondary Outcome Measures :
  1. Time to discontinuation of inhaled nitric oxide (iNO) [ Time Frame: Up to Day 56 ]
  2. Change in oxygenation index (OI) [ Time Frame: Hour 12, hour 24, hour 72, Day 7 and Day 14/ or prior to study drug discontiuation ]
    OI= [MAP(mmHg) x FiO2(%) / PaO2(mmHg)] x 100

  3. Time on mechanical ventilation [ Time Frame: Up to Day 56 ]
  4. Time to initiation of ECMO [ Time Frame: Up to Day 56 ]
  5. Mean treprostinil plasma concentration per dose achieved [ Time Frame: 24 hours after initiation of Remodulin and immediately prior to wean ]
    Two blood samples will be collected from each patient for treprostinil pharmacokinetic (PK) analysis. Plasma samples will be analyzed for treprostinil using a validated bioanalytical plasma assay.

  6. Safety [ Time Frame: up to Day 56 ]
    Assessment of adverse events, change in vital signs, and change in labs.

  7. Change in partial pressure of oxygen in arterial blood (PaO2) / fraction of inspired oxygen (FiO2) [P/F ratio] [ Time Frame: Hour 12, hour 24, and hour 72 ]
  8. Change in N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) [ Time Frame: Day 7, Day 14, prior to study drug wean, study drug discontinuation ]
  9. Change in pre and post-ductal oxygen saturation (SpO2) [ Time Frame: Hour 6, hour 12, hour 24, and hour 72 ]

Eligibility Criteria
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Ages Eligible for Study:   1 Hour to 14 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02261883


Contacts
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Contact: United Therapeutics Global Medical Information 919-485-8350 clinicaltrials@unither.com

Locations
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Sponsors and Collaborators
United Therapeutics
More Information
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Publications:

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Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT02261883    
Other Study ID Numbers: RIV-PN-201
First Posted: October 10, 2014    Key Record Dates
Last Update Posted: April 14, 2022
Last Verified: April 2022
Keywords provided by United Therapeutics:
PPHN
Additional relevant MeSH terms:
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Hypertension, Pulmonary
Persistent Fetal Circulation Syndrome
Hypertension
Vascular Diseases
Cardiovascular Diseases
 Lung Diseases
Respiratory Tract Diseases
Infant, Newborn, Diseases
Treprostinil
Antihypertensive Agents