Persistent Pulmonary Hypertension of the NewbornPhase 2NCT02261883
Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn
A Phase 2 study testing IV Remodulin in people with Persistent Pulmonary Hypertension of the Newborn, run by United Therapeutics at 14 sites in United States.
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). Read more about this study
- Who is it for?
- Ages 1 hour to 14 days
- Conditions the study is for
- Persistent Pulmonary Hypertension of the Newborn
- What is being tested?
- IV Remodulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 14 sitesUnited States
- Study dates
- 29 Jul 2015to 17 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 hour to 14 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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)
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Virginia Health Systems (UVA)
Charlottesville, Virginia, 22908
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Nationwide Childrens Hospital
Columbus, Ohio, 43205
Cook Children's Medical Center
Fort Worth, Texas, 76104
University of Mississippi Medical Center - Baston Children's Hospital
Jackson, Mississippi, 39216
Children's Mercy Hospital
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Columbia University Medical Center
New York, New York, 10032-3784
Stanford Children's Hospital
Palo Alto, California, 94304
Seattle Children's Hospital
Seattle, Washington, 98105
All Children's Hospital
St. Petersburg, Florida, 33701
Children's Hospital of Wisconsin
Wauwatosa, Wisconsin, 53226
About this study
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
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).
Read the 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).
- Being tested
- IV Remodulin, Placebo
- Keywords
- PPHN
- Medical subject headings
- Persistent Fetal Circulation Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV RemodulinDrug
Also called Treprostinil
Treprostinil is a chemically stable tricyclic analogue of prostacyclin.
PlaceboDrug
Sodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous).
| Study group | Role | What they receive |
|---|---|---|
| IV Remodulin | Active comparator | The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose. Receives: Drug: IV Remodulin |
| Placebo | Placebo comparator | The starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From Baseline to Day 14
Secondary outcomes (7)
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.
Measured: From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning
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.
Measured: From Baseline to Hours 12, 24, and 72
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.
Measured: From Baseline to Hours 6, 12, 24, and 72
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.
Measured: From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge)
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).
Measured: From Baseline to Day 56
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.
Measured: From Baseline to Day 56
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.
Measured: From Baseline to Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2014 (estimated)
- Study start29 Jul 2015
- Primary completion27 Sep 2022
- Study completion17 May 2023
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Persistent Pulmonary Hypertension of the NewbornStudies of the same condition, open and under way.
- More trials run by United TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- United Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02261883
- Sponsor's protocol ID
- RIV-PN-201
- Status last verified
- Feb 2024
- First submitted
- 30 Oct 2013
- Last updated
- 5 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02261883
- Acronym / sponsor ID
- RIV-PN-201
- Keywords
- PPHN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 42 participants (actual)
- Lead sponsor
- United TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2015 (actual)
- Primary completion
- 27 Sep 2022 (actual)
- Study completion
- 17 May 2023 (actual)
- First posted
- 10 Oct 2014 (estimated)
- Results
- Posted 5 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV Remodulin | Active comparator | Drug: IV RemodulinThe starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose. |
| Placebo | Placebo comparator | Drug: PlaceboThe starting dose was 1 ng/kg/min (not to exceed to 2 ng/kg/min) and was titrated by up to 2 ng/kg/min every 2 hours, as tolerated and clinically indicated by the Investigator. Doses were titrated and maximized throughout the study until the desired clinical effect was observed or to each individual subject's maximally tolerated dose. There was no maximum dose. |
Who may qualify
- Ages
- 1 hour to 14 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (15 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV RemodulinAlso: TreprostinilTreprostinil is a chemically stable tricyclic analogue of prostacyclin. | Drug | IV Remodulin |
| PlaceboSodium citrate, sodium chloride, sodium hydroxide pellets, metacresol, and citric acid (anhydrous). | Drug | Placebo |
Primary outcome
Number of Subjects Experiencing Clinical Worsening
Time frame: From Baseline to Day 14
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).
7 secondary outcomes
Change in Oxygenation Index (OI)
Time frame: From Baseline to Hours 12, 24, and 72; Days 7 and 14; and/or prior to study drug discontinuation/weaning
Change in P/F Ratio
Time frame: From Baseline to Hours 12, 24, and 72
Change in Pre- and Post-ductal Oxygen Saturation (SpO2)
Time frame: From Baseline to Hours 6, 12, 24, and 72
Change in N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP)
Time frame: From Baseline to Days 1, 2, 3, 7, and 14 (or prior to hospital discharge)
Time to Clinical Worsening
Time frame: From Baseline to Day 56
Time to Initiation of ECMO
Time frame: From Baseline to Day 56
Time to Discontinuation of Inhaled Nitric Oxide (iNO)
Time frame: From Baseline to Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV Remodulin in people with Persistent Pulmonary Hypertension of the Newborn, run by United Therapeutics at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects Experiencing Clinical Worsening (time frame: From Baseline to Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2024.