Persistent Pulmonary HypertensionPhase 2NCT01409031
Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension
A Phase 2 study testing Intravenous Sildenafil in people with Persistent Pulmonary Hypertension and Respiratory Failure, run by University of Colorado, Denver at 7 sites in United States.
Trial summary
The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension. Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Persistent Pulmonary Hypertension, Respiratory Failure
- What is being tested?
- Intravenous Sildenafil
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 7 sitesUnited States
- Study dates
- Jul 2011to Oct 2013
- 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 Up to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Signed informed consent from legally acceptable guardian
- PPHN or hypoxemic respiratory failure associated with:
- Idiopathic PPHN
- Meconium aspiration syndrome
- Respiratory distress syndrome
- Sepsis
Show all 13Show fewer
- Pneumonia
- Greater than or equal to 35 weeks gestation
- Age at enrollment less than 72 hours
- Moderate hypoxemic respiratory failure, with 12<OI<35 (oxygenation index, calculated as FiO2 * mean airway pressure * 100 / postductal PaO2)
- Absence of structural heart disease (except patent ductus arteriosus, atrial septal defect <1cm, or muscular ventricular septal defect < 2mm)
- Absence of lethal congenital anomaly
- Not participating in another concurrent experimental study
Who cannot join
- Prior or immediate need for iNO or ECMO
- Profound hypoxemia: qualifying PaO2 <30 mmHg, from a blood gas drawn within 30 minutes of starting study drug infusion.
- Hypotension: Mean arterial pressure <35 mmHg
- Congenital heart disease, except patent ductus arteriosus, atrial septal defect <1cm, or muscular ventricular septal defect <2mm
- Congenital diaphragmatic hernia or lung hypoplasia syndromes, diagnosed on the basis of prolonged oligohydramnios
- Active seizures
Show all 15Show fewer
- Apgar score of <3 at 5 minutes
- Bleeding diathesis
- Receipt of any other experimental drug or device
- Receipt of any prohibited concurrent medication:
- Potent cytochrome P450 3A4 inhibitors (e.g., erythromycin, ketoconazole, itraconazole and protease inhibitors)
- Endothelin antagonists (e.g. Tracleer/bosentan)
- Intravenous nitrates or nitric oxide donors
- Known hereditary degenerative retinal disorders such as retinitis pigmentosa.
- In the opinion of the investigator, a subject who is not likely to complete the study or would be considered inappropriate for the study, for any reason.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Colorado Health Sciences Center
Aurora, Colorado, 80045
Women's & Children's Hospital of Buffalo SUNY
Buffalo, New York, 14222
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Anne and Robert H Lurie Children's Hospital of Chicago
Chicago, Illinois, 60614
Vanderbilt University
Nashville, Tennessee, 37232
Primary Children's Medical Center, Utah
Salt Lake City, Utah, 84113
University of Utah
Salt Lake City, Utah, 84132
About this study
Official title: Phase II Trial of Sildenafil in Newborns With Persistent Pulmonary Hypertension
The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension.
Read the detailed description
Term infants with respiratory failure and persistent pulmonary hypertension (PPHN) are among the most critically ill infants in the NICU, with significant mortality and morbidity reported even for infants with moderate disease. Currently, management is largely supportive, and includes oxygen, mechanical ventilation (conventional or high frequency ventilation), and exogenous surfactant therapy. Inhaled nitric oxide (iNO) is a pulmonary vasodilator that was approved for the treatment of hypoxic respiratory failure (HRF) and PPHN of the newborn in 1999 based on clinical trials showing a reduction in the need for rescue treatment with extracorporeal membrane oxygenation (ECMO).
One promising therapy to decrease pulmonary arterial pressure and improve oxygenation is sildenafil. Sildenafil is a cGMP-specific phosphodiesterase inhibitor that causes relatively selective pulmonary vasodilation. The use of intravenous (IV) sildenafil was recently FDA approved for use in adults in PPHN. A pilot trial studying dose response and pharmacokinetics in 36 term newborns with PPHN found that IV sildenafil was well tolerated and has the potential to induce marked improvements in oxygenation. The data from this pilot trial provided background to support the dosing regimen for this Phase II trial. We hypothesize that IV sildenafil will acutely reduce pulmonary artery pressure and improve oxygenation in near-term and term infants with PPHN, thus reducing the need for rescue therapy iNO and/or ECMO.
- Being tested
- Intravenous Sildenafil, Placebo
- Keywords
- newborns, respiratory failure, pulmonary hypertension, treatment
- Medical subject headings
- Respiratory Insufficiency, Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous SildenafilDrug
Also called Revatio
0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.
PlaceboOther
An equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Sildenafil | Experimental | Not described Receives: Drug: Intravenous Sildenafil |
| Placebo | Placebo comparator | 0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in Oxygenation
Measured: From baseline values at 4 and 24 hours
Receipt of Standard Therapy at Any Point During the 7-day Treatment Period
Receipt of standard therapy (inhaled nitric oxide [iNO] and/or extracorporeal membrane oxygenation [ECMO]) at any point during the 7-day treatment period
Measured: 7-day treatment period
Secondary outcomes (4)
Change in Pulmonary Arterial Pressure
Change in pulmonary arterial pressure as calculated by echocardiography
Measured: Baseline and 4 hours post study drug administration
Duration of Supplemental O2
Measured: Participants will be on supplemental O2 an average of 2 weeks
Age at Hospital Discharge
Measured: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Duration of Mechanical Ventilation
Measured: Participants will be on mechanical ventilation an average of 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2011 (estimated)
- Study startJul 2011
- Primary completionOct 2013
- Study completionOct 2013
Why it stopped: This trial was terminated early due to lack of recruitment.
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 HypertensionStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), State University of New York at Buffalo, Vanderbilt University, Ann & Robert H Lurie Children's Hospital of Chicago, University of Utah, University of Alabama at Birmingham
- Responsible party
- Sponsor
- Investigators
- John Kinsella, MD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01409031
- Sponsor's protocol ID
- 10-1211
- Other IDs
- 1U01HL102235
- Status last verified
- Jan 2019
- First submitted
- 15 Jul 2011
- Last updated
- 1 Feb 2019
- 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 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Sildenafil in Newborns With Persistent Pulmonary Hypertension
- ClinicalTrials.gov ID
- NCT01409031
- Acronym / sponsor ID
- 10-1211
- Keywords
- newborns, respiratory failure, pulmonary hypertension, treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This trial was terminated early due to lack of recruitment.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), State University of New York at Buffalo, Vanderbilt University, Ann & Robert H Lurie Children's Hospital of Chicago, University of Utah, University of Alabama at Birmingham
- Study start
- Jul 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 3 Aug 2011 (estimated)
- Results
- Posted 1 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether intravenous sildenafil reduces pulmonary artery pressure and improves oxygenation in near-term and term infants with persistent pulmonary hypertension.
Detailed description
Term infants with respiratory failure and persistent pulmonary hypertension (PPHN) are among the most critically ill infants in the NICU, with significant mortality and morbidity reported even for infants with moderate disease. Currently, management is largely supportive, and includes oxygen, mechanical ventilation (conventional or high frequency ventilation), and exogenous surfactant therapy. Inhaled nitric oxide (iNO) is a pulmonary vasodilator that was approved for the treatment of hypoxic respiratory failure (HRF) and PPHN of the newborn in 1999 based on clinical trials showing a reduction in the need for rescue treatment with extracorporeal membrane oxygenation (ECMO).
One promising therapy to decrease pulmonary arterial pressure and improve oxygenation is sildenafil. Sildenafil is a cGMP-specific phosphodiesterase inhibitor that causes relatively selective pulmonary vasodilation. The use of intravenous (IV) sildenafil was recently FDA approved for use in adults in PPHN. A pilot trial studying dose response and pharmacokinetics in 36 term newborns with PPHN found that IV sildenafil was well tolerated and has the potential to induce marked improvements in oxygenation. The data from this pilot trial provided background to support the dosing regimen for this Phase II trial. We hypothesize that IV sildenafil will acutely reduce pulmonary artery pressure and improve oxygenation in near-term and term infants with PPHN, thus reducing the need for rescue therapy iNO and/or ECMO.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Sildenafil | Experimental | Drug: Intravenous Sildenafil |
| Placebo | Placebo comparator | Other: Placebo0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (13 listed)
- Signed informed consent from legally acceptable guardian
- PPHN or hypoxemic respiratory failure associated with:
- Greater than or equal to 35 weeks gestation
- Age at enrollment less than 72 hours
- Moderate hypoxemic respiratory failure, with 12<OI<35 (oxygenation index, calculated as FiO2 * mean airway pressure * 100 / postductal PaO2)
Key exclusion criteria (15 listed)
- Prior or immediate need for iNO or ECMO
- Profound hypoxemia: qualifying PaO2 <30 mmHg, from a blood gas drawn within 30 minutes of starting study drug infusion.
- Hypotension: Mean arterial pressure <35 mmHg
- Congenital heart disease, except patent ductus arteriosus, atrial septal defect <1cm, or muscular ventricular septal defect <2mm
- Congenital diaphragmatic hernia or lung hypoplasia syndromes, diagnosed on the basis of prolonged oligohydramnios
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 |
|---|---|---|
| Intravenous SildenafilAlso: Revatio0.4 mg/kg bolus, followed by a continuous infusion of 1.6 mg/kg/day or an equivalent volume of placebo (D5W); infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. | Drug | Intravenous Sildenafil |
| PlaceboAn equivalent volume of placebo (D5W)infusion will be initiated as a bolus over 3 hours, followed by a controlled continuous infusion for up to 7 days. | Other | Placebo |
Primary outcome
Improvement in Oxygenation
Time frame: From baseline values at 4 and 24 hours
Receipt of Standard Therapy at Any Point During the 7-day Treatment Period
Time frame: 7-day treatment period
Receipt of standard therapy (inhaled nitric oxide [iNO] and/or extracorporeal membrane oxygenation [ECMO]) at any point during the 7-day treatment period
4 secondary outcomes
Change in Pulmonary Arterial Pressure
Time frame: Baseline and 4 hours post study drug administration
Duration of Supplemental O2
Time frame: Participants will be on supplemental O2 an average of 2 weeks
Age at Hospital Discharge
Time frame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks
Duration of Mechanical Ventilation
Time frame: Participants will be on mechanical ventilation an average of 1 week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Persistent Pulmonary Hypertension
Active, not recruitingPhase 2
Effect of a Parenteral Emulsion With Omega3 on Neonates With PPHN and CDH
Pulmonary Hypertension of Newborn, Diaphragm Defect
Recruiting
Effect of Melatonin on Pulmonary Hypertension in Full Term Neonates
Congenital Peumonia, Persistent Pulmonary Hypertension of Newborn
Enrolling by invitation
Pressure Regulated Volume Control Ventilation in Neonates Persistent Pulmonary Hypertension
Persistent Pulmonary Hypertension, Mechanical Ventilation Strategies
Not yet recruitingObservational study
Post Market Clinical Follow-up to Assess the Portable Nitric Oxide Generation and Delivery System (INOwill N200) for the Treatment of Neonatal Hypoxic Respiratory Failure Complicated by Pulmonary Hypertension
Persistent Pulmonary Hypertension of the Newborn, Hypoxic Respiratory Failure
Not yet recruitingObservational study
Predictors of Outcomes in Pulmonary Hypertension of the Newborn
Hypertension, Pulmonary, Infant, Newborn, Diseases
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.
John Kinsella, MD principal investigator
University of Colorado, Denver
7 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 Intravenous Sildenafil in people with Persistent Pulmonary Hypertension and Respiratory Failure, run by University of Colorado, Denver at 7 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 13 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 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 1 Feb 2019). 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?
Improvement in Oxygenation (time frame: From baseline values at 4 and 24 hours). The study lists 2 primary outcomes in all. 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 1 Feb 2019.