Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension
This study is currently recruiting participants.
Verified May 2012 by National Heart, Lung, and Blood Institute (NHLBI)
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT01409031
First received: July 15, 2011
Last updated: May 4, 2012
Last verified: May 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Persistent Pulmonary Hypertension Respiratory Failure |
Drug: Intravenous Sildenafil Other: Placebo |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Phase II Trial of Sildenafil in Newborns With Persistent Pulmonary Hypertension |
Resource links provided by NLM:
Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):
Primary Outcome Measures:
- Improvement in oxygenation [ Time Frame: From baseline values at 4 and 24 hours ] [ Designated as safety issue: No ]
- Receipt of standard therapy at any point during the 7-day treatment period [ Time Frame: 7-day treatment period ] [ Designated as safety issue: No ]Receipt of standard therapy (inhaled nitric oxide [iNO] and/or extracorporeal membrane oxygenation [ECMO]) at any point during the 7-day treatment period
Secondary Outcome Measures:
- Change in pulmonary arterial pressure [ Time Frame: Baseline and 4 hours post study drug administration ] [ Designated as safety issue: No ]Change in pulmonary arterial pressure as calculated by echocardiography
- Duration of supplemental O2 [ Time Frame: Participants will be on supplemental O2 an average of 2 weeks ] [ Designated as safety issue: No ]
- Age at hospital discharge [ Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 3 weeks ] [ Designated as safety issue: No ]
- Duration of mechanical ventilation [ Time Frame: Participants will be on mechanical ventilation an average of 1 week ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 50 |
| Study Start Date: | July 2011 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Intravenous Sildenafil |
Drug: Intravenous Sildenafil
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.
Other Name: Revatio
|
|
Placebo Comparator: Placebo
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.
|
Other: Placebo
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.
|
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.
Eligibility| Ages Eligible for Study: | up to 72 Hours |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Signed informed consent from legally acceptable guardian
PPHN or hypoxemic respiratory failure associated with:
- Idiopathic PPHN
- Meconium aspiration syndrome
- Respiratory distress syndrome
- Sepsis
- Pneumonia •≥35 weeks gestation
- Age at enrollment less than 72 hours
- Moderate hypoxemic respiratory failure, with 15<OI<25 (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
Exclusion Criteria:
- 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
- Apgar score of <3 at 5 minutes, or need for hypothermia treatment for neonatal encephalopathy
- 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.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01409031
Contacts
| Contact: John Kinsella, MD | 303-724-2853 | John.Kinsella@ucdenver.edu |
| Contact: Lucy Fashaw, RNC | 720-777-6745 | Lucy.Fashaw@ucdenver.edu |
Locations
| United States, Colorado | |
| University of Colorado Health Sciences Center | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| Contact: John Kinsella, MD 303-724-2853 John.Kinsella@ucdenver.edu | |
| Principal Investigator: John Kinsella, MD | |
| United States, Illinois | |
| Children's Memorial Hospital | Recruiting |
| Chicago, Illinois, United States, 60614 | |
| Contact: Robin Steinhorn, MD r-steinhorn@northwestern.edu | |
| Principal Investigator: Robin Steinhorn, MD | |
| Northwestern Memorial Hospital | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Robin Steinhorn, MD r-steinhorn@northwestern.edu | |
| Principal Investigator: Robin Steinhorn, MD | |
| United States, New York | |
| Women's & Children's Hospital of Buffalo SUNY | Recruiting |
| Buffalo, New York, United States, 14222 | |
| Contact: Satyanarayana Lakshminrusima, MD slakshmi@buffalo.edu | |
| Principal Investigator: Satyanarayana Lakshminrusima, MD | |
| United States, Tennessee | |
| Vanderbilt University | Recruiting |
| Nashville, Tennessee, United States, 37232 | |
| Contact: William Walsh, MD bill.walsh@vanderbilt.edu | |
| Principal Investigator: William Walsh, MD | |
| United States, Utah | |
| University of Utah | Recruiting |
| Salt Lake City, Utah, United States, 84132 | |
| Contact: Bradley Yoder, MD bradley.yoder@hsc.utah.edu | |
| Principal Investigator: Bradley Yoder, MD | |
| Primary Children's Medical Center, Utah | Recruiting |
| Salt Lake City, Utah, United States, 84113 | |
| Contact: Bradley Yoder, MD bradley.yoder@hsc.utah.edu | |
| Principal Investigator: Bradley Yoder, MD | |
Sponsors and Collaborators
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
Investigators
| Principal Investigator: | John Kinsella, MD | University of Colorado, Denver |
More Information
No publications provided
| Responsible Party: | National Heart, Lung, and Blood Institute (NHLBI) |
| ClinicalTrials.gov Identifier: | NCT01409031 History of Changes |
| Other Study ID Numbers: | 1U01HL102235-01A1 |
| Study First Received: | July 15, 2011 |
| Last Updated: | May 4, 2012 |
| Health Authority: | United States: Federal Government United States: Food and Drug Administration |
Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
|
newborns respiratory failure pulmonary hypertension treatment |
Additional relevant MeSH terms:
|
Hypertension Hypertension, Pulmonary Respiratory Insufficiency Vascular Diseases Cardiovascular Diseases Lung Diseases Respiratory Tract Diseases Respiration Disorders Sildenafil |
Vasodilator Agents Cardiovascular Agents Therapeutic Uses Pharmacologic Actions Phosphodiesterase 5 Inhibitors Phosphodiesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013