Study of Sildenafil to Treat Newborns With Persistent Pulmonary Hypertension

NCT01409031 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 10-12111U01HL102235
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Persistent Pulmonary Hypertension; Respiratory Failure

Keywords

newborns; respiratory failure; pulmonary hypertension; treatment

Outcome Measures

Primary Outcomes (2)

• Improvement in Oxygenation

  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

  7-day treatment period

Secondary Outcomes (4)

• Change in Pulmonary Arterial Pressure

  Baseline and 4 hours post study drug administration

• Duration of Supplemental O2

  Participants will be on supplemental O2 an average of 2 weeks

• Age at Hospital Discharge

  Participants will be followed for the duration of hospital stay, an expected average of 3 weeks

• Duration of Mechanical Ventilation

  Participants will be on mechanical ventilation an average of 1 week

Study Arms (2)

Intravenous Sildenafil

EXPERIMENTAL

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.

Other: Placebo

Interventions

Intravenous Sildenafil DRUG

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.

Also known as: Revatio

Intravenous Sildenafil

Placebo OTHER

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.

Placebo

Eligibility Criteria

• Age: Up to 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Signed informed consent from legally acceptable guardian
• PPHN or hypoxemic respiratory failure associated with:
• Idiopathic PPHN
• Meconium aspiration syndrome
• Respiratory distress syndrome
• Sepsis
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• State University of New York at Buffalo: collaborator
• Vanderbilt University: collaborator
• Ann & Robert H Lurie Children's Hospital of Chicago: collaborator
• University of Utah: collaborator
• University of Alabama at Birmingham: collaborator

Study Sites (7)

University of Colorado Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Anne and Robert H Lurie Children's Hospital of Chicago

Chicago, Illinois, 60614, United States

Location

Women's & Children's Hospital of Buffalo SUNY

Buffalo, New York, 14222, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Primary Children's Medical Center, Utah

Salt Lake City, Utah, 84113, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Respiratory Insufficiency; Hypertension, Pulmonary

Interventions

Sildenafil Citrate

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Lung Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Given that this trial was stopped with only 3 patients randomized, the results are little more than anecdote except that the participants were randomized.

Results Point of Contact

• Title: John Kinsella, MD
• Organization: University of Colorado, Denver

John.Kinsella@ucdenver.edu

303-724-2853

Study Officials

• John Kinsella, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2011
• First Posted: August 3, 2011
• Study Start: July 1, 2011
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: February 1, 2019
• Results First Posted: February 1, 2019

Record last verified: 2019-01

Locations

US (7)