Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide (TOLSURFPilot)

• ClinicalTrials.gov Identifier: NCT00569530
• Recruitment Status: Completed
• First Posted: December 7, 2007
• Results First Posted: June 28, 2016
• Last Update Posted: June 28, 2016
• Sponsor: University of California, San Francisco
• Collaborators: Mallinckrodt; ONY
• Information provided by (Responsible Party): Roberta L. Keller, University of California, San Francisco

Study Description

Brief Summary:

The purpose of this study is to determine if the combination of late doses of Infasurf with inhaled nitric oxide will interact to improve the surfactant function and thus the respiratory status and outcome of treated infants.

Condition or disease	Intervention/treatment	Phase
Respiratory Distress Syndrome of Prematurity (Surfactant Dysfunction); Bronchopulmonary Dysplasia	Drug: Infasurf (ONY Inc.); Drug: Sham	Phase 3

Detailed Description:

Surfactant dysfunction my contribute to the development of bronchopulmonary dysplasia (BPD) in persistently ventilated preterm infants. We conducted a multi-center, randomized, blinded pilot study to assess the safety and efficacy of late administration of surfactant (Calfactant - high in protein B) in combination with prolonged inhaled nitric oxide in preterm infants < 1000 grams birthweight (BW). Calfactant is one of several types of exogenous surfactant. Calfactant has the highest % of surfactant protein B of the different types.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Trial of Late Surfactant to Prevent BPD: A Pilot Study in Ventilated Preterm Neonates Receiving Inhaled Nitric Oxide
• Study Start Date: January 2008
• Actual Primary Completion Date: December 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Treatment Surfactant (Infasurf) ONY, NY; Patients receive inhaled nitric oxide and scheduled doses of Infasurf on study days 0, 3, 7, 10, and 14, if infant remains ventilated.	Drug: Infasurf (ONY Inc.); Infasurf 3ml/kg will be given to infants on study days 0, 3, 7, 10, and 14, if remains intubated.; Other Name: Infasurf
Placebo Comparator: Sham (no treatment); Infants receiving inhaled nitric oxide will receive Sham (no treatment) on study days 0, 3, 7, 10, and 14, if infant remains ventilated.	Drug: Sham; Sham instillation (no treatment) will be given to study infants on days 0, 3, 7, 10, and 14, if remains intubated.; Other Name: Air

Outcome Measures

Primary Outcome Measures :

1. SP-B Content [ Time Frame: One day after dose ]
   SP-B Content is the surfactant protein B found in terms of percentage of phospholipid measured one day after surfactant or sham dose.

Secondary Outcome Measures :

1. Alive Without BPD at 36 Weeks Post Menstrual Age [ Time Frame: 36 Weeks Post Menstrual Age ]
   Alive without need for oxygen at 36 weeks post menstrual age.

Eligibility Criteria

• Ages Eligible for Study: up to 14 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Less than or equal to 1000 gm. birth weight
• Less than or equal to 30 weeks gestational age
• Day 7-14 of life
• Intubated and mechanically ventilated at any time days 7-14 of life

Exclusion Criteria:

• Serious congenital malformations
• Life expectancy less than 7 days from enrollment
• Previous treatment with iNO
• Active pulmonary hemorrhage at time of enrollment
• Active air leak syndrome at time of enrollment
• Bilateral grade IV intracranial hemorrhage prior to enrollment
• Less than 48 hours from last clinical dose of early surfactant.

Contacts and Locations

Locations

United States, California

Alta Bates Summit Medical Center

Berkeley, California, United States, 94705

Children's Hospital Oakland

Oakland, California, United States, 94609

University of California, San Francisco

San Francisco, California, United States, 94143

United States, Illinois

Northwestern Memorial Hospital

Chicago, Illinois, United States, 60611

Children's Memorial Hospital

Chicago, Illinois, United States, 60614

United States, Missouri

Children's Mercy Hospital

Kansas City, Missouri, United States, 64108

United States, New York

Women and Children's Hospital of Buffalo

Buffalo, New York, United States, 14222

Stony Brook University Medical Center

Stony Brook, New York, United States, 11794

United States, Texas

Texas Children's Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

University of California, San Francisco

Mallinckrodt

ONY

Investigators

• Principal Investigator: Roberta A Ballard, MD; University of California, San Francisco

More Information

Publications:

Ballard RA, Truog WE, Cnaan A, Martin RJ, Ballard PL, Merrill JD, Walsh MC, Durand DJ, Mayock DE, Eichenwald EC, Null DR, Hudak ML, Puri AR, Golombek SG, Courtney SE, Stewart DL, Welty SE, Phibbs RH, Hibbs AM, Luan X, Wadlinger SR, Asselin JM, Coburn CE; NO CLD Study Group. Inhaled nitric oxide in preterm infants undergoing mechanical ventilation. N Engl J Med. 2006 Jul 27;355(4):343-53. Erratum in: N Engl J Med. 2007 Oct 4;357(14):1444-5.

Ballard PL, Merrill JD, Truog WE, Godinez RI, Godinez MH, McDevitt TM, Ning Y, Golombek SG, Parton LA, Luan X, Cnaan A, Ballard RA. Surfactant function and composition in premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Aug;120(2):346-53.

Truog WE, Ballard PL, Norberg M, Golombek S, Savani RC, Merrill JD, Parton LA, Cnaan A, Luan X, Ballard RA; Nitric Oxide (to Prevent) Chronic Lung Disease Study Investigators. Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide. Pediatrics. 2007 Apr;119(4):670-8.

Keller RL, Merrill JD, Black DM, Steinhorn RH, Eichenwald EC, Durand DJ, Ryan RM, Truog WE, Courtney SE, Ballard PL, Ballard RA. Late administration of surfactant replacement therapy increases surfactant protein-B content: a randomized pilot study. Pediatr Res. 2012 Dec;72(6):613-9. doi: 10.1038/pr.2012.136. Epub 2012 Oct 4.

• Responsible Party: Roberta L. Keller, Principal Investigator, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00569530
• Other Study ID Numbers: H10842-31630-01; IND79367 ( Other Identifier: FDA )
• First Posted: December 7, 2007
• Results First Posted: June 28, 2016
• Last Update Posted: June 28, 2016
• Last Verified: May 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Roberta L. Keller, University of California, San Francisco:

nitric oxide; surfactant; bronchopulmonary dysplasia; prematurity; neonates; iNO; Infasurf; lung function; ventilated infants

Additional relevant MeSH terms:

Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome, Adult; Bronchopulmonary Dysplasia; Premature Birth; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Ventilator-Induced Lung Injury; Lung Injury; Nitric Oxide; Calfactant; Pulmonary Surfactants; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Free Radical Scavengers; Antioxidants; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Endothelium-Dependent Relaxing Factors; Vasodilator Agents; Gasotransmitters