Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia

NCT01022580 | Completed Phase 3 Results DMC

• 2 other identifiers: H10842-33541-01AU01HL094338
• Study Type: interventional
• Target: 511
• Locations: 1 country
• Sites: 21

Brief Summary

The purpose of this study is to determine if late doses of Infasurf surfactant given when patients are receiving inhaled nitric oxide will interact to improve surfactant function and increase survival without BPD in treated infants.

Conditions

Bronchopulmonary Dysplasia

Keywords

nitric oxide; surfactant; BPD; prematurity; neonates; iNO; pulmonary outcome; neurodevelopmental outcome; Infasurf; lung function; Surfactant Dysfunction; Bronchopulmonary Dysplasia

Outcome Measures

Primary Outcomes (1)

• Survival Without BPD at 36 Weeks Post Menstrual Age.

  BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction.

  36 weeks post menstrual age +/- 1 week

Secondary Outcomes (4)

• Survival Without BPD at 40 Weeks

  40 weeks PMA +/- 1 week

• Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age

  1 year

• Pulmonary Outcomes Through 2 Years of Age

  2 years

• Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years.

  2 years

Study Arms (2)

Infasurf surfactant (ONY, Inc.)

ACTIVE COMPARATOR

Infants already receiving inhaled nitric oxide will receive scheduled doses of late surfactant (Infasurf) on study days 0, 2, 4, 6 and 8.

Drug: Infasurf surfactant (ONY, Inc.)

Sham (No Treatment)

SHAM COMPARATOR

Infants already receiving inhaled nitric oxide will receive "Sham (no treatment)" doses on study days 0,2,4,6, and 8.

Drug: Sham (No Treatment)

Interventions

Infasurf surfactant (ONY, Inc.) DRUG

Late doses of Infasurf 3ml/kg will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.

Also known as: Treatment

Infasurf surfactant (ONY, Inc.)

Sham (No Treatment) DRUG

Late doses of Sham (No treatment) will be given to infants on study days 0, 2, 4, 6 and 8 as long as infant remains intubated.

Also known as: Control

Sham (No Treatment)

Eligibility Criteria

• Age: 7 Days - 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \<=28 0/7 weeks gestational age
• Day of life 7-14
• Intubated and mechanically ventilated
• Plan to treat with inhaled nitric oxide

You may not qualify if:

• Serious congenital malformations or chromosomal abnormalities
• Life expectancy \<7 days from enrollment
• Clinically unstable
• Less tha 48 hours since last dose surfactant
• Ability to obtain 36 week primary outcome information is unlikely

Sponsors & Collaborators

• Roberta Ballard: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (21)

University of Arkansas - Arkansas Childrens Hospital

Little Rock, Arkansas, 72202, United States

Location

Alta Bates Medical Center

Berkeley, California, 94705, United States

Location

Oakland Children's Hospital

Oakland, California, 94609, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Wolfson Children's Hospital and Shands HospitaL

Jacksonville, Florida, 32207, United States

Location

Florida Hospital for Children

Orlando, Florida, 32803, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Children's Memorial Hospital

Chicago, Illinois, 60614, United States

Location

Childrens Hospital and Clinics of Minnesota- Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

Location

Children's Hospital and Clinics of Minnesota - St Paul

Saint Paul, Minnesota, 55102, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Women's and Children's Hospital of Buffalo

Buffalo, New York, 14222, United States

Location

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

Location

Wake Forest University- Forsyth Hospital and Brenner Hospital

Winston-Salem, North Carolina, 27103, United States

Location

Medical University of South Carolina(MUSC)

Charleston, South Carolina, 29403, United States

Location

UT Memphis- Memphis Medical Center

Memphis, Tennessee, 38103-2807, United States

Location

UT Houston Health Science Center

Houston, Texas, 77030-1503, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Washington, Seattle

Seattle, Washington, 98195-6320, United States

Location

Related Publications (7)

• 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. doi: 10.1056/NEJMoa061088.

  PMID: 16870913 BACKGROUND

• 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. doi: 10.1542/peds.2007-0095.

  PMID: 17671061 BACKGROUND

• 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. doi: 10.1542/peds.2006-2683.

  PMID: 17403837 BACKGROUND

• Ballard RA, Keller RL, Black DM, Ballard PL, Merrill JD, Eichenwald EC, Truog WE, Mammel MC, Steinhorn RH, Rogers EE, Ryan RM, Durand DJ, Asselin JM, Bendel CM, Bendel-Stenzel EM, Courtney SE, Dhanireddy R, Hudak ML, Koch FR, Mayock DE, McKay VJ, O'Shea TM, Porta NF, Wadhawan R, Palermo L; TOLSURF Study Group. Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. J Pediatr. 2016 Jan;168:23-29.e4. doi: 10.1016/j.jpeds.2015.09.031. Epub 2015 Oct 21.

  PMID: 26500107 RESULT

• Wai KC, Hibbs AM, Steurer MA, Black DM, Asselin JM, Eichenwald EC, Ballard PL, Ballard RA, Keller RL; Trial of Late Surfactant (TOLSURF) Study Group. Maternal Black Race and Persistent Wheezing Illness in Former Extremely Low Gestational Age Newborns: Secondary Analysis of a Randomized Trial. J Pediatr. 2018 Jul;198:201-208.e3. doi: 10.1016/j.jpeds.2018.02.032. Epub 2018 Apr 4.

  PMID: 29627188 RESULT

• Keller RL, Eichenwald EC, Hibbs AM, Rogers EE, Wai KC, Black DM, Ballard PL, Asselin JM, Truog WE, Merrill JD, Mammel MC, Steinhorn RH, Ryan RM, Durand DJ, Bendel CM, Bendel-Stenzel EM, Courtney SE, Dhanireddy R, Hudak ML, Koch FR, Mayock DE, McKay VJ, Helderman J, Porta NF, Wadhawan R, Palermo L, Ballard RA; TOLSURF Study Group. The Randomized, Controlled Trial of Late Surfactant: Effects on Respiratory Outcomes at 1-Year Corrected Age. J Pediatr. 2017 Apr;183:19-25.e2. doi: 10.1016/j.jpeds.2016.12.059. Epub 2017 Jan 16.

  PMID: 28100402 RESULT

• Wai KC, Keller RL, Lusk LA, Ballard RA, Chan DK; Trial of Late Surfactant (TOLSURF) Study Group. Characteristics of Extremely Low Gestational Age Newborns Undergoing Tracheotomy: A Secondary Analysis of the Trial of Late Surfactant Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2017 Jan 1;143(1):13-19. doi: 10.1001/jamaoto.2016.2428.

  PMID: 27583380 DERIVED

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth; Surfactant Dysfunction

Interventions

Therapeutics; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Limitations and Caveats

Possible limitations of the trial: Infants 1) may not have had enough surfactant dysfunction to benefit from replacement; or 2) had irreversible lung damage prior to enrollment; or 3) The dose/frequency of replacement surfactant was inadequate.

Results Point of Contact

• Title: Roberta A Ballard, MD
• Organization: University of California, San Francisco

roberta.ballard@ucsf.edu

415-476-4193

Study Officials

• Roberta A Ballard, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: November 19, 2009
• First Posted: December 1, 2009
• Study Start: January 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: January 1, 2016
• Last Updated: May 13, 2021
• Results First Posted: May 13, 2021

Record last verified: 2021-04

Locations

US (21)