Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia

Bronchopulmonary Dysplasia Clinical Trial

— TOLSURF  

Official title:

Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia: A Study in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01022580
• Other study ID #: H10842-33541-01A
• Secondary ID: U01HL094338
• Status: Completed
• Phase: Phase 3
• Start date: January 2010
• Est. completion date: January 2016

Study information

• Verified date: April 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

This is a multi-center, blinded, randomized controlled clinical trial to evaluate the effects of booster doses of exogenous surfactant (Infasurf®, calfactant) in addition to inhaled nitric oxide (iNO) on the outcome of survival without bronchopulmonary dysplasia (BPD, or chronic lung disease of prematurity, characterized by chronic lung dysfunction) at 36 weeks' post-menstrual age (PMA) in extremely low gestational age (ELGAN) infants that are at high risk of the development of BPD. This multi-center trial, with a planned enrollment of 524 infants, will also enable us to evaluate for any adverse effects of late surfactant treatment on short- and long-term outcomes, as we will be collecting data on effects of dosing of late surfactant, co-morbidities of prematurity and neurodevelopmental and pulmonary outcome at 1 year and 24 months corrected age. In addition, we will collect biological specimens for evaluation of the effects of late surfactant replacement therapy (administered as described in this trial) on surfactant function and inflammatory markers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 511
• Est. completion date: January 2016
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 14 Days

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Hyperplasia

Intervention

Drug:
• Infasurf surfactant (ONY, Inc.)
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.
• Sham (No Treatment)
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.

Locations

Country	Name	City	State
United States	Alta Bates Medical Center	Berkeley	California
United States	Women's and Children's Hospital of Buffalo	Buffalo	New York
United States	Medical University of South Carolina(MUSC)	Charleston	South Carolina
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Texas Children's Hospital	Houston	Texas
United States	UT Houston Health Science Center	Houston	Texas
United States	Wolfson Children's Hospital and Shands HospitaL	Jacksonville	Florida
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Arkansas - Arkansas Childrens Hospital	Little Rock	Arkansas
United States	UT Memphis- Memphis Medical Center	Memphis	Tennessee
United States	Childrens Hospital and Clinics of Minnesota- Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical School	Minneapolis	Minnesota
United States	Oakland Children's Hospital	Oakland	California
United States	Florida Hospital for Children	Orlando	Florida
United States	Children's Hospital and Clinics of Minnesota - St Paul	Saint Paul	Minnesota
United States	All Children's Hospital	Saint Petersburg	Florida
United States	University of California, San Francisco	San Francisco	California
United States	University of Washington, Seattle	Seattle	Washington
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Wake Forest University- Forsyth Hospital and Brenner Hospital	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Roberta Ballard	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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 T — View Citation

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. — View Citation

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, He — View Citation

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. — View Citation

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: Sec — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Survival Without BPD at 40 Weeks	BPD was diagnosed as need for respiratory support with either positive pressure and/or oxygen as evaluated by physiological oxygen/flow reduction.	40 weeks PMA +/- 1 week
Secondary	Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age	Evaluation of respiratory outcome through the first 12 months after birth. questionnaires were administered by phone at 3,6,9 and 12 months to determine respiratory resource use (medications, home support, and hospitalization) No Pulmonary Morbidity (NoPM) was reported for infants who had no resource use in any quarter and Persistent PM was reported for infants having resource use in 3 or 4 quarters.	1 year
Secondary	Pulmonary Outcomes Through 2 Years of Age	Evaluation of pulmonary outcome at 24 months of age. Evaluation of persistent wheezing based on reported wheezing during both first and second year of life.	2 years
Secondary	Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years.	At 24 months corrected age, children underwent neuropsychological testing with the Bayley Scales of Infant Development-Third Edition (Bayley-3), and composite cognitive, language, and motor scores were collected as well as subscale scores in receptive and expressive speech and fine and gross motor. Infants with greater than one impairment as identified by testing were classified as having neurodevelopmental impairment.	2 years