Clinical trial NCT01022580: Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia
Official title: Trial of Late Surfactant for Prevention of Bronchopulmonary Dysplasia: A Study in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bronchopulmonary Dysplasia
Keywords: nitric oxide
surfactant
BPD
prematurity
neonates
iNO
pulmonary outcome
neurodevelopmental outcome
Infasurf
lung function
Surfactant Dysfunction
Bronchopulmonary Dysplasia
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2009-12-01
Enrollment: 511
Sex: ALL
Minimum age (years): 7
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival Without BPD at 36 Weeks Post Menstrual Age.
timeFrame: 36 weeks post menstrual age +/- 1 week
Secondary outcomes:
measure: Survival Without BPD at 40 Weeks
timeFrame: 40 weeks PMA +/- 1 week
measure: Respiratory Outcomes of TOLSURF Infants at 1 Year Corrected Age
timeFrame: 1 year
measure: Pulmonary Outcomes Through 2 Years of Age
timeFrame: 2 years
measure: Percentage of Participants With Neurodevelopmental Impairment (NDI) at 2 Years.
timeFrame: 2 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas - Arkansas Childrens Hospital
state: Arkansas
city: Berkeley
country: United States
facility: Alta Bates Medical Center
state: California
city: Oakland
country: United States
facility: Oakland Children's Hospital
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Jacksonville
country: United States
facility: Wolfson Children's Hospital and Shands HospitaL
state: Florida
city: Orlando
country: United States
facility: Florida Hospital for Children
state: Florida
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: Minneapolis
country: United States
facility: Childrens Hospital and Clinics of Minnesota- Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Saint Paul
country: United States
facility: Children's Hospital and Clinics of Minnesota - St Paul
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: Buffalo
country: United States
facility: Women's and Children's Hospital of Buffalo
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University- Forsyth Hospital and Brenner Hospital
state: North Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina(MUSC)
state: South Carolina
city: Memphis
country: United States
facility: UT Memphis- Memphis Medical Center
state: Tennessee
city: Houston
country: United States
facility: UT Houston Health Science Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: University of Washington, Seattle
state: Washington
Study officials:
affiliation: University of California, San Francisco
name: Roberta A Ballard, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1056/NEJMoa061088.
citation: 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.
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. doi: 10.1542/peds.2006-2683.
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 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.
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: 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.
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, 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.
citation: 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.