Roberta A Ballard1, Roberta L Keller2, Dennis M Black3, Philip L Ballard2, Jeffrey D Merrill4, Eric C Eichenwald5, William E Truog6, Mark C Mammel7, Robin H Steinhorn8, Elizabeth E Rogers2, Rita M Ryan9, David J Durand4, Jeanette M Asselin4, Catherine M Bendel10, Ellen M Bendel-Stenzel11, Sherry E Courtney12, Ramasubbareddy Dhanireddy13, Mark L Hudak14, Frances R Koch9, Dennis E Mayock15, Victor J McKay16, T Michael O'Shea17, Nicolas F Porta18, Rajan Wadhawan19, Lisa Palermo3. 1. Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA. Electronic address: ballardr@peds.ucsf.edu. 2. Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA. 3. Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA. 4. Department of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, CA. 5. Department of Pediatrics, The University of Texas Health Science Center Houston, Houston, TX. 6. Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO. 7. Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, St Paul, MN. 8. Department of Pediatrics, UC Davis Children's Hospital, Sacramento, CA. 9. Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 10. Department of Pediatrics, University of Minnesota Amplatz Children's Hospital, Minneapolis, MN. 11. Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN. 12. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR. 13. Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN. 14. Department of Pediatrics, University of Florida College of Medicine-Jacksonville, Jacksonville, FL. 15. Department of Pediatrics, University of Washington, Seattle, WA. 16. Department of Pediatrics, All Children's Hospital, St Petersburg, FL. 17. Department of Pediatrics, Wake Forest School of Medicine and Forsyth Medical Center, Winston-Salem, NC. 18. Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL. 19. Department of Pediatrics, Florida Hospital for Children, Orlando, FL.
Abstract
OBJECTIVE: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). STUDY DESIGN:Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. RESULTS: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. CONCLUSION: Late treatment with up to 5 doses of surfactant in ventilated premature infants receivinginhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.
RCT Entities:
OBJECTIVE: To assess whether late surfactant treatment in extremely low gestational age (GA) newborn infants requiring ventilation at 7-14 days, who often have surfactant deficiency and dysfunction, safely improves survival without bronchopulmonary dysplasia (BPD). STUDY DESIGN: Extremely low GA newborn infants (GA ≤28 0/7 weeks) who required mechanical ventilation at 7-14 days were enrolled in a randomized, masked controlled trial at 25 US centers. All infants received inhaled nitric oxide and either surfactant (calfactant/Infasurf) or sham instillation every 1-3 days to a maximum of 5 doses while intubated. The primary outcome was survival at 36 weeks postmenstrual age (PMA) without BPD, as evaluated by physiological oxygen/flow reduction. RESULTS: A total of 511 infants were enrolled between January 2010 and September 2013. There were no differences between the treated and control groups in mean birth weight (701 ± 164 g), GA (25.2 ± 1.2 weeks), percentage born at GA <26 weeks (70.6%), race, sex, severity of lung disease at enrollment, or comorbidities of prematurity. Survival without BPD did not differ between the treated and control groups at 36 weeks PMA (31.3% vs 31.7%; relative benefit, 0.98; 95% CI, 0.75-1.28; P = .89) or 40 weeks PMA (58.7% vs 54.1%; relative benefit, 1.08; 95% CI, 0.92-1.27; P = .33). There were no between-group differences in serious adverse events, comorbidities of prematurity, or severity of lung disease to 36 weeks. CONCLUSION: Late treatment with up to 5 doses of surfactant in ventilated premature infants receiving inhaled nitric oxide was well tolerated, but did not improve survival without BPD at 36 or 40 weeks. Pulmonary and neurodevelopmental assessments are ongoing. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01022580.
Authors: Katherine C Wai; Anna M Hibbs; Martina A Steurer; Dennis M Black; Jeanette M Asselin; Eric C Eichenwald; Philip L Ballard; Roberta A Ballard; Roberta L Keller Journal: J Pediatr Date: 2018-04-04 Impact factor: 4.406
Authors: Roberta L Keller; Eric C Eichenwald; Anna Maria Hibbs; Elizabeth E Rogers; Katherine C Wai; Dennis M Black; Philip L Ballard; Jeanette M Asselin; William E Truog; Jeffrey D Merrill; Mark C Mammel; Robin H Steinhorn; Rita M Ryan; David J Durand; Catherine M Bendel; Ellen M Bendel-Stenzel; Sherry E Courtney; Ramasubbareddy Dhanireddy; Mark L Hudak; Frances R Koch; Dennis E Mayock; Victor J McKay; Jennifer Helderman; Nicolas F Porta; Rajan Wadhawan; Lisa Palermo; Roberta A Ballard Journal: J Pediatr Date: 2017-01-16 Impact factor: 4.406
Authors: Katherine C Wai; Michael A Kohn; Roberta A Ballard; William E Truog; Dennis M Black; Jeanette M Asselin; Philip L Ballard; Elizabeth E Rogers; Roberta L Keller Journal: J Pediatr Date: 2016-07-26 Impact factor: 4.406
Authors: Judith A Voynow; Kimberley Fisher; Mary E Sunday; Charles M Cotten; Aaron Hamvas; Karen D Hendricks-Muñoz; Brenda B Poindexter; Gloria S Pryhuber; Clement L Ren; Rita M Ryan; Jack K Sharp; Sarah P Young; Haoyue Zhang; Rachel G Greenberg; Amy H Herring; Stephanie D Davis Journal: Pediatr Pulmonol Date: 2020-01-29
Authors: Bernard Thébaud; Kara N Goss; Matthew Laughon; Jeffrey A Whitsett; Steven H Abman; Robin H Steinhorn; Judy L Aschner; Peter G Davis; Sharon A McGrath-Morrow; Roger F Soll; Alan H Jobe Journal: Nat Rev Dis Primers Date: 2019-11-14 Impact factor: 52.329
Authors: Dara G Torgerson; Philip L Ballard; Roberta L Keller; Sam S Oh; Scott Huntsman; Donglei Hu; Celeste Eng; Esteban G Burchard; Roberta A Ballard Journal: Am J Physiol Lung Cell Mol Physiol Date: 2018-08-16 Impact factor: 5.464
Authors: Shabih U Hasan; Jim Potenziano; Girija G Konduri; Jose A Perez; Krisa P Van Meurs; M Whit Walker; Bradley A Yoder Journal: JAMA Pediatr Date: 2017-11-01 Impact factor: 16.193