Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide - 22/12/15

Doi : 10.1016/j.jpeds.2015.09.031

Roberta A. Ballard, MD ^1,^⁎ , Roberta L. Keller, MD ¹, Dennis M. Black, PhD ², Philip L. Ballard, MD, PhD ¹, Jeffrey D. Merrill, MD ³, Eric C. Eichenwald, MD ⁴, William E. Truog, MD ⁵, Mark C. Mammel, MD ⁶, Robin H. Steinhorn, MD ⁷, Elizabeth E. Rogers, MD ¹, Rita M. Ryan, MD ⁸, David J. Durand, MD ³, Jeanette M. Asselin, MS, RRT-NPS ³, Catherine M. Bendel, MD ⁹, Ellen M. Bendel-Stenzel, MD ¹⁰, Sherry E. Courtney, MD ¹¹, Ramasubbareddy Dhanireddy, MD ¹², Mark L. Hudak, MD ¹³, Frances R. Koch, MD ⁸, Dennis E. Mayock, MD ¹⁴, Victor J. McKay, MD ¹⁵, T. Michael O'Shea, MD ¹⁶, Nicolas F. Porta, MD ¹⁷, Rajan Wadhawan, MD ¹⁸, Lisa Palermo, MS ²
for the
TOLSURF Study Group^{^∗}
List of additional members of the TOLSURF Study Group are available at www.jpeds.com (Appendix 1).
S. Hamilton Strong, J. Immamura-Ching, M. Orfanos-Villalobos, C. Williams, D. Horton, L. Pacello, A. Willard, C. Gauldin, A. Holmes, P. Johnson, K. Meinert, A.M. Reynolds, MD, J. Lucie, P. Conway, M.l. Sacilowski, M. Leadersdorff, P. Orbank, K. Wynn, M. deUngria, MD, J. Khan, MD, K. Hamann, M. Schau, B. Hopkins, J. Jenson, C. Garcia, J. Shariff, R. McGovern, J. Adelman, A. Combs, M. Tjersland, S. Walker, E. Howland, J. Longoria, H. Meo, G. McDavid, K. Burson, R. Hinojosa, C. Johnson, K. Miller, S. Rogers, S. Wright, K. Barnette, A. Kellum, M. Burke, C. Hayes, S. Chadwick, D. Howard, C. Kennedy, R. Prince, B. Stefanescu, MD, J. Helderman, MD, K. Warden, P. Brown, J. Griffin, L. Conley, M. Georgieff, MD, B. Davern, M. Mills, S. Ritter, C. Wagner, MD, D. Fanning, J. Roberson, A. Lampland, MD, P. Meyers, A. Brey, C. Worwa, P. Dixon, G. Ebert, C. Hejl, M. Maxwell, K. McCullough, MT, M.T. El Abiad, MD, A. Talati, MD, S. Dempsey, K. Gammage, G. Gower, K. James, P. LeNoue, S. Bell, D. Bruton, M. Beaulieu, R. Williams, R. Barron-Nelson, S. Taylor, N.C. Sikes, G. Lowe, B. Proffitt, C. Chapin, H. Horneman, K. Hamann, S. Kelley, E. Vittinghoff, PhD, J. Hietpas, L. Denton, L. Wu, A. Jobe, MD, A. Fanaroff, MD, T. Clemons, L. Glantz, D. Reboussin, K. Van Meurs, MD, M. Allen, MD, B. Vohr, MD, R. Ballard, MD : Steering Committee, P. Ballard, MD, PhD : Steering Committee, C. Blaisdell, MD : Steering Committee, D. Durand, MD : Steering Committee, D. Black, PhD : Steering Committee, E. Eichenwald, MD : Steering Committee, R. Keller, MD : Steering Committee, M. Mammel, MD : Steering Committee, J. Merrill, MD : Steering Committee, E. Rogers, MD : Steering Committee, R. Ryan, MD : Steering Committee, W. Truog, MD : Steering Committee, J. Asselin : Steering Committee, N. Newton : Steering Committee

¹ Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, San Francisco, CA
² Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA
³ Department of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, CA
⁴ Department of Pediatrics, The University of Texas Health Science Center Houston, Houston, TX
⁵ Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO
⁶ Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, St Paul, MN
⁷ Department of Pediatrics, UC Davis Children's Hospital, Sacramento, CA
⁸ Department of Pediatrics, Medical University of South Carolina, Charleston, SC
⁹ Department of Pediatrics, University of Minnesota Amplatz Children's Hospital, Minneapolis, MN
¹⁰ Department of Pediatrics, Children's Hospitals and Clinics of Minnesota, Minneapolis, MN
¹¹ Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR
¹² Department of Pediatrics, The University of Tennessee Health Science Center, Memphis, TN
¹³ Department of Pediatrics, University of Florida College of Medicine–Jacksonville, Jacksonville, FL
¹⁴ Department of Pediatrics, University of Washington, Seattle, WA
¹⁵ Department of Pediatrics, All Children's Hospital, St Petersburg, FL
¹⁶ Department of Pediatrics, Wake Forest School of Medicine and Forsyth Medical Center, Winston-Salem, NC
¹⁷ Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL
¹⁸ Department of Pediatrics, Florida Hospital for Children, Orlando, FL

^∗Reprint requests: Roberta A. Ballard, MD, 3333 California St, Suite 150, San Francisco, CA 94118.

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 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.

Le texte complet de cet article est disponible en PDF.

Keyword : AE, BPD, DSMB, ELGAN, FiO₂, GA, iNO, IVH, NCPAP, NIH, NO CLD, PMA, SAE, SP-B, TA, TOLSURF

Plan

Methods

Study Efficacy Endpoints

Supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (U01-HL094338 and U01HL094355) and the UCSF Clinical and Translational Sciences Institute (UL1TR000004). ONY, Inc provided the Infasurf and IKARIA, Inc provided the inhaled nitric oxide, neither of which were involved in study design, collection, analysis, or interpretation of data, writing the manuscript or the decision to submit for publication. The authors declare no conflicts of interest.

Export

Vol 168

P. 23 - janvier 2016 Retour au numéro

Article précédent

Side Effects and Complications of Proton Pump Inhibitors: A Pediatric Perspective
Christopher M. Stark, Cade M. Nylund

| Article suivant

Weight Status in the First 2 Years of Life and Neurodevelopmental Impairment in Extremely Low Gestational Age Newborns
Mandy B. Belfort, Karl C.K. Kuban, T. Michael O'Shea, Elizabeth N. Allred, Richard A. Ehrenkranz, Stephen C. Engelke, Alan Leviton, Extremely Low Gestational Age Newborn (ELGAN) Study Investigators, Kathleen Lee, Anne McGovern, Jill Gambardella, Susan Ursprung, Ruth Blomquist Kristen Ecklund, Haim Bassan, Samantha Butler, Adré Duplessis, Cecil Hahn, Catherine Limperopoulos, Omar Khwaja, Janet S. Soul, Bhavesh Shah, Karen Christianson, Frederick Hampf, Herbert Gilmore, Susan McQuiston, Camilia R. Martin, Colleen Hallisey, Caitlin Hurley, Miren Creixell, Jane Share, Linda J. Van Marter, Sara Durfee, Robert M. Insoft, Jennifer G. Wilson, Maureen Pimental, Sjirk J. Westra, Kalpathy Krishnamoorthy, Cynthia Cole, John M. Fiascone, Janet Madden, Ellen Nylen, Anne Furey, Roy McCauley, Paige T. Church, Cecelia Keller, Karen J. Miller, Francis Bednarek, Mary Naples, Beth Powers, Jacqueline Wellman, Robin Adair, Richard Bream, Alice Miller, Albert Scheiner, Christy Stine, Richard Ehrenkranz, Joanne Williams, Elaine Romano, Cindy Miller, Nancy Close, T. Michael O'Shea, Debbie Gordon, Teresa Harold, Barbara Specter, Deborah Allred, Robert Dillard, Don Goldstein, Deborah Hiatt, Gail Hounshell, Ellen Waldrep, Lisa Washburn, Cherrie D. Welch, Stephen C. Engelke, Sherry Moseley, Linda Pare, Donna Smart, Joan Wilson, Ira Adler, Sharon Buckwald, Rebecca Helms, Kathyrn Kerkering, Scott S. MacGilvray, Peter Resnik, Carl Bose, Gennie Bose, Lynn A. Fordham, Lisa Bostic, Diane Marshall, Kristi Milowic, Janice Wereszczak, Mariel Poortenga, Dinah Sutton, Bradford W. Betz, Steven L. Bezinque, Joseph Junewick, Wendy Burdo-Hartman, Lynn Fagerman, Kim Lohr, Steve Pastyrnak, Dinah Sutton, Carolyn Solomon, Ellen Cavenagh, Victoria J. Caine, Nicholas Olomu, Joan Price, Nigel Paneth, Padmani Karna, Madeleine Lenski, Michael D. Schreiber, Grace Yoon, Kate Feinstein, Leslie Caldarelli, Sunila E. O'Connor, Michael Msall, Susan Plesha-Troyke, Daniel Batton, Beth Kring, Karen Brooklier, Beth Kring, Melisa J. Oca, Katherine M. Solomon

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide - 22/12/15

Abstract

Objective

Study design

Results

Conclusion

Trial registration

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL