Early Surfactant to Reduce Use of Mechanical Breathing in Low Birth Weight Infants

Condition(s) targeted: Infant, Newborn, Diseases; Respiratory Distress Syndrome; Respiratory Insufficiency

Intervention: Survanta (Drug); Continuous positive airway pressure (Procedure)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
Edward F. Donovan, MD, Principal Investigator, Affiliation: University of Cincinnati
Ann R. Stark, MD, Principal Investigator, Affiliation: Children's Hospital

Moderately premature infants with mild respiratory distress do not routinely receive artificial surfactant early in their course of treatment. To test whether they might benefit from early surfactant, infants who weigh 1250 to 2000 grams and have respiratory distress syndrome will be randomized to either receive surfactant as soon as possible after randomization, followed by extubation within 30 minutes and continuous positive airway pressure (CPAP) or surfactant according to the usual practice of the center. This trial will evaluate whether in infants with mild to moderate respiratory distress syndrome, early administration of surfactant followed by extubation within 30 minutes and the use of CPAP reduces the need for subsequent mechanical ventilation.

Official title: Immediate Extubation After the First Dose of Surfactant to Reduce the Use of Mechanical Ventilation

Study design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study

Detailed description: The role of surfactant therapy in the management of the larger infant with respiratory distress syndrome (RDS) remains unclear. In many neonatal intensive care units, these infants are routinely managed with CPAP alone. This trial will address whether early use of surfactant combined with CPAP will ameliorate the course of RDS without an increase in morbidity. Although the primary study outcomes are measures of use of mechanical ventilation, the focus of the study is not reduction in use of resources, but rather reduction in ventilator use and thereby likely reduction in risk of ventilator-associated morbidity.

Eligible infants will be randomized either to the intervention or control group. Infants in the intervention group will be treated with early surfactant followed by extubation within 30 minutes and application of CPAP. Infants in the control group will receive surfactant according to current center practice, only after initiation of mechanical ventilation. Randomization will be done as soon as possible after verification of eligibility, before the infant is 12 hours of age. Randomization will be stratified by clinical center and by birth weight.

The sample size of 560 infants (280 each in control and treatment groups) is based on an assumption of a relative risk reduction of 30 percent in ventilator use comparing the control and surfactant groups. A test with 80 percent power and 5 percent alpha level (two-tailed).

Minimum age: N/A. Maximum age: 12 Hours. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Birth weight 1250 to 2000 grams

- Age less than 12 hours

- Clinical and radiographic diagnosis of respiratory distress syndrome (RDS)

- Receiving supplemental oxygen with head-hood Fi02 of 0. 35 to 0. 50 or CPAP Fi02 of 0. 25

to 0. 50 to maintain oxygen saturation less than 90 percent and more than 96 percent

Exclusion Criteria:

- Receiving mechanical ventilation

- Air leak

- Pulmonary hemorrhage

- Major congenital anomaly

- Congenital non-bacterial infection

- Parental refusal of consent

- Refusal of attending neonatologist

University of Alabama, Birmingham, Alabama 35294, United States

Stanford University, Palo Alto, California 94304, United States

Yale University, New Haven, Connecticut 06520, United States

University of Miami, Miami, Florida 33101, United States

Emory University, Atlanta, Georgia 30335, United States

Indiana University, Indianapolis, Indiana 46202, United States

Wayne State University, Detroit, Michigan 48201, United States

University of New Mexico, Albuquerque, New Mexico 87131, United States

Case Western Reserve Univ, Cleveland, Ohio 44106, United States

University of Cincinnati, Cincinnati, Ohio 45267, United States

Women and Infants Hospital, Providence, Rhode Island 02903, United States

University of Tennessee, Memphis, Tennessee 38163, United States

University of Texas, Houston, Texas 77030, United States

For more information on this trial and the NICHD Neonatal Research Network.

For information on NICHD clinical trials.

Click here for a Cochrane review of "Early vs delayed selective surfactant treatment for neonatal respiratory distress syndrome."

Related publications:

Verder H, Robertson B, Greisen G, Ebbesen F, Albertsen P, Lundstrom K, Jacobsen T. Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. Danish-Swedish Multicenter Study Group. N Engl J Med. 1994 Oct 20;331(16):1051-5.

Starting date: May 2000
Last updated: February 21, 2007