Clinical trial NCT00767039: Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants
Official title: Phase 4 Study of Curosurf (Poractant) and Survanta (Beractant) Surfactant Treatment in Very Premature Infants With Respiratory Distress Syndrome.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Prematurity
Respiratory Distress Syndrome
Patent Ductus Arteriosus
Keywords: Very Premature
RDS
Surfactant
Lead sponsor: Boston Medical Center
Sponsor class: OTHER
Collaborators: name: Dey LP
First posted: 2008-10-06
Enrollment: 52
Sex: ALL
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Approval of surfactant by the FDA in 1989 for the treatment of Respiratory Distress Syndrome (RDS) in premature infants greatly improved survival rates. Newer surfactants approved by the FDA were more concentrated and had a more rapid onset of action. The overall efficacy of newer surfactants appeared similar until in 2004, Ramanathan and colleagues suggested that a double dose of Curosurf improved survival in infants 25-32 weeks gestational age, compared to infants treated with Survanta, the most commonly used surfactant preparation in the United States. While the data was suggestive, it was not clear that the improvement in survival was reproducible or that Curosurf was responsible for the improved survival rates.

The purpose of this study was to investigate the role of Curosurf in improving lung function and survival rates and reducing the complications of prematurity in very premature infants \< 30 weeks gestational age at birth.

Detailed description: Specific Aims:

* To determine whether there is a sustained difference in the level of respiratory support during the first 3 days of life in extremely premature infants treated with Curosurf versus Survanta
* To determine whether Curosurf is associated with a higher incidence of hemodynamically significant PDA, compared with Survanta
* To determine whether there is a difference in the cerebral blood flow response to Curosurf versus Survanta
* To determine whether there is a difference in morbidity in very premature infants treated with Curosurf versus Survanta

We reasoned that if Curosurf was primarily responsible for improved survival rates, compared with Survanta, then there should be a sustained improvement in respiratory function in the first three days of life, when the direct pulmonary effects of the surfactant preparations would be most easily detected. It was also possible that Curosurf and Survanta could have effects on other systems that could secondarily affect long-term survival of the infant. These other organ systems would include, but not be limited to, the development of a hemodynamically significant Patent Ductus Arteriosus, Intraventricular Hemorrhage or Periventricular Leukomalacia, or Necrotizing Enterocolitis. We propose to examine how surfactant administration affected the hemodynamic precursors of these common morbidities of very premature infants.

Eligibility criteria: Inclusion Criteria:

* \<29 6/7 and \>24 0/7 weeks gestational age
* Inborn at the participating institution enrolling the patient
* FIO2 \>25% and Intubated with mean airway pressure \> 5 cm H20
* \<8 hours age at randomization
* Signed informed consent from parent(s)

Exclusion Criteria:

* \<500 g birth weight
* \<24 0/7 weeks gestational age (best estimate)
* Prolonged Premature Rupture of membranes \>3 weeks (21 days)
* Apgar score \< 3 at 5 minutes
* Impending death anticipated within the first 3 days of life, moribund
* Severe congenital anomalies

Primary outcomes:
measure: Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
timeFrame: 48 hours after surfactant administration
measure: Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration
timeFrame: 72 hours after surfactant administration
measure: Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
timeFrame: 48 hours after surfactant administration
measure: Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration.
timeFrame: 72 hours after surfactant administration
Secondary outcomes:
measure: Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
timeFrame: 48 hours after surfactant administration
measure: Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
timeFrame: 72 hours after surfactant administration
measure: Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)
timeFrame: Hemodynamically significant PDA at > 2 days
measure: Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)
timeFrame: First hour after 2nd surfactant dose
measure: Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant
timeFrame: One hour following second surfactant dose at 12-24 hours after initial dose
measure: Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)
timeFrame: 36 weeks post menstrual age
measure: Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU.
timeFrame: NICU hospitalization, up to 42 weeks post menstrual age
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
Study officials:
affiliation: Boston Medical Center
name: Alan M Fujii, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fujii AM, Editorial. Is There Really A Clinical Difference In Surfactant Preparations? J Perinatol 2010; 30:698; doi:10,1038/jp.2010.90
citation: Fujii A. Editorial. Are all animal derived surfactants the same? The e-NeoResearch 2011; 1 (1); 50-51.
citation: Fujii AM, Carillo M. Animal-derived surfactant treatment of respiratory distress syndrome in premature neonates: a review. Drugs Today (Barc). 2009 Sep;45(9):697-709.
citation: Fujii AM, Patel SM, Allen R, Doros G, Guo CY, Testa S. Poractant alfa and beractant treatment of very premature infants with respiratory distress syndrome. J Perinatol. 2010 Oct;30(10):665-70. doi: 10.1038/jp.2010.20. Epub 2010 Mar 25.
citation: Fujii A, Allen R, Doros G, O'Brien S. Patent ductus arteriosus hemodynamics in very premature infants treated with poractant alfa or beractant for respiratory distress syndrome. J Perinatol. 2010 Oct;30(10):671-6. doi: 10.1038/jp.2010.21. Epub 2010 Mar 25.
citation: Fujii AM, Bailey J, Doros G, Sampat K, Sikes NC, Mason M, Kaiser JR. Cerebral Blood Flow Responses to Beractant and Poractant Administration. Journal of Neonatal-Perinatal Medicine 2009; 2:27-34