Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants

This study has been terminated.
(Slow recruitment,changes in protocols, larger than anticipated differences)
Sponsor:
Collaborator:
Dey LP
Information provided by (Responsible Party):
Alan Fujii, Boston Medical Center
ClinicalTrials.gov Identifier:
NCT00767039
First received: December 17, 2007
Last updated: September 28, 2011
Last verified: October 2008

December 17, 2007
September 28, 2011
January 2005
September 2008   (final data collection date for primary outcome measure)
  • Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration. [ Time Frame: 48 hours after surfactant administration ] [ Designated as safety issue: No ]
    Mean Airway Pressure delivered by mechanical ventilator or nasal CPAP (cm H20) at 48 hours following surfactant administration. A volume cycle ventilator strategy that allowed airway pressure to vary with changes in lung and chest wall compliance was used for mechanically ventilated infants, while inspired oxygen concentration was controlled by the clinical team.
  • Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration [ Time Frame: 72 hours after surfactant administration ] [ Designated as safety issue: No ]
    Mean Airway Pressure delivered by mechanical ventilator or nasal CPAP (cm H20) at 72 hours following surfactant administration. A volume cycle ventilator strategy that allowed airway pressure to vary with changes in lung and chest wall compliance was used for mechanically ventilated infants, while oxygen concentration was controlled by the clinical team.
  • Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration. [ Time Frame: 48 hours after surfactant administration ] [ Designated as safety issue: No ]
    Mean Airway Pressure x Percent Fraction of Inspired Oxygen (FIO2) at 48 hours after surfactant administration, delivered by mechanical ventilator or nasal CPAP assesses the components of respiratory support primarily affecting blood oxygenation. This index combines these parameters so that a systematic difference in clinical management of mean airway pressure or FIO2 between groups is not mistaken for a drug effect.
  • Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration. [ Time Frame: 72 hours after surfactant administration ] [ Designated as safety issue: No ]
    Mean Airway Pressure x Percent Fraction of Inspired Oxygen (FIO2) at 72 hours after surfactant administration, delivered by mechanical ventilator or nasal CPAP assesses the components of respiratory support primarily affecting blood oxygenation. This index combines these parameters so that a systematic difference in clinical management of mean airway pressure or FIO2 between groups is not mistaken for a drug effect.
Comparison of the respiratory support index (FIO2, mean airway pressure, respiratory index, oxygenation index) for Curosurf and Survanta over the first 3 days of life. [ Time Frame: 3 days after surfactant administration ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00767039 on ClinicalTrials.gov Archive Site
  • Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups [ Time Frame: 48 hours after surfactant administration ] [ Designated as safety issue: No ]
    Subjects successfully extubated and no longer needing positive pressure endotracheal mechanical ventilation at 48 hours after surfactant administration helps to explain the difference in mean airway pressure observed between groups.
  • Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups [ Time Frame: 72 hours after surfactant administration ] [ Designated as safety issue: No ]
    Subjects successfully extubated and no longer needing positive pressure endotracheal mechanical ventilation at 72 hours after surfactant administration helps to explain the difference in mean airway pressure observed between groups.
  • Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant) [ Time Frame: Hemodynamically significant PDA at > 2 days ] [ Designated as safety issue: No ]
    Hemodynamically significant PDA, considered significant by the clinical team and having at least 2 objective echocardiographic signs (PDA > 1.5 mm diameter, retrograde diastolic flow in the descending aorta, and left atrial enlargement) were tallied. Hemodynamically significant PDA may increase lung water and decrease lung compliance, requiring increased mechanical ventilator support.
  • Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf) [ Time Frame: First hour after 2nd surfactant dose ] [ Designated as safety issue: No ]
    Maximal changes in blood flow were assessed using Doppler echocardiography following the second surfactant dose of Survanta (beractant) or Curosurf (poractant alfa), to determine whether there was a direct effect of surfactant type on PDA size or pulmonary volume overload through the PDA. The hour interval following the second surfactant dose was selected for study, when the subjects were otherwise clinically stable, not needing additional stabilization procedures.
  • Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant [ Time Frame: One hour following second surfactant dose at 12-24 hours after initial dose ] [ Designated as safety issue: No ]
    Percent change in Anterior Cerebral Artery blood flow velocity following the second dose of beractant, reflects the change in brain blood flow associated with surfactant administration. Blood flow velocity is measured by range gated Doppler ultrasound and brain blood flow changes in proportion to changes in arterial carbon dioxide levels, induced by surfactant administration. Variability in brain blood flow is associated with increased risk for intraventricular hemorrhage.
  • Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) [ Time Frame: 36 weeks post menstrual age ] [ Designated as safety issue: No ]
    Patients with Bronchopulmonary Dysplasia (BPD), had chronic lung disease requiring supplemental oxygen support at >/= 36 weeks post menstrual age, were tallied. BPD is a chronic lung disease that develops, at least in part, as a consequence of NICU respiratory management of premature infants with Respiratory Distress Syndrome.
  • Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU. [ Time Frame: NICU hospitalization, up to 42 weeks post menstrual age ] [ Designated as safety issue: No ]
    Bronchopulmonary Dysplasia + death outcome for all patients enrolled in the study were tallied and used to determine whether neonatal death decreased the frequency of chronic lung disease in one group vs the other.
  • Organ blood flow responses to Curosurf and Survanta, to brain, through the Patent Ductus Arteriosus and superior mesenteric artery [ Time Frame: First hour after surfactant adminsitration ] [ Designated as safety issue: No ]
  • Chronic lung disease or death [ Time Frame: duration of NICU stay ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Curosurf and Survanta Treatment(CAST)of RDS in Very Premature Infants
Phase 4 Study of Curosurf (Poractant) and Survanta (Beractant) Surfactant Treatment in Very Premature Infants With Respiratory Distress Syndrome.

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prematurity
  • Respiratory Distress Syndrome
  • Patent Ductus Arteriosus
  • Drug: Survanta (beractant)
    beractant 4.0 ml/kg/dose (100 mg phospholipid/kg/dose, intratracheal, every 6-12 hours as needed for respiratory distress syndrome for initial and subsequent doses, maximum of 4 doses)
    Other Name: Survanta
  • Drug: Curosurf (poractant)
    poractant alfa 2.5 ml/kg/dose initial (200 mg phospholipid/kg), and 1.25 ml/kg/dose subsequent (100 mg/kg/subsequent dose), intratracheal, every 12-24 hours as needed for respiratory distress syndrome, maximum of 3 doses)
    Other Name: Curosurf
  • Active Comparator: 1
    Surfactant (beractant, Survanta initial dose 100 mg/kg and subsequent doses 100 mg/kg phospholipids every 6-12 hours, as needed for up to 4 doses), intratracheal administration to very premature infants with RDS requiring mechanical ventilation
    Intervention: Drug: Survanta (beractant)
  • Experimental: 2
    Surfactant (poractant, Curosurf initial dose 200 mg/kg and subsequent doses 100 mg/kg phospholipids every 12-24 hours as needed for up to 3 doses), intratracheal administration to very premature infants with RDS requiring mechanical ventilation
    Intervention: Drug: Curosurf (poractant)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
52
January 2009
September 2008   (final data collection date for primary outcome measure)

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
Both
up to 8 Hours
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00767039
H-23371
No
Alan Fujii, Boston Medical Center
Alan Fujii
Dey LP
Principal Investigator: Alan M Fujii, MD Boston Medical Center
Boston Medical Center
October 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP