Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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
Results First Received: April 27, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Prematurity
Respiratory Distress Syndrome
Patent Ductus Arteriosus
Interventions: Drug: Survanta (beractant)
Drug: Curosurf (poractant)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients born between 1/2005 and 5/2008 with respiratory distress syndrome requiring mechanical ventilation, <30 weeks gestation, greater than 500 g and whose parents provided informed consent were included in the study. Infants with multiple congenital anomalies, significant congenital heart disease were excluded.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Participant Flow:   Overall Study
    Beractant Arm     Poractant Alfa Arm  
STARTED     27 [1]   25  
COMPLETED     22     23  
NOT COMPLETED     5     2  
Death                 5                 2  
[1] Two early deaths and 3 late deaths occurred in this group



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)
Total Total of all reporting groups

Baseline Measures
    Beractant Arm     Poractant Alfa Arm     Total  
Number of Participants  
[units: participants]
  27     25     52  
Age [1]
[units: years]
     
<=18 years     27     25     52  
Between 18 and 65 years     0     0     0  
>=65 years     0     0     0  
Gender  
[units: participants]
     
Female     7     13     20  
Male     20     12     32  
Region of Enrollment  
[units: participants]
     
United States     27     25     52  
Gestational Age in weeks [2]
[units: weeks]
Mean ± Standard Deviation
  26.7  ± 1.7     27.1  ± 1.6     26.9  ± 1.6  
[1] The population is recruited from premature infants with Respiratory Distress Syndrome on the first day of life.
[2] All patients are enrolled on the first day of life. Therefore the mean +/- SD = 0 +/- 0 years.



  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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 ]

Measure Type Primary
Measure Title Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
Measure Description 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.
Time Frame 48 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled subjects surviving >/= 3 days were included in the analysis. Two subjects in the Survanta (beractant) groups died in this period and were eliminated from this portion of the analysis.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  25     25  
Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.  
[units: cm H20]
Mean ± Standard Error
  8.6  ± 0.8     6.4  ± 0.4  


Statistical Analysis 1 for Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] < 0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Respiratory support were compared using a t-test for individual time points and Generalized Linear Model to account for correlations among repeated measures. Patient who survive >/= 3 days were included in the analysis.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Tested null hypothesis. T-test and Generalized Linear Model was used to assess respiratory support parameters (mean airway pressure and percent fraction of inspiratory oxygen x mean airway pressure).



2.  Primary:   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 ]

Measure Type Primary
Measure Title Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration
Measure Description 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.
Time Frame 72 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled subjects surviving >/= 3 days were included in the analysis. Two subjects in the Survanta (beractant) groups died in this period and were eliminated from this portion of the analysis.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  25     25  
Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration  
[units: cm H20]
Mean ± Standard Error
  7.9  ± 0.6     6.0  ± 0.7  


Statistical Analysis 1 for Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] <0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Tested null hypothesis. T-test and Generalized Linear Model was used to assess respiratory support parameters (mean airway pressure and percent fraction of inspiratory oxygen x mean airway pressure).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



3.  Primary:   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 ]

Measure Type Primary
Measure Title Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
Measure Description 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.
Time Frame 48 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled subjects surviving >/= 3 days were included in the analysis. Two subjects in the Survanta (beractant) groups died in this period and were eliminated from this portion of the analysis.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  25     25  
Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.  
[units: cm H20-Percent of O2]
Mean ± Standard Error
  274  ± 35     170  ± 18  


Statistical Analysis 1 for Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] <0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Tested null hypothesis. T-test and Generalized Linear Model was used to assess respiratory support parameters (mean airway pressure and percent fraction of inspiratory oxygen x mean airway pressure).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  Primary:   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 ]

Measure Type Primary
Measure Title Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration.
Measure Description 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.
Time Frame 72 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Enrolled subjects surviving >/= 3 days were included in the analysis. Two subjects in the Survanta (beractant) groups died in this period and were eliminated from this portion of the analysis.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  25     25  
Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration.  
[units: cm H20-Percent of O2]
Mean ± Standard Error
  226  ± 29     140  ± 16  


Statistical Analysis 1 for Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration.
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] <0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Tested null hypothesis. T-test and Generalized Linear Model was used to assess respiratory support parameters (mean airway pressure and percent fraction of inspiratory oxygen x mean airway pressure).
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



5.  Secondary:   Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups   [ Time Frame: 48 hours after surfactant administration ]

Measure Type Secondary
Measure Title Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
Measure Description 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.
Time Frame 48 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients no longer needing positive pressure endotracheal mechanical ventilation were tallied to help explain the between group differences in mean airway pressure.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  27     25  
Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups  
[units: Participants successfully extubated]
Number ( 90% Confidence Interval )
  6  
  ( 3 to 10 )  
  13  
  ( 9 to 17 )  


Statistical Analysis 1 for Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] <0.05
Risk Ratio (RR) [4] 0.43
95% Confidence Interval ( 0.19 to 0.95 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



6.  Secondary:   Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups   [ Time Frame: 72 hours after surfactant administration ]

Measure Type Secondary
Measure Title Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
Measure Description 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.
Time Frame 72 hours after surfactant administration  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients no longer needing positive pressure endotracheal mechanical ventilation were tallied to help explain the between group differences in mean airway pressure.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  27     25  
Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups  
[units: Participants successfully extubated]
Number ( 90% Confidence Interval )
  8  
  ( 5 to 12 )  
  15  
  ( 11 to 19 )  


Statistical Analysis 1 for Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] <0.05
Risk Ratio (RR) [4] 0.49
95% Confidence Interval ( 0.25 to 0.96 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   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 ]

Measure Type Secondary
Measure Title Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)
Measure Description 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.
Time Frame Hemodynamically significant PDA at > 2 days  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with clinically and hemodynamically significant Patent Ductus Arteriosus, on evaluation at >3 days, were tallied

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  25     25  
Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)  
[units: Subjects]
Number ( 90% Confidence Interval )
  19  
  ( 15 to 22 )  
  8  
  ( 5 to 12 )  


Statistical Analysis 1 for Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] <0.01
Risk Ratio (RR) [4] 2.38
95% Confidence Interval ( 1.29 to 4.38 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



8.  Secondary:   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 ]

Measure Type Secondary
Measure Title Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)
Measure Description 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.
Time Frame First hour after 2nd surfactant dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population was limited to those subjects with PDA's who were treated with a second dose of surfactant, when the subjects were hemodynamically stable enough to yield meaning data.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  9     7  
Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)  
[units: cc/min]
Mean ± Standard Error
   
Baseline PDA Flow, before surfactant (cc/min)     138  ± 36     123  ± 45  
Maximal PDA Flow, following surfactant (cc/min)     169  ± 52     143  ± 35  
Change in PDA Flow, following surfactant (cc/min)     32  ± 42     20  ± 37  


Statistical Analysis 1 for Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] >0.05
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



9.  Secondary:   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 ]

Measure Type Secondary
Measure Title Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant
Measure Description 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.
Time Frame One hour following second surfactant dose at 12-24 hours after initial dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The population analyzed was limited to subjects that received second dose of surfactant and were clinically stable enough to allow Doppler assessment of cerebral blood flow during the first hour following surfactant administration.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  9     7  
Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant  
[units: Percent change from baseline velocity]
Mean ± Standard Error
   
Blood Flow Velocity, before surfactant (cm/sec)     12.5  ± 1.5     22.4  ± 2.8  
Peak Blood Flow Velocity, post surfactant (cm/sec)     18.3  ± 2.4     20.4  ± 2.1  
Peak Change in Blood Flow Velocity (cm/sec)     5.6  ± 1.3     -2.0  ± 3.1  
Percent Change in Blood Flow Velocity (%)     47.4  ± 11.9     -1.8  ± 14.6  


Statistical Analysis 1 for Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant
Groups [1] All groups
Method [2] t-test, 2 sided
P Value [3] <0.01
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



10.  Secondary:   Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)   [ Time Frame: 36 weeks post menstrual age ]

Measure Type Secondary
Measure Title Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)
Measure Description 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.
Time Frame 36 weeks post menstrual age  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Population analyzed was limited to those subjects who survived to >36 weeks post menstrual age. Subjects with Bronchopulmonary Dysplasia (continuous supplemental oxygen need at >36 weeks post menstrual age) were tallied.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  22     23  
Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)  
[units: Surviving Subjects with BPD]
Number ( 90% Confidence Interval )
  11  
  ( 7 to 15 )  
  8  
  ( 4 to 11 )  


Statistical Analysis 1 for Patients With Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age)
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] >0.05
Risk Ratio (RR) [4] 1.44
95% Confidence Interval ( 0.71 to 2.89 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.



11.  Secondary:   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 ]

Measure Type Secondary
Measure Title Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU.
Measure Description 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.
Time Frame NICU hospitalization, up to 42 weeks post menstrual age  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All subjects enrolled were included. Subjects with Bronchopulmonary Dysplasia (continuous supplemental oxygen need at > 36 weeks post menstrual age) and patients who expired before discharge from the NICU were tallied.

Reporting Groups
  Description
Beractant Arm Surfactant (beractant, Survanta), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (100 mg/kg initial and subsequent doses, up to 4 doses at 6-12 h intervals)
Poractant Alfa Arm Surfactant (poractant, Curosurf), intratracheal administration to very premature infants with RDS requiring mechanical ventilation (initial dose 200 mg/kg, subsequent doses 100 mg/kg, up to 3 doses)

Measured Values
    Beractant Arm     Poractant Alfa Arm  
Number of Participants Analyzed  
[units: participants]
  27     25  
Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU.  
[units: Subjects with BPD + Neonatal Deaths]
Number ( 90% Confidence Interval )
  16  
  ( 12 to 20 )  
  10  
  ( 6 to 14 )  


Statistical Analysis 1 for Bronchopulmonary Dysplasia (Supplemental Oxygen at 36 Week Post Menstrual Age) or Death Before Discharge From NICU.
Groups [1] All groups
Method [2] Mantel Haenszel
P Value [3] >0.05
Risk Ratio (RR) [4] 1.48
90% Confidence Interval ( 0.84 to 2.63 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The primary limitations are the small number of patients, the high rate of chronic lung disease in the beractant group and the open-label design of the study.


  More Information