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

NCT00767039 | Terminated Phase 4 Results

• 1 other identifier: H-23371
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Prematurity; Respiratory Distress Syndrome; Patent Ductus Arteriosus

Keywords

Very Premature; RDS; Surfactant

Outcome Measures

Primary Outcomes (4)

• Comparison Respiratory Support (Mean Airway Pressure) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.

  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.

  48 hours after surfactant administration

• Comparison of Respiratory Support (Mean Airway Pressure) for Curosurf (Poractant) and Survanta (Beractant) 72 Hours After Surfactant Administration

  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.

  72 hours after surfactant administration

• Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 48 Hours After Surfactant Administration.

  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.

  48 hours after surfactant administration

• Comparison Respiratory Support (Mean Airway Pressure x Percent Fraction of Inspired Oxygen) for Survanta (Beractant) and Curosurf (Poractant) at 72 Hours After Surfactant Administration.

  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.

  72 hours after surfactant administration

Secondary Outcomes (7)

• Comparison of Infants Successfully Extubated at 48 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups

  48 hours after surfactant administration

• Comparison of Infants Successfully Extubated at 72 Hours for Curosurf (Poractant) and Survanta (Beractant) Groups

  72 hours after surfactant administration

• Comparison of Hemodynamically Significant Patent Ductus Arteriosus (PDA) in Patients Treated With Curosurf (Poractant) and Survanta (Beractant)

  Hemodynamically significant PDA at > 2 days

• Changes in Blood Flow Through the Patent Ductus Arteriosus (PDA) Following Second Dose of Survanta (Beractant) and Poractant Alfa (Curosurf)

  First hour after 2nd surfactant dose

• Change in Anterior Cerebral Artery Blood Flow Velocity Following Second Dose of Surfactant

  One hour following second surfactant dose at 12-24 hours after initial dose

Study Arms (2)

1

ACTIVE COMPARATOR

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

Drug: Survanta (beractant)

2

EXPERIMENTAL

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

Drug: Curosurf (poractant)

Interventions

Survanta (beractant) DRUG

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)

Also known as: Survanta

1

Curosurf (poractant) DRUG

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)

Also known as: Curosurf

2

Eligibility Criteria

• Age: Up to 8 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \<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)

You may not qualify if:

• \<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

Sponsors & Collaborators

• Alan Fujii: lead
• Dey LP: collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (6)

• Fujii AM, Editorial. Is There Really A Clinical Difference In Surfactant Preparations? J Perinatol 2010; 30:698; doi:10,1038/jp.2010.90

  BACKGROUND

• Fujii A. Editorial. Are all animal derived surfactants the same? The e-NeoResearch 2011; 1 (1); 50-51.

  BACKGROUND

• 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. doi: 10.1358/dot.2009.45.9.1418185.

  PMID: 19956811 RESULT

• 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.

  PMID: 20336076 RESULT

• 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.

  PMID: 20336077 RESULT

• 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

  RESULT

MeSH Terms

Conditions

Premature Birth; Respiratory Distress Syndrome; Ductus Arteriosus, Patent

Interventions

beractant; poractant alfa

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

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.

Results Point of Contact

• Title: Alan Fujii MD (PI)
• Organization: Boston Medical Center

Alan.Fujii@bmc.org

617-4414-3735

Study Officials

• Alan M Fujii, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 17, 2007
• First Posted: October 6, 2008
• Study Start: January 1, 2005
• Primary Completion: September 1, 2008
• Study Completion: January 1, 2009
• Last Updated: October 3, 2011
• Results First Posted: September 20, 2011

Record last verified: 2008-10

Locations

US (1)