Clinical trial NCT00999713: CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients
Official title: A Phase 3 Trial of Calfactant for ALI in Pediatric Leukemia and HSCT Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Lung Injury
Keywords: Acute Lung Injury
Cancer
Pediatrics
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2009-10-22
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute lung injury (ALI) is a common, life-threatening complication among pediatric leukemia and lymphoma and hematopoietic stem cell transplant (HSCT) recipients. Although these children represent a relatively small and unique patient population, they account for the largest proportion of deaths of all pediatric diseases. The long-term goal of this project is to improve outcomes among these patients. Recently, the intratracheal administration of calfactant has resulted in decreased mortality among children with ALI including promising results among children with cancer and following HSCT. Consequently, the primary specific aim of this study is to assess the effect of calfactant on intensive care (PICU) survival among pediatric leukemia and lymphoma and HSCT patients with ALI. Secondary aims include assessment of the effect of calfactant on oxygenation and on the length of mechanical ventilation, PICU stay, and hospital stay. Calfactant therapy has been found to be of benefit in acute lung injury in the overall pediatric population by improving oxygenation and decreasing mortality. These findings, in conjunction with recent subgroup analysis in which calfactant therapy appeared to improve outcomes in immunocompromised children provide the rationale for assessing calfactant therapy in this patient population.

Funding Source - FDA Office of Orphan Products Development (OOPD)


Eligibility criteria: Inclusion Criteria:

1. Patients must meet criteria for acute lung injury

   * Intubated, mechanically ventilated, with respiratory failure secondary to diffuse, bilateral parenchymal lung disease (as judged by chest x-ray).
   * Oxygenation index (OI) \> 13, but \< 37, for two consecutive blood gases which should be separated by at least one hour within 48 hours of the initiation of mechanical ventilation.
   * Arterial catheter placement
   * Parental informed consent
2. Patients must have a diagnosis of leukemia/lymphoma undergoing active treatment or following HSCT for any indication. Leukemia/lymphoma will be defined according to the National Cancer Institute Surveillance Epidemiology and End Results Collaborative Staging Manual including those conditions defined as borderline such as myelodysplastic syndromes. All forms of HSCT will be eligible, allogeneic as well as autologous.

Exclusion Criteria:

1. Clinical diagnosis of congestive heart failure and/or pulmonary capillary wedge pressure \>15 mmHg, or uncorrected congenital heart disease.
2. Glasgow Coma Score \< 8 (prior to respiratory failure).
3. Pre-existing limitations on care options, (Do Not Attempt Resuscitation Orders, etc).
4. Patients with impending death from another disease.
5. Patients moribund or with other organ failure at possible randomization:

   * hypotension unresponsive to treatment (mean BP \< 60 or \< 5th % for age),
   * persistent cardiac tachyarrhythmia \>150/minute, or persistent bradyarrythmia \< 50/minute, or age appropriate criteria for younger children,
   * metabolic acidosis \> - 10 milliequivalent (mEq)/L for more than 2 hours,
   * persistent arterial oxygen desaturation, arterial partial pressure of oxygen (PaO2) \< 50 or oxygen saturation (SaO2) saturation \< 80%,
   * hyperkalemia, serum K+ \> 6.5 plus widening of QRS complex on EKG (QRS complex corresponds to the depolarization of the right and left ventricles of the heart).

Primary outcomes:
measure: All-cause Mortality at the Time of Pediatric Intensive Care Unit (PICU) Discharge
timeFrame: Admission to PICU discharge, up to 120 days
Secondary outcomes:
measure: Ventilator Free Days (VFDs)
timeFrame: 60 days after study enrollment
measure: Total Duration of Stay Required
timeFrame: Admission to discharge, up to 120 days
measure: Change in Oxygenation: First Intervention
timeFrame: 48 hours after enrollment, up to 12 hours after each intervention
measure: Change in Oxygenation: Second Intervention
timeFrame: 48 hours after enrollment, up to 12 hours after each intervention
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Indianapolis
country: United States
facility: Riley Children's Hospital
state: Indiana
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medical Center
state: New York
city: Valhalla
country: United States
facility: Maria Fareri Children's Hospital
state: New York
city: Cleveland
country: United States
facility: Rainbow Babies Hospital
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Montreal
country: Canada
facility: Hospital Sainte Justine
state: Quebec
Study officials:
affiliation: Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
name: Neal J Thomas, MD, MSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State College of Medicine, Penn State Milton S. Hershey Medical Center
name: Robert F Tamburro, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tamburro RF, Thomas NJ, Pon S, Jacobs BR, Dicarlo JV, Markovitz BP, Jefferson LS, Willson DF; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials. Pediatr Crit Care Med. 2008 Sep;9(5):459-64. doi: 10.1097/PCC.0b013e3181849bec.
citation: Willson DF, Thomas NJ, Markovitz BP, Bauman LA, DiCarlo JV, Pon S, Jacobs BR, Jefferson LS, Conaway MR, Egan EA; Pediatric Acute Lung Injury and Sepsis Investigators. Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial. JAMA. 2005 Jan 26;293(4):470-6. doi: 10.1001/jama.293.4.470.