CALIPSO: Calfactant for Acute Lung Injury in Pediatric Stem Cell Transplant and Oncology Patients

• Total duration of mechanical ventilation required during PICU admission. [ Time Frame: PICU discharge ] [ Designated as safety issue: No ]
• Total duration of PICU and hospital stay required. [ Time Frame: Hospital discharge ] [ Designated as safety issue: No ]
• Improvement in oxygenation, as measured by oxygenation index, in the initial 48 hours after treatment [ Time Frame: 48 hours after enrollment ] [ Designated as safety issue: No ]

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.

• Drug: Calfactant
  Endotracheal calfactant, up to 3 doses if subject qualifies
• Other: Air placebo
  Endotracheal air administration

• Experimental: Calfactant
  Endotracheal calfactant administration
  Intervention: Drug: Calfactant
• Placebo Comparator: Placebo (air)
  Endotracheal air administration
  Intervention: Other: Air placebo

• 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.
• 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. Erratum in: JAMA. 2005 Aug 24;294(8):900.

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 mEq/L for more than 2 hours,
   • persistent arterial oxygen desaturation, PaO2 < 50 or SaO2saturation < 80%,
   • hyperkalemia, serum K+ > 6.5 plus widening of QRS complex on EKG