CALIPSO: A Randomized Controlled Trial of Calfactant for Acute Lung Injury in Pediatric Stem Cell and Oncology Patients
OBJECTIVE: To assess if calfactant reduces mortality among children with leukemia/lymphoma or following hematopoietic cell transplantation (HCT) with pediatric acute respiratory distress syndrome (PARDS) DESIGN: Multicenter, randomized, placebo-controlled, double-blinded trial SETTING: Seventeen pediatric intensive care units (PICU) of tertiary care children's hospitals PATIENTS: Patients age 18 months to 25 years with leukemia/lymphoma or having undergone HCT who required invasive mechanical ventilation for bilateral lung disease with an oxygenation index (OI) >10 and < 37. INTERVENTIONS: Intratracheal instillation of either calfactant or air placebo (one or two doses) MEASUREMENTS AND MAIN RESULTS: Forty-three subjects were enrolled between November, 2010 and June 2015; 26 assigned to calfactant and 17 to placebo. There were no significant differences in the primary outcome, which was survival to PICU discharge (Adjusted Hazard Ratio of mortality for calfactant vs. placebo (95% CI): 1.78 (0.53, 6.05); p=0.35), OI, functional outcomes, or ventilator free days, adjusting for risk strata and PRISM score. Despite the risk-stratified randomization, more allogeneic HCT patients received calfactant (76% and 39%, respectively) due to low recruitment at various sites. This imbalance is important because, independent of treatment arm, and while adjusting for PRISM score, those with allogeneic HCT had a non-significant higher likelihood of death at PICU discharge (Adjusted Odds Ratio (95% CI): 3.02 (0.76, 12.06); p=0.12). Overall, 86% of the patients who survived to PICU discharge also were successfully discharged from the hospital. CONCLUSIONS: These data do not support the use of calfactant among this high mortality group of pediatric leukemia/lymphoma and/or HCT patients with PARDS to increase survival. In spite of poor enrollment, allogeneic HCT patients with PARDS appeared to be characterized by higher mortality than even other high-risk immunosuppressed groups. Conducting research among these children is challenging but necessary, as survival to PICU discharge usually results in successful discharge to home.
Thomas, N., Spear, D., Wasserman, E., Pon, S., Markovitz, B., Singh, A., Li, S., Gertz, S., Rowan, C., Kunselman, A., Tamburro, R., & CALIPSO Study Investigators and the Pediatric Acute Lung Injury and Sepsis Investigators Network. (2018). CALIPSO: A Randomized Controlled Trial of Calfactant for Acute Lung Injury in Pediatric Stem Cell and Oncology Patients. Biology of Blood and Marrow Transplantation, 24 (12), 2479-2486. https://doi.org/10.1016/j.bbmt.2018.07.023