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

Acute Lung Injury Clinical Trial

— CALIPSO  

Official title:

A Phase 3 Trial of Calfactant for ALI in Pediatric Leukemia and HSCT Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00999713
• Other study ID #: 1R01FD003410-01
• Secondary ID: R01FD003410-01A1
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 18, 2009
• Last updated: February 15, 2018
• Start date: June 2010
• Est. completion date: October 2015

Study information

• Verified date: February 2018
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: October 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 21 Years

Eligibility

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).

Related Conditions & MeSH terms

• Acute Lung Injury
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Wounds and Injuries

Intervention

Drug:
• Calfactant
Endotracheal calfactant, up to 3 doses if subject qualifies

Other:
• Air placebo
Endotracheal air administration

Locations

Country	Name	City	State
Canada	Hospital Sainte Justine	Montreal	Quebec
United States	Rainbow Babies Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Texas Children's Hospital	Houston	Texas
United States	Riley Children's Hospital	Indianapolis	Indiana
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Weill Cornell Medical Center	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Maria Fareri Children's Hospital	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (2)

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. — View 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. Erratum in: JAMA. 2005 Aug 24;294(8):900. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality at the Time of Pediatric Intensive Care Unit (PICU) Discharge	Overall mortality rate from admission to PICU discharge	Admission to PICU discharge, up to 120 days
Secondary	Ventilator Free Days (VFDs)	Number of days the patient is alive and off of the ventilator	60 days after study enrollment
Secondary	Total Duration of Stay Required	Length of stay (LOS) ,measured in days, from admission to PICU discharge and admission to hospital discharge.	Admission to discharge, up to 120 days
Secondary	Change in Oxygenation: First Intervention	The Oxygenation Index after the first intervention is calculated as the fraction of inspired oxygen, in percent, times the mean airway pressure, in mmHg, divided by the partial pressure of oxygen in arterial blood, in mmHg. Lower values are better.	48 hours after enrollment, up to 12 hours after each intervention
Secondary	Change in Oxygenation: Second Intervention	The Oxygenation Index after the second intervention (if applicable) is calculated as the fraction of inspired oxygen, in percent, times the mean airway pressure, in mmHg, divided by the partial pressure of oxygen in arterial blood, in mmHg. Lower values are better.	48 hours after enrollment, up to 12 hours after each intervention