For children undergoing bone marrow transplantation, respiratory failure is a devastating complication, with mortality expectations well above 60%. The researchers have devised a novel strategy that may greatly improve survival. Hemofiltration, a continuous form of dialysis, was designed as a therapy for critically ill patients with kidney failure. A semi-permeable membrane removes plasma water and solutes (up to about 35,000 Daltons molecular weight). The researchers have treated immuno-compromised children with respiratory failure with hemofiltration. Many inflammatory molecules are of a size well below the limit of the filter. Hemofiltration might remove a critical amount of this inflammatory material, attenuating the unregulated inflammatory response that is central to the development of respiratory failure and progression to multiple organ failure and death. The researchers are conducting a multi-center trial of early continuous hemofiltration for respiratory failure in children following bone marrow transplantation. The researchers will analyze blood and ultrafiltrate using sensitive proteomic methods to detect several inflammatory biochemicals known to be active in this disease, looking for evidence that early active hemofiltration alters the inflammatory response. The researchers will test whether `early` hemofiltration produces greater survival from respiratory failure in this vulnerable population.

Condition	Intervention	Phase
Bone Marrow Transplantation Respiratory Insufficiency	Procedure: hemofiltration	Phase II Phase III

Further Study Details: 

Primary Outcomes: Survival
Secondary Outcomes: PELOD organ failure score; number of ventilator-free days; duration of hospitalization; functional outcome score
Expected Total Enrollment:  112

For children undergoing bone marrow transplantation, respiratory failure carries mortality expectations well above 60%. The researchers have published preliminary evidence that continuous hemofiltration may greatly improve survival, if filtration is begun when the child first fulfills clinical criteria for ARDS. This is a departure from standard practice, as hemofiltration is usually begun later in the course (if at all) when multiple organ failure is entrenched. Hemofiltration, a `renal replacement therapy` for critically ill patients, is a slow, continuous process in which a semi-permeable membrane removes plasma water and solutes (up to about 35 kiloDaltons). Many cytokine and chemokine molecules are smaller than the molecular weight limit of the filter; hemofiltration might remove a critical amount, attenuating the unregulated inflammatory response responsible for respiratory failure and progression to multiple organ failure and death. The researchers will conduct a multi-center randomized trial assessing the effect of hemofiltration on survival from respiratory after bone marrow (or more precisely, hematopoietic stem cell) transplantation. The researchers will perform sensitive proteomic assays of serum and ultrafiltrate, to detect the presence of cytokines and chemokines known to be active in idiopathic pneumonia syndrome. Resulting profiles will constitute a uniquely complex description of ultrafiltrate and may provide evidence for modulation of immune function by hemofiltration.

Ages Eligible for Study:  1 Month   -   21 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• hematopoietic stem cell recipient
• respiratory failure fulfilling ARDS criteria
• mechanical ventilation (invasive / non-invasive)

Exclusion Criteria:

• extracorporeal membrane oxygenation (ECMO)
• predominance of congestive heart failure
• code status: a patient must be willing to accept invasive mechanical ventilation if clinically indicated

Please refer to this study by ClinicalTrials.gov identifier  NCT00120575

Joseph V DiCarlo, MD      (650) 497-8850    jdicarlo@stanford.edu

California
      Children''''s Hospital and Research Center, Oakland,  California,  94609,  United States; Not yet recruiting
Georgia
      Children''''s Healthcare of Atlanta @ Egleston, Atlanta,  Georgia,  30322,  United States; Recruiting
North Carolina
      Duke University, Durham,  North Carolina,  27710,  United States; Recruiting
Pennsylvania
      Children''''s Hospital of Philadelphia, Philadelphia,  Pennsylvania,  19104,  United States; Not yet recruiting
Canada, British Columbia
      Children''''s Hospital of British Columbia, Vancouver,  British Columbia,  Canada; Not yet recruiting
Germany
      University of Ulm, Ulm,  Germany; Recruiting
United Kingdom
      Great Ormond Street Hospital, London,  United Kingdom; Recruiting

Study chairs or principal investigators

Joseph V DiCarlo, MD,  Principal Investigator,  Stanford University   

Study ID Numbers:  BMT CVVH
Record last reviewed:  July 2005
Last Updated:  July 25, 2005
Record first received:  July 15, 2005
ClinicalTrials.gov Identifier:  NCT00120575
Health Authority: United States: Institutional Review Board
ClinicalTrials.gov processed this record on 2005-07-26