Hemofiltration for Respiratory Failure After Bone Marrow Transplantation

NCT ID: NCT00120575

Last Updated: 2006-12-05

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-01-31
• Study Completion Date: 2008-09-30

Brief Summary

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.

Detailed Description

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.

Conditions

Bone Marrow Transplantation; Respiratory Insufficiency

Keywords

Hemofiltration; Pediatrics

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

hemofiltration

Intervention Type: PROCEDURE

Eligibility 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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Principal Investigators

Joseph V DiCarlo, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Children's Hospital and Research Center

Oakland, California, United States

Site Status: NOT_YET_RECRUITING

Children's Healthcare of Atlanta @ Egleston

Atlanta, Georgia, United States

Site Status: RECRUITING

Duke University

Durham, North Carolina, United States

Site Status: RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status: NOT_YET_RECRUITING

Children's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status: NOT_YET_RECRUITING

University of Ulm

Ulm, , Germany

Site Status: RECRUITING

Great Ormond Street Hospital

London, , United Kingdom

Site Status: RECRUITING

Countries

United States; Canada; Germany; United Kingdom

Central Contacts

Joseph V DiCarlo, MD

Role: CONTACT

Phone: (650) 497-8850

Email: jdicarlo@stanford.edu

Facility Contacts

Vivienne Newman, MD

Role: primary

James Fortenberry, MD

Role: primary

Ira Cheifetz, MD

Role: primary

Vinay Nadkarni, MD

Role: primary

Peter Skippen, MD

Role: primary

Gordon Krahn

Role: backup

Helmut Hummler, MD

Role: primary

Quen Mok, MB BS

Role: primary

References

DiCarlo JV, Alexander SR, Agarwal R, Schiffman JD. Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy. J Pediatr Hematol Oncol. 2003 Oct;25(10):801-5. doi: 10.1097/00043426-200310000-00012.

Reference Type: BACKGROUND

PMID: 14528104 (View on PubMed)

Di Carlo JV, Alexander SR. Hemofiltration for cytokine-driven illnesses: the mediator delivery hypothesis. Int J Artif Organs. 2005 Aug;28(8):777-86. doi: 10.1177/039139880502800803.

Reference Type: BACKGROUND

PMID: 16211527 (View on PubMed)

Other Identifiers

BMT CVVH

Identifier Type: -

Identifier Source: org_study_id