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The BOLD Study B eta-agonists for O xygenation in L ung D onors

The BOLD Study B eta-agonists for O xygenation in L ung D onors. Background. Demand for donor lungs exceeds the available supply Donor hypoxemia and radiographic infiltrates are common reasons for rejection of lungs for transplantation

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The BOLD Study B eta-agonists for O xygenation in L ung D onors

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  1. The BOLD StudyBeta-agonists for Oxygenation in Lung Donors

  2. Background • Demand for donor lungs exceeds the available supply • Donor hypoxemia and radiographic infiltrates are common reasons for rejection of lungs for transplantation • Pulmonary edema is a common cause of hypoxemia and pulmonary infiltrates in brain dead organ donors

  3. The majority of organ donors have some degree of pulmonary edema Mean Wet to Dry Ratio 4.4 ± 0.6 in 29 organ donors whose lungs were rejected for transplantation Lancet 2002; 360: 619-20

  4. Alveolar fluid clearance is intact in the majority of lungs rejected for transplantation Mean Alveolar Fluid Clearance 4.7 ± 2.4 %/h Lancet 2002; 360: 619-20

  5. A beta-adrenergic agonist increases the rate of alveolar fluid clearance in human donor lungs J Appl Physiol 2002; 93:1869

  6. Aerosolized albuterol given via the ventilator circuit reaches therapeutic concentrations (10-6 M) in the distal airspaces Intensive Care Med 2002;28:705

  7. BOLD Study Hypothesis Administration of an inhaled beta-adrenergic agonist (albuterol) will: 1. improve donor oxygenation (primary endpoint) • Improve lung compliance and CXR • improve donor lung utilization rates • Improve pulmonary edema as measured in resected lungs • Improve recipient outcomes

  8. Investigators and Study Personnel Vanderbilt: Lorraine Ware, Minerva Covarrubias, Nancy Wickersham, UCSF: Michael Matthay, Sandy Brady, Jae Woo Lee, Jenny Fang CTDN: Megan Landeck, Eugene Osborne, Ben Chau, Cynthia Ison, the Transplant Coordinators and the APCs

  9. Inclusion and Exclusion Criteria Inclusion Criteria: - Brain death - Consent for research from family - Donor ≥ 14 years of age - Coroner release for lungs to be used for research for Matthay’s lab Exclusion Criteria: - CNP donors (Consent Not Productive) will not be included in final analysis

  10. Study Design • Randomized double blinded design: • Albuterol 5.0 mg aerosolized q4h vs. placebo • Intervention begins immediately when care of donor is assumed by CTDN Enrollment Study Drug Study Drug Study Drug Study Drug Study Drug Study Drug Study Drug Study Drug Study drug q 4h until organ procurement or 72 h Organ Procure- ment 0 1 5 9 13 17 21 25 29 Time (h) Baseline history, chest X-ray, arterial blood gas and blood samples Static lung compliance every 12 hours Repeat chest x-ray, arterial blood gas and blood samples. Recover lungs for laboratory evaluation if not transplanted

  11. Study Update • Enrollment began in late April 2007 • 78 Donors have been enrolled (12 CNP) • No change in overall donor lung utilization rates • Lungs from 33 donors procured for measurement of lung water (Matthay lab)

  12. Adverse Event Monitoring • Heart rate and rhythm monitored after every dose of study drug • Study drug dose reduced (1/2) in two donors due to tachycardia • Study drug stopped in one donor due to tachycardia • No arrhythmias other than sinus tachycardia • No Serious Adverse Events

  13. Looking Ahead • Targeted enrollment: 500 organ donors • Anticipated monthly enrollment ~ 12 donors • Anticipate 36 additional months for full targeted enrollment • DSMB for safety and efficacy at 100 and 300 donors • Study can be stopped early for efficacy

  14. Special Thanks to: • Megan Landeck • The transplant coordinators and APCs • The HLA labs at UCSF, CPMC and Stanford • NIH NHLBI--R01 funding anticipated 01/08

  15. The BOLD StudyBeta-agonists for Oxygenation in Lung Donors

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