The BOLD Study B eta-agonists for O xygenation in L ung D onors
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Transcript of The BOLD Study B eta-agonists for O xygenation in L ung D onors
The BOLD Study
Beta-agonists for Oxygenation in Lung Donors
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
The majority of organ donors have some degree of pulmonary edema
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Percent of Patients
Degree of Pulmonary Edema
None (< 4.2)Mild (4.2-5.0)Moderate/severe (>5.0)
Mean Wet to Dry Ratio 4.4 ± 0.6 in 29 organ donors whose lungs were rejected for transplantation
Lancet 2002; 360: 619-20
Alveolar fluid clearance is intact in the majority of lungs rejected for transplantation
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Alveolar Fluid Clearance
Impaired < 3%/hIntact ≥ 3%/h
Mean Alveolar Fluid Clearance 4.7 ± 2.4 %/h
Lancet 2002; 360: 619-20
A beta-adrenergic agonist increases the rate of alveolar fluid clearance in human donor lungs
J Appl Physiol 2002; 93:1869
Aerosolized albuterol given via the ventilator circuit reaches therapeutic concentrations (10-6 M) in the distal airspaces
Intensive Care Med 2002;28:705
BOLD Study Hypothesis
Administration of an inhaled beta-adrenergic agonist (albuterol) will:
1. improve donor oxygenation (primary endpoint)
2. Improve lung compliance and CXR3. improve donor lung utilization rates4. Improve pulmonary edema as measured
in resected lungs5. Improve recipient outcomes
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
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
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
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Baseline history, chest X-ray, arterial blood gas and blood samples
Static lung compliance every 12 hours
Study drug q 4h until organ procurement or 72 h
Repeat chest x-ray, arterial blood gas and blood samples. Recover lungs for laboratory evaluation if not transplanted
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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)
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
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
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
The BOLD Study
Beta-agonists for Oxygenation in Lung Donors