Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results.
BACKGROUND
Biologic lung volume reduction (BioLVR) is a new endobronchial treatment for advanced emphysema that reduces lung volume through tissue remodeling.


OBJECTIVE
Assess the safety and therapeutic dose of BioLVR hydrogel in upper lobe predominant emphysema.


METHODS
Open-labeled, multicenter phase 2 dose-ranging studies were performed with BioLVR hydrogel administered to eight subsegmental sites (four in each upper lobe) involving: (1) low-dose treatment (n = 28) with 10 ml per site (LD); and (2) high-dose treatment (n = 22) with 20 ml per site (HD). Safety was assessed by the incidence of serious medical complications. Efficacy was assessed by change from baseline in pulmonary function tests, dyspnea score, 6-minute walk distance, and health-related quality of life.


RESULTS
After treatment there were no deaths and four serious treatment-related complications. A reduction in residual volume to TLC ratio at 12 weeks (primary efficacy outcome) was achieved with both LD (-6.4 +/- 9.3%; P = 0.002) and HD (-5.5 +/- 9.4%; P = 0.028) treatments. Improvements in pulmonary function in HD (6 mo: DeltaFEV(1) = +15.6%; P = 0.002; DeltaFVC = +9.1%; P = 0.034) were greater than in LD patients (6 mo: DeltaFEV(1) = +6.7%; P = 0.021; DeltaFVC = +5.1%; P = 0.139). LD- and HD-treated groups both demonstrated improved symptom scores and health-related quality of life.


CONCLUSIONS
BioLVR improves physiology and functional outcomes up to 6 months with an acceptable safety profile in upper lobe predominant emphysema. Overall improvement was greater and responses more durable with 20 ml per site than 10 ml per site dosing. Clinical trial registered with www.clinicaltrials.gov (NCT 00435253 and NCT 00515164).
Criner
Gerard J
GJ
Temple Lung Center, Temple University School of Medicine, 745 Parkinson Pavilion, 3401 North Broad Street, Philadelphia, PA 19140. crinerg@tuhs.temple.edu
Pinto-Plata
Victor
V
Strange
Charlie
C
Dransfield
Mark
M
Gotfried
Mark
M
Leeds
William
W
McLennan
Geoffrey
G
Refaely
Yael
Y
Tewari
Sanjiv
S
Krasna
Mark
M
Celli
Bartolome
B
D000368:Aged; D001999:Bronchoscopy; D004417:Dyspnea / Q000628:therapy; D005221:Fatigue / Q000209:etiology; D005260:Female; D005334:Fever / Q000209:etiology; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage* / Q000009:adverse effects; D007964:Leukocytosis / Q000209:etiology; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000628:therapy; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging / Q000628:therapy*; D011788:Quality of Life; D011859:Radiography; D012129:Respiratory Function Tests
C540466:BioLVR hydrogel; D020100:Hydrogels