期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 183, 期 4, 页码 531-538出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201003-0422OC
关键词
bronchiolitis obliterans; antiviral therapy; viral pneumonia
资金
- Alnylam Pharmaceuticals, Inc., Cambridge, MA
- Cubist Pharmaceuticals, Inc., Lexington, MA
- AstraZeneca
- Novartis
- Retroscreen
- Tibotec
- Arrow Pharmaceuticals
- Micro Dose Therapeutx
- Roche Pharmaceuticals
- Gilead Sciences
- Alnylam Pharmaceuticals
- ADMA Pharmaceuticals
- NIH
- Alnylam
- Actelion
- Gilead
- Boehringer Ingelheim
- Pfizer
- Roche
- Wyeth
- Astellas
- Alnylam Pharmaceuticals, Inc.
- CSL Behring
- APT Pharmaceuticals
Rationale: Lower respiratory tract infections due to respiratory syncytial virus (RSV) are associated with development of bronchiolitis obliterans syndrome in lung transplant (LTX) recipients. ALN-RSV01 is a small interfering RNA targeting RSV replication. Objectives: To determine the safety and explore the efficacy of ALN-RSV01 in RSV infection. Methods: We performed a randomized, double-blind, placebo-controlled trial in LTX recipients with RSV respiratory tract infection. Patients were permitted to receive standard of care for RSV. Aerosolized ALN-RSV01 (0.6 mg/kg) or placebo was administered daily for 3 days. Viral load was determined by quantitative reverse transcriptase polymerase chain reaction on serial nasal swabs. Patients completed symptom score cards twice daily. Lung function, including the incidence of new-onset or progressive bronchiolitis obliterans syndrome, was recorded at Day 90. Measurements and Main Results: We enrolled 24 patients (ALN-RSV01, n = 16; placebo, n = 8); randomization was stratified by ribavirin use. ALN-RSV01 was well tolerated, with no drug-related serious adverse events or post-inhalation perturbations in lung function. Interpretation of viral measures was confounded by baseline differences between the two groups in viral load and time from symptom onset to first dose. Mean daily symptom scores were lower in subjects receiving ALN-RSV01, and the mean cumulative daily total symptom score was significantly lower with ALN-RSV01 (114.7 +/- 63.13 vs. 189.3 +/- 99.59, P = 0.035). At Day 90, incidence of new or progressive bronchiolitis obliterans syndrome was significantly reduced in ALN-RSV01 recipients compared with placebo (6.3% vs. 50%, P = 0.027). Conclusions: ALN-RSV01 was safe and may have beneficial effects on long-term allograft function in LTX patients infected with RSV. Clinical trial registered with www.clinicaltrials.gov (NCT 00658086).
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据