Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease

Summary

Sickle cell anemia (SCA) is a life-threatening, monogenic disorder associated with early death when compared to individuals without SCA. Pulmonary complications, namely acute chest syndrome, obstructive lung disease and pulmonary hypertension, are the most common causes of death in patients with SCA. Recent studies suggest that lung specific inflammation is a hallmark of SCA and underlies pulmonary pathology. To date, no therapy has been shown to improve the pulmonary complications of SCA. Macrolides have pleomorphic effects in the lung with improvement in pulmonary function, symptoms and inflammatory markers demonstrated in several inflammatory pulmonary conditions such as cystic fibrosis, asthma, COPD and post-transplant bronchiolitis obliterans. Investigators hypothesize that low dose macrolide therapy is well tolerated and can improve pulmonary function and symptoms in patients with SCA. The objective of this project is to assess the feasibility of macrolides to attenuate or reverse the decrease in %predicted FEV1 in adults with SCA in a single-site, randomized, placebo-controlled feasibility trial.

Timeline

Start

2016-09

Primary completion

2018-10

Completion

2018-10

Publications

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• Background Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.
• Background Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, Nickerson B, Orringer E, McKie V, Bellevue R, Daeschner C, Manci EA. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000 Jun 22;342(25):1855-65. doi: 10.1056/NEJM200006223422502.
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• Background Kassim AA, Payne AB, Rodeghier M, Macklin EA, Strunk RC, DeBaun MR. Low forced expiratory volume is associated with earlier death in sickle cell anemia. Blood. 2015 Sep 24;126(13):1544-50. doi: 10.1182/blood-2015-05-644435. Epub 2015 Aug 10.
• Background Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.
• Background Bakheit AH, Al-Hadiya BM, Abd-Elgalil AA. Azithromycin. Profiles Drug Subst Excip Relat Methodol. 2014;39:1-40. doi: 10.1016/B978-0-12-800173-8.00001-5.

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