Sickle Cell Disease Clinical Trial
Official title:
A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
Verified date | June 2018 |
Source | University of Mississippi Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Acute chest syndrome (ACS), a lung complication in sickle cell disease (SCD), is the second most common cause of hospitalization and leading cause of death in SCD. ACS is associated with airway inflammation, and a major cause is pulmonary infection from atypical organisms. To date, there are no drugs available to reduce inflammation and risk of recurrent ACS. Macrolides are a group of antibiotics that exert immunomodulatory and anti-inflammatory actions both in vitro and in vivo. In addition, macrolides reduce bacterial burden in the airway of atypical organisms, all of which play an important role in the pathophysiology of ACS. Numerous studies have evaluated macrolide prophylaxis in conditions associated with lung inflammation, such as cystic fibrosis, asthma, bronchiectasis etc., and high quality evidence have found macrolides to be beneficial as a disease modifying agent that leads to improvement in airway inflammation, reduced pulmonary exacerbations and improved lung function. The investigators hypothesize that azithromycin prophylaxis is well tolerated and has the potential to reduce inflammation and improve lung outcome in children with SCD with a history of ACS. A prospective, single arm, open label feasibility study of azithromycin prophylaxis will be performed in children with SCD with a history ACS with the specific aim to examine the feasibility, safety and tolerability of azithromycin prophylaxis administration in participants with SCD , and to examine whether azithromycin prophylaxis has the potential to improve lung outcome. In addition, this study will determine whether azithromycin prophylaxis reduces inflammation in participants with SCD with a history of ACS.
Status | Withdrawn |
Enrollment | 0 |
Est. completion date | December 31, 2017 |
Est. primary completion date | December 31, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Years to 16 Years |
Eligibility |
Inclusion Criteria: - Established diagnosis of SCD (Hemoglobin SS, hemoglobin Sß0 thalassemia) - History of acute chest syndrome - the history of acute chest syndrome will be confirmed by a retrospective medical chart review that meets the standard definition as mentioned in the Background section. - Age = 6 years to 16 years old Exclusion Criteria: - Hemoglobin Sß+thalassemia and hemoglobin SC subject will be excluded as this group of patients do not typically have severe SCD that places them at risk of developing recurrent acute chest syndrome - No history of acute chest syndrome - Significant neurologic impairment as judged by health care provider. - Inability to take/swallow a tablet - History of poor adherence to clinic visits. - History of renal or hepatic dysfunction - Chronic red blood cell transfusion - History of allergy to azithromycin or macrolide antibiotic - History of cardiac arrhythmia - History of prolonged QT |
Country | Name | City | State |
---|---|---|---|
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Vanderbilt University | Nashville | Tennessee |
Lead Sponsor | Collaborator |
---|---|
University of Mississippi Medical Center |
United States,
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Castro O, Brambilla DJ, Thorington B, Reindorf CA, Scott RB, Gillette P, Vera JC, Levy PS. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood. 1994 Jul 15;84(2):643-9. — View Citation
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Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-1266. doi: 10.1378/chest.12-0628. — View Citation
Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, Coquillette S, Fieberg AY, Accurso FJ, Campbell PW 3rd; Macrolide Study Group. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003 Oct 1;290(13):1749-56. — View Citation
Vance LD, Rodeghier M, Cohen RT, Rosen CL, Kirkham FJ, Strunk RC, DeBaun MR. Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and asthma cohort. Am J Hematol. 2015 May;90(5):371-5. doi: 10.1002/ajh.23959. Epub 2015 Mar 30. — View Citation
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. Erratum in: N Engl J Med 2000 Sep 14;343(11):824. — View Citation
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Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 48 weeks | ||
Secondary | Percent adherence with azithromycin prophylaxis | 48 weeks | ||
Secondary | Number of participants with improved forced vital capacity (cm3) | 48 weeks | ||
Secondary | Number of participants with improved forced expiratory volume 1 (cm3/sec) | 48 weeks |
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