A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease

• Status: Withdrawn
• Trial end date: 2017-12-31
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Mississippi Medical Center
• Treatments: Azithromycin

Criteria

Inclusion Criteria:

• Established diagnosis of SCD (Hemoglobin SS, hemoglobin Sβ0 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 Sβ+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