Clinical Trial: A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
Brief 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.
Detailed Summary:
Specific Aims:
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. Recurrent ACS has been associated with poor lung function outcome that is comparable to cystic fibrosis. 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. Thus newer therapies are urgently needed to address this important issue associated with increased morbidity from debilitating chronic lung disease and mortality in SCD. Macrolides are a group of antibiotics that exert immunomodulatory and anti-inflammatory actions both in vitro and in vivo. It has been shown to inhibit neutrophil activation and mobilization, modulate oxidant production by neutrophils and of proinflammatory cytokine synthesis and release by leukocytes, reduce systemic markers of inflammation, inhibit intercellular adhesion molecules on epithelial cell surfaces, and block the activation of certain nuclear transcription factors. In addition, macrolides reduce bacterial burden in the airway of atypical organisms, all of which play an important role in the pathophysiology of ACS. Indeed, 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. However, azithromycin has never been studied before in SCD. 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 AC
Sponsor: University of Mississippi Medical Center
Current Primary Outcome: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 48 weeks ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Percent adherence with azithromycin prophylaxis [ Time Frame: 48 weeks ]
- Number of participants with improved forced vital capacity (cm3) [ Time Frame: 48 weeks ]
- Number of participants with improved forced expiratory volume 1 (cm3/sec) [ Time Frame: 48 weeks ]
Original Secondary Outcome: Same as current
Information By: University of Mississippi Medical Center
Dates:
Date Received: November 26, 2015
Date Started: September 2015
Date Completion:
Last Updated: December 11, 2015
Last Verified: December 2015
