A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
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|ClinicalTrials.gov Identifier: NCT02630394|
Recruitment Status : Withdrawn (Principal Investigator has moved to another institution)
First Posted : December 15, 2015
Last Update Posted : June 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell Disease Acute Chest Syndrome||Drug: Azithromycin||Phase 1|
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 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 following specific aims:
Specific Aim 1: Examine the feasibility, safety and tolerability of azithromycin prophylaxis administration in children with SCD. A cohort of 15 participants with sickle cell disease 6 to 16 years old will be placed on azithromycin prophylaxis, and followed closely to evaluate medication adherence and for any adverse effects from taking the medication.
Specific Aim 2: Examine whether azithromycin prophylaxis has the potential to improve lung outcome in participants with SCD with a history of ACS. In the same cohort of 15 patients, baseline pulmonary function testing will be performed evaluating Forced expiratory volume 1 sec (FEV1) and Forced vital capacity (FVC) measurements prior to starting azithromycin prophylaxis, and then again at study end period after 1 year to evaluate for any change.
Specific Aim 3: Determine whether azithromycin prophylaxis reduces inflammation in participants with SCD with a history of ACS. In the same cohort of 15 participants, baseline markers of inflammation will be performed, specifically C-reactive protein (CRP), Tumor necrosis factor Alpha (TNF-α), interleukin IL-1, IL-1β, IL-4, IL-6, and IL-8, and then repeated at specific time intervals of 16 weeks, 32 weeks and 48 weeks (study end).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease|
|Study Start Date :||September 2015|
|Estimated Primary Completion Date :||December 31, 2017|
|Actual Study Completion Date :||December 31, 2017|
Experimental: Azithromycin prophylaxis
Azithromycin will be supplied as a 250-mg tablet. Participants weighing less than 40 mg will be instructed to take 1 tablet 3 days a week (Monday, Wednesday, and Friday), and participants who weigh more than 40 kg will be instructed to take 2 tablets on the same 3 days per week.
Other Name: Zithromax
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 48 weeks ]
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02630394
|United States, Mississippi|
|University of Mississippi Medical Center|
|Jackson, Mississippi, United States, 39216|
|United States, Tennessee|
|Nashville, Tennessee, United States|