Ignite Creation Date:
2024-05-06 @ 7:56 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02630394
Status:
WITHDRAWN
Last Update Posted:
2018-06-21
First Post:
2015-11-26
Brief Title:
A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
Sponsor:
University of Mississippi Medical Center
Organization:
University of Mississippi Medical Center
Study Overview
Official Title:
A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
Status:
WITHDRAWN
Status Verified Date:
2018-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Principal Investigator has moved to another institution
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
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 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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None