Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children (BREATHE)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02426112|
Recruitment Status : Recruiting
First Posted : April 24, 2015
Last Update Posted : August 24, 2017
Chronic pulmonary disease (CLD) is the most common manifestation of HIV/AIDS among children, accounting for more than 50% of HIV-associated mortality. Recently, a novel form of CLD, affecting more than 30% of African HIV-infected older children was described by Ferrand et al in Zimbabwe, high-resolution CT scanning findings showed predominantly small airways disease consistent with constrictive obliterative bronchiolitis (OB). . Azithromycin has anti-inflammatory activity and treatment of CLD with this agent may lead to suppression of generalized immune activation.
This specific aims of this project are to:
- Primary objective: To investigate whether adjuvant treatment with azithromycin results in improvement in lung function in HIV-infected children with chronic lung disease, who are stable on antiretroviral therapy.
- To investigate the intervention effect on mortality, exacerbations of lung disease, quality of life, morbidity.
- To investigate adverse events related to azithromycin treatment
In total, 400 children aged 6-16 years, living with HIV and diagnosed with CLD will be enrolled at Harare Children´s Hospital in Harare (Zimbabwe) and Queen Elizabeth Central Hospital in Blantyre (Malawi). These will receive weekly treatment with azithromycin or placebo during 12 months. Another 100 children (50 per site) living with HIV but with no CLD will be enrolled as a comparison group for laboratory sub-studies.
Lung function will be assess using spirometry and the Forced expiratory volume in the first minute (FEV1) will be the primary outcome. The mean change in FEV1 z-score levels will be compared between trial arms after 12 months of initiation of azithromycin treatment.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Lung Disease HIV Infection||Drug: Azithromycin Drug: Placebo||Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||400 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children|
|Study Start Date :||June 2016|
|Estimated Primary Completion Date :||October 2018|
|Estimated Study Completion Date :||October 2019|
Active Comparator: Azithomycin
Azithromycin tablets 250 mg, 30mg/kg/week by mouth, once a week for 12 months.
Placebo Comparator: Placebo
Placebo tablets 250 mg, 30 mg/kg/week by mouth, once a week for 12 months.
- Forced Expiratory Volume in one second z score (FEV1) [ Time Frame: 12 months ]Change in FEV1after 12 months of initiation of therapy with azithromycin
- Forced Expiratory Volume in one second z score (FEV1) [ Time Frame: 24 months ]Mean change in FEV1 24 months after treatment initiation with azithromycin
- Time to death [ Time Frame: 12 months ]Time to death 12 months after treatment initiation with azithromycin
- Time to first acute exacerbation [ Time Frame: 12 months ]
- Number of hospitalizations [ Time Frame: 12 and 24 months ]
- Number of exacerbations [ Time Frame: 12 and 24 months ]
- Quality of life scores [ Time Frame: 12 and 24 months ]
- Mean change in weight-for-age z-score [ Time Frame: 12 and 24 months ]
- Number of mild, moderate and severe adverse events [ Time Frame: 12 months ]
- Number of Malaria episodes (Malawi only) [ Time Frame: 12 months ]
- Number of blood stream infections due to Salmonella typhi and non-typhi [ Time Frame: 12 months ]
- Number of gastroenteritis episodes [ Time Frame: 12 months ]
- Macrolide resistance [ Time Frame: 12 months ]Prevalence of colonization with macrolide (and multidrug-resistant) Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae in the two trial arms at 12 months of initiation of treatment with azithromycin
- Lung microbiome [ Time Frame: baseline, 12 and 14 months ]Composition and diversity of the respiratory bacterial microbiome (determined by culture of clinically relevant organisms and sequencing of 16s rRNA gene amplicons)
- Gut microbiome [ Time Frame: baseline, 12 and 24 months ]Composition and diversity of the gut bacterial microbiome (determined by culture of clinically relevant organisms and sequencing of 16s rRNA gene amplicons
- Inflammation biomarkers [ Time Frame: baseline, 12 and 24 months ]Association between inflammation biomarker levels and FEV1
- Cardiac dysfunction [ Time Frame: Baseline ]prevalence of right sided cardiac dilatation and dysfunction
- Cardiac dysfunction after treatment [ Time Frame: 12 and 24 months ]Prevalence of right sided cardiac dilatation and dysfunction at 12 and 24 months of initiation of azithromycin therapy by intervention arm
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02426112
|Contact: Carmen Gonzalez||+265991416730||Carmen.Gonzalez@lstmed.ac.uk|
|Malawi-Liverpool-Wellcome Trust Clinical Research Programme||Recruiting|
|Blantyre, Malawi, 30096|
|Contact: Carmen Gonzalez +265991416730 Carmen.Gonzalez@lstmed.ac.uk|
|Principal Investigator: Carmen Gonzalez|
|Biomedical Research and Training Institute||Recruiting|
|Contact: Rashida Ferrand +263 (4) 333091 email@example.com|
|Contact: Ethel Dauya +263 7744 52172 firstname.lastname@example.org|
|Principal Investigator: Rashida Ferrand|
|Principal Investigator:||Rashida Ferrand||London School of Hygiene and Tropical Medicine|
|Principal Investigator:||Jon O Odland||University of Tromso|