Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children
Condition: Chronic Lung Disease; HIV Infection
MeSH terms: Lung Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      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:

        1. 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.

        2. Secondary objectives:

             1. To investigate the intervention effect on mortality, exacerbations of lung disease,
                quality of life, morbidity.

             2. 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.
    

Detailed description: 
      Clinical Phase: III

      Trial Design: Multi-site, individually randomised, double-blinded, placebo-controlled trial
      of weekly azithromycin for 12 months

      Trial Participants: Children aged 6-16 years living with HIV and with diagnosis of chronic
      lung disease. Another 200 children living with HIV but with no chronic lung disease in a
      comparison arm.

      Planned Sample Size: 400 cases and 100 in the comparison arm

      Treatment duration: 12 months

      Follow up duration: 18 months

      Planned Trial Period: June 2016-September 2019

      Objectives:

        -  Primary trial outcome: 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.

        -  Secondary trial outcomes:

      .To investigate the intervention effect on mortality,exacerbations of lung disease, quality
      of life and morbidity..

      .To investigate adverse events related to azithromycin treatment. .-Laboratory sub-studies
      .To determine the effect of azithromycin therapy on antimicrobial resistance in bacteria
      colonizing the respiratory tract.

      .To investigate the diversity and composition of the respiratory microbiome in HIV-infected
      children with CLD.

      .To investigate the diversity and composition of the gut microbiome in HIV-infected children
      with CLD.

      .To investigate the effect of azithromycin on biomarkers of systemic inflammation in
      HIV-infected children with CLD.

      .-Cardiac sub-study: .Describe the cardiac symptoms and echocardiograph findings of
      HIV-infected children with chronic lung disease.

      .To investigate whether adjuvant treatment with azithromycin results in improvement in
      right-sided cardiac function and/or pulmonary hypertension in HIV-infected children with
      chronic lung disease.

      Investigational Medicinal Product(s): Azithromycin and placebo.

      Formulation:Tablets 250 mg

      Dose: According to weight bands (30 mg/kg/week):

        -  10-20 kg: 250 mg

        -  20-29 kg: 500 mg

        -  30-39 kg: 750 mg

        -  40-49 kg: 1250 mg

      Route of Administration:Oral
    

Intervention name(s): Azithromycin; Placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Azithromycin
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment