Bronchopulmonary Function in Response to Azithromycin Treatment for Chronic Lung Disease in HIV-infected Children

• Status: Completed
• Trial end date: 2019-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: Biomedical Research and Training Institute Zimbabwe; Biomedical Research and Training Institute, Zimbabwe; Malawi-Liverpool-Wellcome Trust Clinical Research Programme; University of Cape Town; University of Oxford; University of Tromso
• Treatments: Azithromycin

Criteria

Inclusion Criteria:

1. Diagnosis of chronic lung disease (defined as FEV1 and/or FVC <80% predicted)

2. Age 6-19 years

3. Perinatally-acquired HIV infection the most likely source of transmission

4. On first or second-line ART for at least one year

5. HIV-1 viral load undetectable (as defined by each trial site)

6. A firm home address accessible for visiting and intending to remain there for 24 months

7. Willing to agree to participate in the study and to give samples of blood and sputum

8. HIV status disclosed to child for those aged older than 12 years

Exclusion Criteria:

1. Any condition (except HIV) that may prove fatal during the study period (e.g. malignancy, end-stage HIV disease or other conditions deemed likely fatal by the trial physician)

2. Diagnosis of active pulmonary TB

3. Infection with non-tuberculous mycobacteria (NTM)

4. Pregnant or breast-feeding

5. Condition likely to lead to lack of understanding of study procedures or to uncooperative behaviour e.g. neurocognitive disease, developmental delay or psychiatric illness

6. History of prolonged QTc syndrome or current or planned therapy with drugs likely to cause cardiac dysrhythmias

7. Abnormal ECG findings

8. Acute respiratory tract infection during enrolment (patients will be eligible once their acute infection is treated)

9. Creatinine clearance of <30mls/minute

10. ALT more than 2 times the upper limit of normal

11. No defined guardian/stable caregiver

12. No consent/assent from guardian/child