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

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.

Conditions

• Chronic Lung Disease
• HIV Infection

Interventions

DRUG

Azithromycin

DRUG

Placebo

Sponsors & Collaborators

• Biomedical Research and Training Institute, Zimbabwe

  collaborator OTHER

• Malawi-Liverpool-Wellcome Trust Clinical Research Programme

  collaborator OTHER

• University of Tromso

  collaborator OTHER

• University of Cape Town

  collaborator OTHER

• University of Oxford

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  lead OTHER

Principal Investigators

• Rashida Ferrand · London School of Hygiene and Tropical Medicine

• Jon O Odland · University of Tromso

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

SINGLE_GROUP

Eligibility

Min Age

6 Years

Max Age

19 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-06-30

Primary Completion

2018-09-30

Completion

2019-08-31

Countries

• Malawi
• Zimbabwe

Study Locations