A Pragmatic Randomised Study to Optimise Screening, Prevention and Care for Tuberculosis in Malawi

Summary

A pragmatic open, three-arm individually-randomised controlled trial and economic evaluation will be conducted in one primary health care centre in Blantyre, Malawi, where HIV and TB are major contributors to early mortality.

Participants will be adults with symptoms of tuberculosis (cough of any duration) attending the primary clinic with an acute care episode. We will exclude adults who have taken treatment for TB within the previous 6-months, who are taking isoniazid preventive therapy, who are not resident of Blantyre, or who plan to move out of Blantyre in the following 6-months.

Participants will be randomly allocated into one of three groups:

Group 1: Standard of care: Participants will be seen by facility health workers and receive clinician-directed screening for HIV and TB according to Malawi national guidelines.

Group 2: Optimised HIV testing and treatment linkage: Participants will be offered testing for HIV using rapid oral fluid kits by research assistants. Those with confirmed HIV infection will be linked to the HIV care clinic where facility healthworkers will screen for TB using standard sputum-based diagnostics.

Group 3: Optimised TB diagnosis, HIV screening and treatment linkage: Participants will receive a high-throughput and high-sensitivity TB screening intervention, in addition to the HIV testing intervention. This will comprise of an initial digital chest x-ray classified by the CAD4TB image-recognition software as either "high probability of TB", or "low probability of TB". Participants whose x-rays are suggestive of TB will receive confirmatory sputum testing with Xpert MTB/Rif Ultra cartridges, whilst participants whose x-rays have a low probability of TB will be referred to facility healthworkers for routine care.

All participants will be seen at the health facility at day 56, where they will be tested for HIV (if not on ART) and screened for TB.

The Primary Trial Outcome will compare between groups the time to tuberculosis treatment initiation by day 56. The trial is sufficiently powered to permit 3 pairwise comparisons between groups (i.e. Group 1 vs. 2; Group 2 vs. 3; and Group 1 vs. 3).

This three-arm pragmatic trial design allows us to efficiently answer two separate, important public health questions: firstly, by comparing Group 2 to Group 1, we should be able to determine whether HIV care should be prioritised for adults with TB symptoms. Additionally, by comparing Group 3 to Group 2, we will provide strong evidence for the effectiveness of an optimised and integrated HIV and TB diagnostic and treatment linkage approach.

Conditions

• Tuberculosis
• Hiv
• Tuberculosis, Pulmonary

Interventions

OTHER

Optimised HIV screening and linkage to care

As described in group descriptions

OTHER

Optimised tuberculosis screening and linkage to care

As described in group descriptions

Sponsors & Collaborators

• Malawi-Liverpool-Wellcome Trust Clinical Research Programme

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  collaborator OTHER

• University of Liverpool

  collaborator OTHER

• McGill University

  collaborator OTHER

• Kamuzu University of Health Sciences

  collaborator OTHER

• Liverpool School of Tropical Medicine

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-11-15

Primary Completion

2019-12-31

Completion

2020-06-30

Countries

• Malawi

Study Locations