POC Strategies to Improve TB Care in Advanced HIV Disease

Summary

Tuberculosis (TB) remains the major cause of morbidity and mortality among patients with HIV. Sub-optimal diagnostics contributes towards poor patient outcome and there is an urgent need to identify non-sputum-based point-of-care diagnostic tests. The urine based lateral flow lipoarabinomannan TB diagnostic test (LF-LAM) is a simple, inexpensive point-of-care test. In 2015, the World Health Organization endorsed LF-LAM for conditional use among patients with advanced HIV, but uptake of the test in clinical practices has been poor.

The investigators aim to identify point-of-care (POC) strategies that can improve TB case detection and clinical outcomes among patients with advanced HIV. The project includes a main study and two sub-studies.

The main study is a multicenter stepped wedge cluster-randomized controlled trial of LF-LAM implementation among patients with advanced HIV with 8-weeks follow-up. LF-LAM will be added to standard care and implemented stepwise at three hospitals in Ghana. Education in national TB treatment guidelines in collaboration with the Tuberculosis Control programme in Ghana, and Clinical audit of clinical staff with feedback, will be used to assess and strengthen LF-LAM implementation. The primary outcome time to TB treatment, for which a sample size of 690 participants will provide \>90% power to detect a minimum of 7 days reduction. Secondary outcomes are: TB related morbidity, TB case detection, time to TB diagnosis and overall early mortality at 8 weeks. The HIV-associated TB epidemiology including genotypic analyses of M. tuberculosis isolates obtained through the main study will be described. In sub study A, focused ultrasound of lungs, heart and abdomen will be performed in a sub cohort of 100 participants. In sub study B, the investigators will establish a biobank and data warehouse for storage of blood, urine and sputum samples collected from participants that enter the study at Korle-Bu Teaching hospital.

It is expected that LF-LAM will lead to earlier diagnosis and treatment of TB. Findings may further guide scaling-up of LF-LAM. The HIV-associated epidemic including genotypic properties and resistance properties which is important for improved management will be detailed. The investigators further expect to evaluate the potential of bedside ultrasound as a clinical tool in management of HIV/TB co-infected patients. The unique Ghanaian HIV-cohort and biobank may facilitate rapid evaluation of future prognostic biomarkers and new point-of-care TB diagnostic tests.

Conditions

• Extrapulmonary Tuberculosis
• Tuberculosis, Pulmonary
• Human Immunodeficiency Virus (HIV)
• Acquired Immunodeficiency Syndrome

Interventions

DIAGNOSTIC_TEST

LF-LAM

Open label multi-center stepped wedge cluster-randomized controlled trial with implementation of LF-LAM. All clusters (i.e. HIV/ART clinic attached wards) start with standard of care and are then randomized to switch to the intervention phase at predefined time points.

Sponsors & Collaborators

• Odense University Hospital

  collaborator OTHER

• National Tuberculosis Control Programme, Ghana

  collaborator UNKNOWN

• Odense Patient Data Explorative Network

  collaborator OTHER

• University of Ghana

  collaborator OTHER

• Tema General Hospital, Ghana

  collaborator UNKNOWN

• Lekma Hospital, Ghana

  collaborator UNKNOWN

• Korle-Bu Teaching Hospital, Ghana

  collaborator UNKNOWN

• University of Southern Denmark

  lead OTHER

Principal Investigators

• Johanna Åhsberg, MD · Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

• Isik Somuncu Johansen, Prof · Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

• Margaret Lartey, Prof · School of Medicine and Dentistry, University of Ghana

• Stephanie Bjerrum, MD · Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

• Åse Bengaard Andersen, Prof · Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

• Ernest Kenu, MD · Dept. of Epidemiology and Disease Control, Univ. of Ghana

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-14

Primary Completion

2022-01-30

Completion

2022-01-30

Countries

• Ghana

Study Locations