POC Strategies to Improve TB Care in Advanced HIV Disease

Acquired Immunodeficiency Syndrome Clinical Trial

— TBPOC  

Official title:

Point-of-care Strategies to Improve Tuberculosis Care Among Severely Immunosuppressed HIV-infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04122404
• Other study ID #: OP_861
• Status: Completed
• Phase: N/A
• Start date: October 14, 2019
• Est. completion date: January 30, 2022

Study information

• Verified date: May 2022
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 425
• Est. completion date: January 30, 2022
• Est. primary completion date: January 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-positive

• 18 years and above

• Able to give informed consent

• Admitted at the wards attached to the research site ART/HIV-clinic

• Eligible for LF-LAM testing (defined by WHO in the LF-LAM policy update 2019):

CD4-cell-count =200 cells/µL (the last measured CD4-cell-count); or a WHO clinical stage 3 or 4 event at presentation for care; or seriously ill defined by WHO (respiratory rate > 30/min, temperature > 39°C, heart rate > 120/min or unable to walk unaided); or a positive WHO TB symptom screening including one of the following symptoms: current cough, fever, weight loss, or night sweats

Exclusion Criteria:

• Anti-tuberculous treatment including preventive treatment with Isoniazide within the last 60 days

• Earlier participation in the same study

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Extrapulmonary Tuberculosis
• HIV Infections
• Human Immunodeficiency Virus (HIV)
• Immunologic Deficiency Syndromes
• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

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.

Locations

Country	Name	City	State
Ghana	Korle Bu Teaching Hospital	Accra
Ghana	Tema General Hospital	Tema
Ghana	Lekma Hospital	Teshie

Sponsors (8)

Lead Sponsor	Collaborator
University of Southern Denmark	Korle-Bu Teaching Hospital, Ghana, Lekma Hospital, Ghana, National Tuberculosis Control Programme, Ghana, Odense Patient Data Explorative Network, Odense University Hospital, Tema General Hospital, Ghana, University of Ghana

Country where clinical trial is conducted

Ghana, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to TB treatment initiation	Time to TB treatment initiation defined by time from TB diagnosis suspected to start of anti-tuberculous treatment provided.	8 weeks follow up
Secondary	TB related morbidity	The difference in the proportion of TB patients with reduced TB morbidity score at 8 weeks follow up using "The Bandim tuberculosis score" with grading 0-13, where a reduction in the score may be used as a measurement of clinical improvement.	8 weeks follow up
Secondary	TB case detection	Defined as proportion of patients with (i) microbiologically confirmed TB diagnosis and (ii) clinically confirmed TB diagnosis	8 weeks follow up
Secondary	Time to TB diagnosis		8 weeks follow up
Secondary	Time to all-cause mortality.	Mortality rates during follow up. Underpowered	8 weeks follow up