POC Strategies to Improve TB Care in Advanced HIV Disease

NCT ID: NCT04122404

Last Updated: 2022-05-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 425 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2022-01-30

Brief 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Intervention

Routine TB diagnostic care (sputum smear microscopy, sputum Xpert MTB/Rif / sputum Xpert MTB/Rif Ultra, sputum culture) + Intervention

Intervention: LF-LAM is made available at the study site for the clinical staff to use; Training of clinical staff in national TB guidelines and LF-LAM use together with staff from the National TB Programme in Ghana

Group Type: OTHER

LF-LAM

Intervention Type: DIAGNOSTIC_TEST

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.

Standard of care

Routine TB diagnostic care (sputum smear microscopy, sputum Xpert MTB/Rif / sputum Xpert MTB/Rif Ultra, sputum culture)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Lateral flow urine lipoarabinomannan assay; Determine TM TB LAM Ag test

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Odense University Hospital

OTHER

Sponsor Role: collaborator

National Tuberculosis Control Programme, Ghana

UNKNOWN

Sponsor Role: collaborator

Odense Patient Data Explorative Network

OTHER

Sponsor Role: collaborator

University of Ghana

OTHER

Sponsor Role: collaborator

Tema General Hospital, Ghana

UNKNOWN

Sponsor Role: collaborator

Lekma Hospital, Ghana

UNKNOWN

Sponsor Role: collaborator

Korle-Bu Teaching Hospital, Ghana

UNKNOWN

Sponsor Role: collaborator

University of Southern Denmark

OTHER

Sponsor Role: lead

Responsible Party

Johanna Maria Åhsberg

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johanna Åhsberg, MD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

Isik Somuncu Johansen, Prof

Role: STUDY_DIRECTOR

Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

Margaret Lartey, Prof

Role: STUDY_CHAIR

School of Medicine and Dentistry, University of Ghana

Stephanie Bjerrum, MD

Role: STUDY_CHAIR

Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

Åse Bengaard Andersen, Prof

Role: STUDY_CHAIR

Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark

Ernest Kenu, MD

Role: STUDY_CHAIR

Dept. of Epidemiology and Disease Control, Univ. of Ghana

Locations

Korle Bu Teaching Hospital

Accra, , Ghana

Tema General Hospital

Tema, , Ghana

Lekma Hospital

Teshie, , Ghana

Countries

Ghana

References

Zifodya JS, Kreniske JS, Schiller I, Kohli M, Dendukuri N, Schumacher SG, Ochodo EA, Haraka F, Zwerling AA, Pai M, Steingart KR, Horne DJ. Xpert Ultra versus Xpert MTB/RIF for pulmonary tuberculosis and rifampicin resistance in adults with presumptive pulmonary tuberculosis. Cochrane Database Syst Rev. 2021 Feb 22;2(2):CD009593. doi: 10.1002/14651858.CD009593.pub5.

Reference Type: DERIVED

PMID: 33616229 (View on PubMed)

Other Identifiers

OP_861

Identifier Type: -

Identifier Source: org_study_id