Clinical trial NCT04122404: POC Strategies to Improve TB Care in Advanced HIV Disease
Official title: Point-of-care Strategies to Improve Tuberculosis Care Among Severely Immunosuppressed HIV-infected Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Extrapulmonary Tuberculosis
Tuberculosis, Pulmonary
Human Immunodeficiency Virus (HIV)
Acquired Immunodeficiency Syndrome
Keywords: Point-of-care systems
Tuberculosis/Diagnosis
Biomarkers/Urin
Lipopolysaccharides/urine
Audit intervention
Diagnostic tests/Routine
Ultrasound
Bedside
Biobank
Stepped wedge cluster randomised trial
Multicenter study
Audit and feedback
Ghana
Adult
Hospitalization
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
Collaborators: name: Odense University Hospital
name: National Tuberculosis Control Programme, Ghana
name: Odense Patient Data Explorative Network
name: University of Ghana
name: Tema General Hospital, Ghana
name: Lekma Hospital, Ghana
name: Korle-Bu Teaching Hospital, Ghana
First posted: 2019-10-10
Enrollment: 425
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Open label multi-center stepped wedge cluster-randomized controlled implementation trial of the use of urine-based LF-LAM in addition to routine sputum-based TB diagnostic tests to guide initiation of TB treatment among adult hospitalized patients with advanced HIV. The design offers a randomised method of evaluation of the intervention at cluster level. Applying the stepped wedge design ensures that all participating HIV/ART clinic attached wards will have received the intervention at the end of the study period, and provides the basis for the LF-LAM test to become an integrated part of TB health care services also after the project finishes. Clinic staff will be trained on how to use and interpret the LF-LAM test and in TB diagnostic guidelines as outlined by WHO. An Audit and feedback study will identify leaky steps in the TB diagnostic pathway and further strengthen the implementation and possible impact of the LF-LAM test.
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: Time to TB treatment initiation
timeFrame: 8 weeks follow up
Secondary outcomes:
measure: TB related morbidity
timeFrame: 8 weeks follow up
measure: TB case detection
timeFrame: 8 weeks follow up
measure: Time to TB diagnosis
timeFrame: 8 weeks follow up
measure: Time to all-cause mortality.
timeFrame: 8 weeks follow up
Other outcomes:
Locations:
city: Accra
country: Ghana
facility: Korle Bu Teaching Hospital
city: Tema
country: Ghana
facility: Tema General Hospital
city: Teshie
country: Ghana
facility: Lekma Hospital
Study officials:
affiliation: Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
name: Johanna Åhsberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
name: Isik Somuncu Johansen, Prof
role: STUDY_DIRECTOR
affiliation: School of Medicine and Dentistry, University of Ghana
name: Margaret Lartey, Prof
role: STUDY_CHAIR
affiliation: Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
name: Stephanie Bjerrum, MD
role: STUDY_CHAIR
affiliation: Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
name: Åse Bengaard Andersen, Prof
role: STUDY_CHAIR
affiliation: Dept. of Epidemiology and Disease Control, Univ. of Ghana
name: Ernest Kenu, MD
role: STUDY_CHAIR
References:
citation: 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.