Extrapulmonary TuberculosisTBPOCNCT04122404
POC Strategies to Improve TB Care in Advanced HIV Disease
A study testing LF-LAM in people with Extrapulmonary Tuberculosis and Tuberculosis, Pulmonary, run by University of Southern Denmark at 3 sites in Ghana.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extrapulmonary Tuberculosis, Tuberculosis, Pulmonary, Human Immunodeficiency Virus (HIV)
- What is being tested?
- LF-LAM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 425 participants
- Where
- 3 sitesGhana
- Study dates
- 14 Oct 2019to 30 Jan 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- Anti-tuberculous treatment including preventive treatment with Isoniazide within the last 60 days
- Earlier participation in the same study
Trial locations and contacts
3 sites in 1 country.
Ghana3 sites
Korle Bu Teaching Hospital
Accra
Tema General Hospital
Tema
Lekma Hospital
Teshie
About this study
Official title: Point-of-care Strategies to Improve Tuberculosis Care Among Severely Immunosuppressed HIV-infected Patients
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.
Read more
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
- Being tested
- LF-LAM
- 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
- Medical subject headings
- Tuberculosis, Extrapulmonary, Tuberculosis, Pulmonary, Acquired Immunodeficiency Syndrome, Tuberculosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LF-LAMDiagnostic test
Also called Lateral flow urine lipoarabinomannan assay, Determine TM TB LAM Ag 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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Other | 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 Receives: Diagnostic Test: LF-LAM |
| Standard of care | No intervention | Routine TB diagnostic care (sputum smear microscopy, sputum Xpert MTB/Rif / sputum Xpert MTB/Rif Ultra, sputum culture) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to TB treatment initiation
Time to TB treatment initiation defined by time from TB diagnosis suspected to start of anti-tuberculous treatment provided.
Measured: 8 weeks follow up
Secondary outcomes (4)
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.
Measured: 8 weeks follow up
TB case detection
Defined as proportion of patients with (i) microbiologically confirmed TB diagnosis and (ii) clinically confirmed TB diagnosis
Measured: 8 weeks follow up
Time to TB diagnosis
Measured: 8 weeks follow up
Time to all-cause mortality.
Mortality rates during follow up. Underpowered
Measured: 8 weeks follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2019
- Study start14 Oct 2019
- Primary completion30 Jan 2022
- Study completion30 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Extrapulmonary TuberculosisStudies of the same condition, open and under way.
- More trials run by University of Southern DenmarkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Sequential
- 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.
- Masking
- None (open label)
- Enrolment
- 425 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern Denmark
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital, National Tuberculosis Control Programme, Ghana, Odense Patient Data Explorative Network, University of Ghana, Tema General Hospital, Ghana, Lekma Hospital, Ghana, Korle-Bu Teaching Hospital, Ghana
- Responsible party
- Principal investigator, Johanna Maria Åhsberg, University of Southern Denmark
- Investigators
- Johanna Åhsberg, MD, Principal investigator, Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern DenmarkIsik Somuncu Johansen, Prof, Study director, Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern DenmarkMargaret Lartey, Prof, Study chair, School of Medicine and Dentistry, University of GhanaStephanie Bjerrum, MD, Study chair, Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern DenmarkÅse Bengaard Andersen, Prof, Study chair, Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern DenmarkErnest Kenu, MD, Study chair, Dept. of Epidemiology and Disease Control, Univ. of Ghana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04122404
- Sponsor's protocol ID
- OP_861
- Acronym
- TBPOC
- Status last verified
- May 2022
- First submitted
- 8 Oct 2019
- Last updated
- 23 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ahsberg J, Puplampu P, Kwashie A, Commey JO, Ganu VJ, Omari MA, Adusi-Poku Y, Andersen AB, Kenu E, Lartey M, Johansen IS, Bjerrum S. Point-of-Care Urine Lipoarabinomannan Testing to Guide Tuberculosis Treatment Among Severely Ill Inpatients With Human Immunodeficiency Virus in Real-World Practice: A Multicenter Stepped Wedge Cluster-Randomized Trial From Ghana. Clin Infect Dis. 2023 Oct 13;77(8):1185-1193. doi: 10.1093/cid/ciad316.
PubMed 37233720Zifodya 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.
PubMed 33616229
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Point-of-care Strategies to Improve Tuberculosis Care Among Severely Immunosuppressed HIV-infected Patients
- ClinicalTrials.gov ID
- NCT04122404
- Acronym / sponsor ID
- TBPOC / OP_861
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 425 participants (actual)
- Lead sponsor
- University of Southern DenmarkUniversity, hospital or other
- Collaborators
- Odense University Hospital, National Tuberculosis Control Programme, Ghana, Odense Patient Data Explorative Network, University of Ghana, Tema General Hospital, Ghana, Lekma Hospital, Ghana, Korle-Bu Teaching Hospital, Ghana
- Study start
- 14 Oct 2019 (actual)
- Primary completion
- 30 Jan 2022 (actual)
- Study completion
- 30 Jan 2022 (actual)
- First posted
- 10 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Intervention | Other | Diagnostic Test: LF-LAMRoutine 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 |
| Standard of care | No intervention | –Routine TB diagnostic care (sputum smear microscopy, sputum Xpert MTB/Rif / sputum Xpert MTB/Rif Ultra, sputum culture) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (2 listed)
- Anti-tuberculous treatment including preventive treatment with Isoniazide within the last 60 days
- Earlier participation in the same study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LF-LAMAlso: Lateral flow urine lipoarabinomannan assay, Determine TM TB LAM Ag testOpen 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. | Diagnostic test | Intervention |
Primary outcome
Time to TB treatment initiation
Time frame: 8 weeks follow up
Time to TB treatment initiation defined by time from TB diagnosis suspected to start of anti-tuberculous treatment provided.
4 secondary outcomes
TB related morbidity
Time frame: 8 weeks follow up
TB case detection
Time frame: 8 weeks follow up
Time to TB diagnosis
Time frame: 8 weeks follow up
Time to all-cause mortality.
Time frame: 8 weeks follow up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2022.
- Derived from this study: PubMed 37233720Ahsberg J, Puplampu P, Kwashie A, Commey JO, Ganu VJ, Omari MA, Adusi-Poku Y, Andersen AB, Kenu E, Lartey M, Johansen IS, Bjerrum S. Point-of-Care Urine Lipoarabinomannan Testing to Guide Tuberculosis Treatment Among Severely Ill Inpatients With Human Immunodeficiency Virus in Real-World Practice: A Multicenter Stepped Wedge Cluster-Randomized Trial From Ghana. Clin Infect Dis. 2023 Oct 13;77(8):1185-1193. doi: 10.1093/cid/ciad316.
- Derived from this study: PubMed 33616229Zifodya 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Johanna Åhsberg, MD principal investigator
Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
Isik Somuncu Johansen, Prof study director
Dept. of Infectious Diseases, Odense University Hosp., Univ. of Southern Denmark
Margaret Lartey, Prof study chair
School of Medicine and Dentistry, University of Ghana
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LF-LAM in people with Extrapulmonary Tuberculosis and Tuberculosis, Pulmonary, run by University of Southern Denmark at 3 sites in Ghana.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Ghana. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to TB treatment initiation (time frame: 8 weeks follow up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04122404, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2022.