A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV

NCT ID: NCT04043390

Last Updated: 2021-08-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-21

Study Completion Date

2020-12-31

Brief Summary

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TB is a major public health problem and the second most common cause of adult death due to infection in many low-income countries. Despite major efforts to de-centralise services, accessibility to diagnosis is still limited, with one third of the 9 million cases occurring each year being missed by national control programmes.

New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are intended for screening purposes, as an initial step to identify individuals who may have TB and should undergo further tests for confirmation. These tests may have high sensitivity, but also give false-positive results (low specificity). Other tests aim to be the confirmatory tests for TB (high specificity), but these tests are often more expensive and complex and are only available in hospital laboratories. As these tests have different purposes, it is likely they would work better in combination in a step fashion to optimise their impact and to develop an efficient diagnostic process. Furthermore, as none of the tests is versatile enough to be used in all settings, test combinations will need to consider the health system context in which they would be used. Our aim is to develop and evaluate rapid and accurate diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the same day of the initial consultation in Africa.

The objectives are to

1. Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care;
2. Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB, allowing patients to reach clinical management decisions within a single clinic visit;
3. Determine the impact of using novel point-of-care diagnostic combinations on the proportion of patients correctly initiating TB treatment within 24-48 hours of first attendance; their potential cost effectiveness

The investigators conducted studies in 2016-2018 to accomplish the first two objectives and have identified diagnostic tests that are suitable for low and middle income countries.

This document therefore refers to objective 3, which aims to

1. Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
2. Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and
3. Assess the cost of the two diagnostic schemes compared to Xpert.

Detailed Description

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The study will enrol patients in TB clinics based in 4 selected district hospitals (two in Nigeria and two in Ethiopia) and samples will be processed in a single reference laboratory. This diagnostic evaluation trial will comprise two experimental diagnostic schemes which will be compared against the standard of care:

* One experimental arm (scheme 1) will screen all patients for HIV using two rapid tests routinely used by the clinics and a rapid CRP. Selected patients will be further tested using ULTRA. Individuals with HIV will undergo an HIV VL using Xpert.
* A second experimental arm (scheme 2): will screen individuals for HIV and CRP (as in scheme 1) and selected patients will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and Truenat RIF.
* In addition, all patients will be tested using the standard of care consistent of confirmatory HIV and CRP tests, Xpert MTB/RIF and culture.

* Randomisation All patients will be randomised at a ratio of 1:1 into schemes 1 and 2. Random numbers will be generated in LSTM by a statistician independent to the study. The scheme allocations will be included in study envelopes assigned to individual study numbers. Equal number of participants will be included in Nigeria and Ethiopia.
* Proposed methods for protecting against source bias

As this is an open trial, the classification of patients will be based on objective quantitative results of laboratory tests. It is expected the test performances will vary according to HIV status. Participants will be classified according to their experimental test results

Conditions

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Tuberculosis Hiv

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

This will be a phase III open randomised diagnostic trial.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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CRP and Xpert ULTRA MTB/RIF

Scheme 1 will screen all patients for HIV using rapid tests routinely used by the clinics and a rapid CRP. Patients with CRP \>10 will be further tested using Xpert ULTRA. Individuals with HIV will undergo an HIV VL using Xpert HIV-1 VL.

Group Type EXPERIMENTAL

CRP and Xpert ULTRA MTB/RIF

Intervention Type DIAGNOSTIC_TEST

A molecular assay to detect M tuberculosis DNA ULTRA is already endorsed by the WHO. However the tests are still considered experimental in Nigeria and Ethiopia.

standard test Xpert

Intervention Type DIAGNOSTIC_TEST

The investigators will use Xpert to compare its agreement with scheme 1 (CRP plus Truenat MTB) and scheme 2 (CRP plus ULTRA).

Culture as reference standard

Intervention Type DIAGNOSTIC_TEST

The investigators will use culture to assess the sensitivity of schemes 1 and 2

CRP and Molbio Truenat MTB

Scheme 2 will screen individuals for HIV and CRP (as in scheme 1) and patients with CRP \>10 will be tested using Molbio Truenat MTB. Individuals with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and individuals with Truenat MTB-positive samples wil be tested with Truenat MTB RIF.

Group Type EXPERIMENTAL

CRP and Molbio Truenat MTB

Intervention Type DIAGNOSTIC_TEST

A molecular assay to detect M tuberculosis DNA Truenat is currently undergoing the process of endorsement by the WHO.

standard test Xpert

Intervention Type DIAGNOSTIC_TEST

The investigators will use Xpert to compare its agreement with scheme 1 (CRP plus Truenat MTB) and scheme 2 (CRP plus ULTRA).

Culture as reference standard

Intervention Type DIAGNOSTIC_TEST

The investigators will use culture to assess the sensitivity of schemes 1 and 2

standard test Xpert

All patients receiving in scheme 1 and scheme 2 will be tested using the standard tests used in the study context. These are rapid HIV tests, Xpert MTB/RIF and culture.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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CRP and Molbio Truenat MTB

A molecular assay to detect M tuberculosis DNA Truenat is currently undergoing the process of endorsement by the WHO.

Intervention Type DIAGNOSTIC_TEST

CRP and Xpert ULTRA MTB/RIF

A molecular assay to detect M tuberculosis DNA ULTRA is already endorsed by the WHO. However the tests are still considered experimental in Nigeria and Ethiopia.

Intervention Type DIAGNOSTIC_TEST

standard test Xpert

The investigators will use Xpert to compare its agreement with scheme 1 (CRP plus Truenat MTB) and scheme 2 (CRP plus ULTRA).

Intervention Type DIAGNOSTIC_TEST

Culture as reference standard

The investigators will use culture to assess the sensitivity of schemes 1 and 2

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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CRP and Truelab MTB CRP and ULTRA

Eligibility Criteria

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Inclusion Criteria

1. Adult with presumptive TB
2. At least one of the following criteria: Cough \> 2-week duration, weight loss, unexplained fever, night sweats or haemoptysis.
3. Willing to participate in the study

Exclusion Criteria

1. Age unknown and likely being a minor (looks \<18 years old)
2. Known pregnancy
3. Has received or is receiving anti-TB treatment
4. Already diagnosed with TB.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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REACH Ethiopia

UNKNOWN

Sponsor Role collaborator

Bingham University

UNKNOWN

Sponsor Role collaborator

Liverpool School of Tropical Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Luis E Cuevas, Professor

Role: PRINCIPAL_INVESTIGATOR

Liverpool School of Tropical Medicine

Locations

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Zankli Research Centre

Kobape, Nasarawa State, Nigeria

Site Status

Countries

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Nigeria

References

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Inbaraj LR, Daniel J, Sathya Narayanan MK, Srinivasalu VA, Bhaskar A, Scandrett K, Rajendran P, Kirubakaran R, Shewade HD, Malaisamy M, Padmapriyadarsini C, Takwoingi Y. Truenat MTB assays for pulmonary tuberculosis and rifampicin resistance in adults and adolescents. Cochrane Database Syst Rev. 2025 Mar 24;3(3):CD015543. doi: 10.1002/14651858.CD015543.pub2.

Reference Type DERIVED
PMID: 40122135 (View on PubMed)

Other Identifiers

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18-063

Identifier Type: -

Identifier Source: org_study_id

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