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

NCT04043390 | Completed

• 1 other identifier: 18-063
• Study Type: interventional
• Target: 1,100
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are suitable at the point-of-care;
2. 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. 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
4. 4.Assess the performance of two diagnostic schemes for the diagnosis of TB when compared to culture.
5. 5.Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to Xpert and
6. 6.Assess the cost of the two diagnostic schemes compared to Xpert.

Conditions

Tuberculosis; Hiv

Keywords

Xpert MTB/RIF; tuberculosis; diagnostics; Xpert Ultra; Truenat MTB; Truenat MTB RIF; C Reactive Protein; Xpert HIV-1 VL; Truenat HIV-1 VL; C Reactive Protein QUBE

Outcome Measures

Primary Outcomes (1)

• Performance of two diagnostic schemes for the diagnosis of TB when compared to culture.

  Sensitivity, specificity, positive and negative predictive values of schemes 1 and 2 to identify patients with TB. Culture will used as the reference standard.

  "up to two months", once culture results become available

Secondary Outcomes (3)

• Agreement of two diagnostic schemes for the diagnosis of TB when compared to Xpert.

  "up to two months", once culture results become available

• Time required for diagnosis of the two diagnostic schemes compared to Xpert.

  10 months

• Cost required for diagnosis of the two diagnostic schemes compared to Xpert.

  10 months

Study Arms (3)

CRP and Xpert ULTRA MTB/RIF

EXPERIMENTAL

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.

Diagnostic Test: CRP and Xpert ULTRA MTB/RIF; Diagnostic Test: standard test Xpert; Diagnostic Test: Culture as reference standard

CRP and Molbio Truenat MTB

EXPERIMENTAL

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.

Diagnostic Test: CRP and Molbio Truenat MTB; Diagnostic Test: standard test Xpert; Diagnostic Test: Culture as reference standard

standard test Xpert

NO INTERVENTION

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.

Interventions

CRP and Molbio Truenat MTB DIAGNOSTIC_TEST

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

Also known as: CRP and Truelab MTB

CRP and Molbio Truenat MTB

CRP and Xpert ULTRA MTB/RIF 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.

Also known as: CRP and ULTRA

CRP and Xpert ULTRA MTB/RIF

standard test Xpert DIAGNOSTIC_TEST

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

CRP and Molbio Truenat MTB; CRP and Xpert ULTRA MTB/RIF

Culture as reference standard DIAGNOSTIC_TEST

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

CRP and Molbio Truenat MTB; CRP and Xpert ULTRA MTB/RIF

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Liverpool School of Tropical Medicine: lead
• REACH Ethiopia: collaborator
• Bingham University: collaborator

Study Sites (1)

Zankli Research Centre

Kobape, Nasarawa State, P.M.B 005, Nigeria

Location

Related Publications (1)

• 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.

  PMID: 40122135 DERIVED

MeSH Terms

Conditions

Tuberculosis; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Luis E Cuevas, Professor

  Liverpool School of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a phase III open randomised diagnostic trial.

Study Record Dates

• First Submitted: December 19, 2018
• First Posted: August 2, 2019
• Study Start: January 21, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

NG (1)