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Feasibility of a Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in South Africa

T

Tuberculosis Clinical Diagnostics Research Consortium

Status

Unknown

Conditions

Tuberculosis
Tuberculosis, Miliary
Tuberculosis, Pulmonary

Treatments

Device: Alere "Determine" lateral-flow urine lipoarabinomannan assay
Device: Alere "Clearview" ELISA urine LAM assay
Device: Cepheid Xpert MTB/Rif assay

Study type

Interventional

Funder types

Other
NETWORK

Identifiers

NCT01693224
DMID 10-0051
NA_00043138 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting tuberculosis in HIV-infected adults.

A secondary study objective is to evaluate the accuracy and diagnostic yield of the Cepheid Xpert MTB/Rif test in detecting tuberculosis in the blood of HIV-infected adults.

Full description

Background: Tuberculosis (TB) incidence and mortality have increased dramatically as a result of the HIV epidemic. In parts of sub-Saharan Africa, TB is the leading cause of death among HIV-infected patients and approximately 50% of TB patients are HIV co-infected. Early treatment of TB is hindered by the lack of rapid, accurate diagnostic modalities that can be applied in resource-constrained settings. Mycobacterial culture is the laboratory standard for diagnosis of active TB, but it is costly, requires access to specialized laboratories, and takes weeks to provide results. Sputum smear microscopy detects less than half of HIV-infected TB cases in many settings. The Global Plan to Stop TB has prioritized the development of simple, accurate, inexpensive tests for TB case detection in HIV-positive individuals.

LAM: As a strategy for rapid TB diagnosis, the detection of Mycobacterium tuberculosis antigens has been explored over several decades. Lipoarabinomannan (LAM), a glycolipid component of the outer cell wall of mycobacteria, is an attractive diagnostic target for several reasons: it is heat-stable; cleared by the kidney; detectable in urine; and as a bacterial product, has the theoretical potential to discriminate active TB from latent TB infection independent of human immune responses. A urine test could facilitate TB diagnosis in patients in whom sputum is uninformative or not obtainable, and lacks the infection-control risks associated with sputum production or blood collection. Urine LAM detection may be amenable to simple, rapid, inexpensive point-of-care platforms.

This is a prospective study to evaluate the accuracy, diagnostic yield, operational performance, and time to diagnosis of a novel lateral-flow urine LAM test in detecting tuberculosis in HIV-infected adults. HIV-positive adults suspected to have TB will be enrolled after providing informed consent. Urine will be obtained for testing using the novel lateral flow urine LAM assay and an existing ELISA-based urine LAM assay. Conventional microbiological tests for TB and chest x-rays will also be performed. These tests will be performed on all participants enrolled (target sample size = 500).

A secondary study objective is to determine the accuracy and diagnostic yield of the Cepheid Xpert MTB/Rif test in detecting tuberculosis in the blood of HIV-infected adults (the same set of participants on whom the LAM testing is done; approximate sample size = 500).

Enrollment

512 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria (Individuals must meet all of the following inclusion criteria in order to be eligible to participate):

  • Informed consent

  • Suspected active tuberculosis

  • Willingness and ability to comply with study procedures

  • Any one or more of the following:

    • Current cough
    • Fever at any time within the preceding 4 weeks
    • Night sweats at any time within the preceding 4 weeks
    • Weight loss within the preceding 4 weeks
  • HIV-positive based on any one or more of the following:

    • written results of a positive HIV antibody test, and/or
    • written results of a positive HIV viral load, and/or
    • documentation in the medical record of positive HIV status by a treating clinician.

Exclusion Criteria (Any subjects meeting any of the following exclusion criteria at baseline will be excluded from study participation):

  • Multidrug tuberculosis treatment for greater than two days within the previous 60 days
  • Unwillingness or inability to provide a urine sample
  • Known chronic pulmonary condition, e.g. asthma, chronic obstructive pulmonary disease, emphysema
  • Respiratory distress, defined as respiratory rate of >30 or oxygen saturation <90%
  • Any specific condition that in the judgment of the investigator precludes participation because it could affect a subject's safety.

Trial design

Primary purpose

Diagnostic

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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