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

NCT ID: NCT01693224

Last Updated: 2012-09-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 512 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-02-28

Brief Summary

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.

Detailed 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).

Conditions

Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Miliary

Keywords

Tests, Diagnostic; Mycobacterium tuberculosis; Mycobacterium tuberculosis antigens; TB; Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Miliary; Lipoarabinomannan

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

Alere "Determine" lateral-flow urine lipoarabinomannan assay

lateral-flow (point-of-care) urine test to detect the lipoarabinomannan (LAM) component of the M. tuberculosis antigen in the urine of TB suspects, in vitro.

Manufacturer: Alere

Intervention Type: DEVICE

Alere "Clearview" ELISA urine LAM assay

ELISA-based urine test to detect the lipoarabinomannan component of the M. tuberculosis antigen in the urine of TB suspects, in vitro.

Manufacturer: Alere.

Intervention Type: DEVICE

Cepheid Xpert MTB/Rif assay

Intervention Type: DEVICE

Other Intervention Names

Determine lateral-flow urine LAM TB test; Clearview ELISA urine LAM TB test; Cepheid Xpert MTB/Rif test

Eligibility Criteria

Inclusion Criteria

• 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cape Town

OTHER

Sponsor Role: collaborator

Tuberculosis Clinical Diagnostics Research Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan Dorman, MD

Role: STUDY_CHAIR

Johns Hopkins University

Mark Nicol, MBChB, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town, Faculty of Health Sciences, Dept. of Medical Microbiology, Cape Town, South Africa

Mischka Moodley, MBChB, DTM&H, FCPath(Micro)SA

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town, Faculty of Health Sciences, Dept. of Medical Microbiology, Cape Town, South Africa

Locations

G.F. Jooste Hospital

Cape Town, Western Cape, South Africa

Town Two Clinic

Cape Town, Western Cape, South Africa

Countries

South Africa

References

Nakiyingi L, Moodley VM, Manabe YC, Nicol MP, Holshouser M, Armstrong DT, Zemanay W, Sikhondze W, Mbabazi O, Nonyane BA, Shah M, Joloba ML, Alland D, Ellner JJ, Dorman SE. Diagnostic accuracy of a rapid urine lipoarabinomannan test for tuberculosis in HIV-infected adults. J Acquir Immune Defic Syndr. 2014 Jul 1;66(3):270-9. doi: 10.1097/QAI.0000000000000151.

Reference Type: DERIVED

PMID: 24675585 (View on PubMed)

Other Identifiers

NA_00043138

Identifier Type: OTHER

Identifier Source: secondary_id

DMID 10-0051

Identifier Type: -

Identifier Source: org_study_id