Clinical trial NCT01693224: Feasibility of a Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in South Africa
Official title: Feasibility of Using the Inverness Lateral Flow Urine LAM Test for Diagnosis of Tuberculosis in HIV-Positive TB Suspects in Cape Town, South Africa
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Tuberculosis
Tuberculosis, Pulmonary
Tuberculosis, Miliary
Keywords: Tests, Diagnostic
Mycobacterium tuberculosis
Mycobacterium tuberculosis antigens
TB
Tuberculosis
Tuberculosis, Pulmonary
Tuberculosis, Miliary
Lipoarabinomannan
Lead sponsor: Tuberculosis Clinical Diagnostics Research Consortium
Sponsor class: NETWORK
Collaborators: name: University of Cape Town
First posted: 2012-09-26
Enrollment: 512
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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).

Eligibility 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.

Primary outcomes:
measure: Sensitivity of the lateral-flow urine LAM assay (LF-LAM)
timeFrame: One year
measure: Failure rate of the lateral-flow urine LAM assay
timeFrame: One year
measure: Inter-reader variability of the lateral-flow urine LAM assay
timeFrame: One year
measure: Specificity of the lateral-flow urine LAM assay (LF-LAM)
timeFrame: One year
Secondary outcomes:
measure: Sensitivity of the ELISA-based urine LAM test
timeFrame: One year
measure: Diagnostic yield (expressed as number of TB cases detected) of various diagnostic strategies (see description)
timeFrame: One year
measure: Time to diagnosis (expressed in days) of various diagnostic strategies (see description)
timeFrame: One year
measure: Accuracy, efficiency, costs, and cost-effectiveness of various combinations of TB diagnostic tests
timeFrame: One year
measure: Satisfaction of lateral-flow urine LAM test operators
timeFrame: One year
measure: Specificity (Sp) of the ELISA-based urine LAM test
timeFrame: One year
measure: Sensitivity of the Xpert MTB/Rif test to detect MTB in blood
timeFrame: One year
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: G.F. Jooste Hospital
state: Western Cape
city: Cape Town
country: South Africa
facility: Town Two Clinic
state: Western Cape
Study officials:
affiliation: Johns Hopkins University
name: Susan Dorman, MD
role: STUDY_CHAIR
affiliation: University of Cape Town, Faculty of Health Sciences, Dept. of Medical Microbiology, Cape Town, South Africa
name: Mark Nicol, MBChB, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cape Town, Faculty of Health Sciences, Dept. of Medical Microbiology, Cape Town, South Africa
name: Mischka Moodley, MBChB, DTM&H, FCPath(Micro)SA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.