Utility of Sputum Induction and Novel Technologies to Improve TB Diagnosis in a High HIV Prevalence Primary Care Setting (SINET)

University of Cape Town (UCT)

Status: Completed

Conditions: Tuberculosis

Treatments: Procedure: standard routine expectorated sputum; Procedure: Sputum induction

Study type: Interventional

Funder types: Other

Identifiers

NCT01545661

SINET study

Details and patient eligibility

About

This study will investigate the benefit of using Sputum induction for TB diagnosis in a primary care clinic for adult TB suspects that are either unable to produce a sputum sample (sputum scarce) or on initial diagnostic work-up have 2 negative sputum smear samples (WHO standard for frontline TB diagnosis). The investigators hypothesize that acquiring an induced sputum sample for smear microscopy and liquid TB culture will decrease time-to-diagnosis and time-to-treatment initiation in smear negative/sputum scarce TB patients in a primary care clinic in a resource-limited high TB HIV prevalent setting.

Full description

Tuberculosis is on the increase in Africa. A key area of weakness in TB control efforts is the inability to make a rapid diagnosis. This is, in part, due to the inability to obtain representative biological samples and the non-availability of cheap, effective, rapid and field-friendly diagnostic tools. Indeed, in HIV positive patients, where the sensitivity of sputum smear is as low as 20%, culture results take several weeks and a significant proportion of patients do not expectorate sputum. Sputum induction for the diagnosis of TB has been evaluated in several studies, has been shown to have a good yield, feasibility and safety when performed correctly, and with diagnostic comparability to bronchoscopy. Few studies have evaluated the performance of induced sputum outside of the hospital environment and the tolerability, yield and performance outcome of sputum induction in a primary care facility has yet to be evaluated. The objective of this study is two-fold. We seek to evaluate, through a randomized controlled trial, the feasibility, performance outcomes and impact on time-to-diagnosis and -treatment of sputum induction, in a high HIV prevalence primary care setting, for the diagnosis of smear negative/ sputum scarce TB. We hypothesize that acquiring an induced sputum sample for smear microscopy and liquid TB culture will decrease time-to-diagnosis and time-to-treatment initiation in smear negative/sputum scarce TB patients in a primary care clinic in a resource-limited high TB HIV prevalent setting. We will also evaluate the potential incremental benefit of novel technologies to improve the rapidity and diagnostic yield using induced sputum samples (Xpert MTB/RIF assay, microscopic observation drug susceptibility testing (MODS) and the Genotype MTB DRplus line probe assay).

Enrollment: 517 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 2x smear negative or sputum scarce TB suspects
2. Primary care patient (not referred by doctor)
3. Adult patients (>18 years)
4. Able to provide informed consent

Exclusion criteria

1. Not meeting inclusion criteria
2. <18 years
3. Unable to provide informed consent

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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517 participants in 2 patient groups

Sputum induction

Experimental group

Description:

Enrolled patients receive sputum induction (using ultrasonic nebulisation with hypertonic saline)

Treatment:

Procedure: Sputum induction

No sputum induction

Active Comparator group

Description:

Enrolled patients randomised to this study arm will receive an observed expectorated sputum collection attempt. Research nurses train study patients on the method of producing sputum spontaneously.

Treatment:

Procedure: standard routine expectorated sputum