Clinical trial NCT01545661: Utility of Sputum Induction and Novel Technologies to Improve TB Diagnosis in a High HIV Prevalence Primary Care Setting
Official title: A Randomised Control Trial of Sputum Induction, and New and Emerging Technologies in a High HIV Prevalence Primary Care Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tuberculosis
Keywords: Tuberculosis
diagnosis
sputum induction
primary care
Lead sponsor: University of Cape Town
Sponsor class: OTHER
First posted: 2012-03-07
Enrollment: 517
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Time-to-treatment initiation
timeFrame: Up to 48 days after enrollment
Secondary outcomes:
measure: Diagnostic yield of sputum culture
timeFrame: Up to 2 months after enrollment
measure: Diagnostic yield and accuracy of sputum smear microscopy
timeFrame: Up to 2 months after enrollment
measure: Feasibility of sputum induction in primary care clinics
timeFrame: 2 years
measure: Safety and tolerability of sputum induction performed in primary care clinics
timeFrame: 2 years
measure: Diagnostic yield and accuracy of additional diagnostics including Xpert MTB/RIF assay, MODS and Genotype MTBDRplus
timeFrame: 2 years
measure: Cost-analysis of sputum induction for primary care clinics
timeFrame: 2 years
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: University of Cape Town
state: Western Cape
Study officials:
affiliation: University of Cape Town
name: Jonathan G Peter, MBChB
role: PRINCIPAL_INVESTIGATOR
References:
citation: Peter JG, Theron G, Pooran A, Thomas J, Pascoe M, Dheda K. Comparison of two methods for acquisition of sputum samples for diagnosis of suspected tuberculosis in smear-negative or sputum-scarce people: a randomised controlled trial. Lancet Respir Med. 2013 Aug;1(6):471-8. doi: 10.1016/S2213-2600(13)70120-6. Epub 2013 Jul 19.