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

Tuberculosis Clinical Trial

— SINET  

Official title:

A Randomised Control Trial of Sputum Induction, and New and Emerging Technologies in a High HIV Prevalence Primary Care Setting

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01545661
• Other study ID #: SINET study
• Status: Completed
• Phase: N/A
• First received: July 7, 2011
• Last updated: December 21, 2012
• Start date: August 2009
• Est. completion date: May 2012

Study information

• Verified date: December 2012
• Source: University of Cape Town
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Human Research Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 517
• Est. completion date: May 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Tuberculosis

Intervention

Procedure:
• Sputum induction
Ultrasonic nebulisation 3% hypertonic saline nebulised for duration of 20 mins
• standard routine expectorated sputum
Patients in the control group are trained by the research staff to produce sputum but no device is utilized. Sputum is spontaneously expectorated where possible

Locations

Country	Name	City	State
South Africa	University of Cape Town	Cape Town	Western Cape

Sponsors (1)

Lead Sponsor	Collaborator
University of Cape Town

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-to-treatment initiation	Time-specific proportion of patients initiated on TB treatment between study arms Time-points to be analysed include 3, 5, 7, 10, 14, 21, 48 days from enrollment.	Up to 48 days after enrollment	No
Secondary	Diagnostic yield of sputum culture	Difference in diagnostic yield of a single sputum TB culture between study arms.; This will compare the single induced or expectorated sputum sample collected at study enrollment.	Up to 2 months after enrollment	No
Secondary	Diagnostic yield and accuracy of sputum smear microscopy	Difference in diagnostic yield and accuracy of a single sputum TB smear between study arms.; This will compare the single induced or expectorated sputum sample collected at study enrollment.; Liquid TB culture will be used as the reference standard for assessment of diagnostic accuracy Fluorescence smear microscopy will be performed on auramine-O stained concentrated samples	Up to 2 months after enrollment	No
Secondary	Feasibility of sputum induction in primary care clinics	Feasibility and robustness of performing sputum induction in primary care clinics (measures include - sputum induction failure rates, turn-around-time, user appraisals and evaluation)	2 years	No
Secondary	Safety and tolerability of sputum induction performed in primary care clinics	Side-effects of sputum induction procedures Number of induced sputum procedures terminated because of patient side-effects and safety	2 years	Yes
Secondary	Diagnostic yield and accuracy of additional diagnostics including Xpert MTB/RIF assay, MODS and Genotype MTBDRplus	Difference in diagnostic yield and accuracy of Xpert MTB/RIF, MODS liquid culture and the Genotype MTBDRplus on a single induced or expectorated sputum sample collected at enrollment.; Liquid TB culture will be used as the reference standard for diagnostic accuracy measures.	2 years	No
Secondary	Cost-analysis of sputum induction for primary care clinics	Based on diagnostic accuracy measures of different diagnostic tests between the induced sputum and standard care groups, cost-of-diagnosis will be calculated and compared	2 years	No