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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Jonathan Peter, University of Cape Town
ClinicalTrials.gov Identifier:
NCT01545661
First received: July 7, 2011
Last updated: December 21, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention
Tuberculosis
Procedure: Sputum induction
Procedure: standard routine expectorated sputum

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: A Randomised Control Trial of Sputum Induction, and New and Emerging Technologies in a High HIV Prevalence Primary Care Setting

Resource links provided by NLM:


Further study details as provided by University of Cape Town:

Primary Outcome Measures:
  • Time-to-treatment initiation [ Time Frame: Up to 48 days after enrollment ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Diagnostic yield of sputum culture [ Time Frame: Up to 2 months after enrollment ] [ Designated as safety issue: No ]

    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.


  • Diagnostic yield and accuracy of sputum smear microscopy [ Time Frame: Up to 2 months after enrollment ] [ Designated as safety issue: No ]

    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


  • Feasibility of sputum induction in primary care clinics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Feasibility and robustness of performing sputum induction in primary care clinics (measures include - sputum induction failure rates, turn-around-time, user appraisals and evaluation)

  • Safety and tolerability of sputum induction performed in primary care clinics [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Side-effects of sputum induction procedures Number of induced sputum procedures terminated because of patient side-effects and safety

  • Diagnostic yield and accuracy of additional diagnostics including Xpert MTB/RIF assay, MODS and Genotype MTBDRplus [ Time Frame: 2 years ] [ Designated as safety issue: No ]

    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.


  • Cost-analysis of sputum induction for primary care clinics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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


Enrollment: 517
Study Start Date: August 2009
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sputum induction
Enrolled patients receive sputum induction (using ultrasonic nebulisation with hypertonic saline)
Procedure: Sputum induction
Ultrasonic nebulisation 3% hypertonic saline nebulised for duration of 20 mins
Active Comparator: No sputum induction
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.
Procedure: 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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01545661

Locations
South Africa
University of Cape Town
Cape Town, Western Cape, South Africa, 7945
Sponsors and Collaborators
University of Cape Town
Investigators
Principal Investigator: Jonathan G Peter, MBChB University of Cape Town
  More Information

No publications provided

Responsible Party: Jonathan Peter, Dr, University of Cape Town
ClinicalTrials.gov Identifier: NCT01545661     History of Changes
Other Study ID Numbers: SINET study
Study First Received: July 7, 2011
Last Updated: December 21, 2012
Health Authority: South Africa: Human Research Ethics Committee

Keywords provided by University of Cape Town:
Tuberculosis
diagnosis
sputum induction
primary care

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 21, 2014