TuberculosisSINETNCT01545661
Utility of Sputum Induction and Novel Technologies to Improve TB Diagnosis in a High HIV Prevalence Primary Care Setting
A study testing Sputum induction and standard routine expectorated sputum in people with Tuberculosis, run by University of Cape Town at 1 site in South Africa.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Sputum induction and standard routine expectorated sputum
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 517 participants
- Where
- 1 siteSouth Africa
- Study dates
- Aug 2009to May 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 2x smear negative or sputum scarce TB suspects
- Primary care patient (not referred by doctor)
- Adult patients (>18 years)
- Able to provide informed consent
Who cannot join
- Not meeting inclusion criteria
- <18 years
- Unable to provide informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomised Control Trial of Sputum Induction, and New and Emerging Technologies in a High HIV Prevalence Primary Care Setting
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.
Read the 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).
- Conditions
- Tuberculosis
- Being tested
- Sputum induction, standard routine expectorated sputum
- Keywords
- Tuberculosis, diagnosis, sputum induction, primary care
- Medical subject headings
- Tuberculosis, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sputum inductionProcedure or surgery
Ultrasonic nebulisation 3% hypertonic saline nebulised for duration of 20 mins
standard routine expectorated sputumProcedure or surgery
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
| Study group | Role | What they receive |
|---|---|---|
| Sputum induction | Experimental | Enrolled patients receive sputum induction (using ultrasonic nebulisation with hypertonic saline) Receives: Procedure: Sputum induction |
| No sputum induction | Active comparator | 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. Receives: Procedure: standard routine expectorated sputum |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 48 days after enrollment
Secondary outcomes (6)
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.
Measured: Up to 2 months after enrollment
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
Measured: Up to 2 months after enrollment
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)
Measured: 2 years
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
Measured: 2 years
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.
Measured: 2 years
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2012 (estimated)
- Study startAug 2009
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 517 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cape Town
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jonathan Peter, University of Cape Town
- Investigators
- Jonathan G Peter, MBChB, Principal investigator, University of Cape Town
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01545661
- Sponsor's protocol ID
- SINET study
- Acronym
- SINET
- Status last verified
- Dec 2012
- First submitted
- 7 Jul 2011
- Last updated
- 24 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24429245
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Control Trial of Sputum Induction, and New and Emerging Technologies in a High HIV Prevalence Primary Care Setting
- ClinicalTrials.gov ID
- NCT01545661
- Acronym / sponsor ID
- SINET / SINET study
- Conditions
- Tuberculosis
- Keywords
- Tuberculosis, diagnosis, sputum induction, primary care
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 517 participants (actual)
- Lead sponsor
- University of Cape TownUniversity, hospital or other
- Study start
- Aug 2009
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 7 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sputum induction | Experimental | Procedure: Sputum inductionEnrolled patients receive sputum induction (using ultrasonic nebulisation with hypertonic saline) |
| No sputum induction | Active comparator | Procedure: standard routine expectorated sputumEnrolled 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 2x smear negative or sputum scarce TB suspects
- Primary care patient (not referred by doctor)
- Adult patients (>18 years)
- Able to provide informed consent
Key exclusion criteria (3 listed)
- Not meeting inclusion criteria
- <18 years
- Unable to provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sputum inductionUltrasonic nebulisation 3% hypertonic saline nebulised for duration of 20 mins | Procedure or surgery | Sputum induction |
| standard routine expectorated sputumPatients in the control group are trained by the research staff to produce sputum but no device is utilized. Sputum is spontaneously expectorated where possible | Procedure or surgery | No sputum induction |
Primary outcome
Time-to-treatment initiation
Time frame: Up to 48 days after enrollment
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.
6 secondary outcomes
Diagnostic yield of sputum culture
Time frame: Up to 2 months after enrollment
Diagnostic yield and accuracy of sputum smear microscopy
Time frame: Up to 2 months after enrollment
Feasibility of sputum induction in primary care clinics
Time frame: 2 years
Safety and tolerability of sputum induction performed in primary care clinics
Time frame: 2 years
Diagnostic yield and accuracy of additional diagnostics including Xpert MTB/RIF assay, MODS and Genotype MTBDRplus
Time frame: 2 years
Cost-analysis of sputum induction for primary care clinics
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2012.
- Derived from this study: PubMed 24429245Peter 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan G Peter, MBChB principal investigator
University of Cape Town
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sputum induction and standard routine expectorated sputum in people with Tuberculosis, run by University of Cape Town at 1 site in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-treatment initiation (time frame: Up to 48 days after enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01545661, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2012.