Impact of a novel molecular tuberculosis (TB) diagnostic system in patients at high risk of TB mortality in rural South Africa

ISRCTN	ISRCTN18642314
DOI	https://doi.org/10.1186/ISRCTN18642314
Protocol serial number	Wellcome Trust grant number 090999/Z/09/Z, South African National Clinical Trials Registry DOH-27-0711-3568
Sponsor	London School of Hygiene and Tropical Medicine (UK)
Funder	Wellcome Trust (UK) (090999/Z/09/Z)

Submission date: 15/06/2011
Registration date: 17/06/2011
Last edited: 25/07/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
HIV and tuberculosis (TB) infections are the leading causes of death for young adults in South Africa. TB bacteria that have developed resistance to first-line TB drugs (multidrug-resistant TB or MDR-TB) are now causing significant numbers of deaths. Diagnosis of MDR-TB is a laborious process which can take two to three months, by which time up to half of those with MDR-TB will have died. The Xpert MTB/RIF system is a new diagnostic test which can identify TB and can also recognise whether or not there is drug resistance within two hours. Hlabisa sub-district in KwaZulu-Natal is one place where MDR-TB has become very common in association with high levels of HIV infection. This study aims to investigate the impact of the Xpert MTB/RIF system, specifically whether outcomes are different when the system is positioned at different levels of the health system.

Who can participate?
Patients aged 18 or older with suspected TB, who have a confirmed HIV infection and/or are at high risk for MDR-TB

What does the study involve?
Participants are randomly allocated to one of two strategies: Xpert MTB/RIF testing at a district hospital laboratory or Xpert MTB/RIF testing at a primary health care clinic (point-of-care). The number of TB patients starting appropriate treatment within 30 days, the time taken to start TB treatment, and the number of deaths and hospital admissions in first 60 days are all measured.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Africa Centre for Health and Population Studies (South Africa)

When is the study starting and how long is it expected to run for?
July 2011 to December 2012

Who is funding the study?
Wellcome Trust (UK)

Who is the main contact?
Dr Richard Lessells
rlessells@africacentre.ac.za

Contact information

Dr Richard Lessells
Scientific

Africa Centre for Health and Population Studies
PO Box 198
Mtubatuba
3935
South Africa

Phone	+27 (0)35 550 7500
Email	rlessells@africacentre.ac.za

Study information

Primary study design	Interventional
Study design	Single-centre cluster randomised controlled trial
Secondary study design	Cluster randomised trial
Study type	Participant information sheet
Scientific title	Impact of a novel molecular tuberculosis (TB) diagnostic system in patients at high risk of TB mortality in rural South Africa: a pragmatic cluster randomised controlled trial
Study objectives	Timely initiation of appropriate tuberculosis (TB) treatment will be improved when the diagnostic system is positioned at the primary health care clinic (point-of-care) compared to when it is positioned centrally at the district hospital laboratory.
Ethics approval(s)	1. University of KwaZulu-Natal Biomedical Research Ethics Committee, ref: BF033/11 2. London School of Hygiene and Tropical Medicine Ethics Committee, ref: 5926 Approval pending as of 15/06/2011
Health condition(s) or problem(s) studied	Pulmonary tuberculosis
Intervention	Comparison between two delivery strategies for the GeneXpert system and Xpert MTB/RIF test: Positioning at district hospital vs positioning at primary health care clinic
Intervention type	Other
Primary outcome measure(s)	Proportion of TB cases initiated on appropriate TB treatment within 30 days of enrolment
Key secondary outcome measure(s)	1. Time to initiation of appropriate TB treatment 2. Time to initiation of appropriate MDR-TB treatment 3. All-cause mortality at 60 days 4. Hospital admissions in first 60 days 5. Time to initiation of antiretroviral therapy (for eligible HIV-infected participants)
Completion date	31/12/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	2000
Key inclusion criteria	1. TB suspect (defined as cough of any duration) 2. Age 18 years or older 3. Confirmed human immunodeficiency virus (HIV) infection and/or high risk for multi-drug-resistant tuberculosis (MDR-TB)
Key exclusion criteria	1. Severely unwell requiring admission to hospital 2. Previous MDR/extensively drug-resistant tuberculosis (XDR-TB) diagnosis or treatment 3. Diagnosis or suspicion of extra-pulmonary TB only 4. Unable to give informed consent
Date of first enrolment	04/07/2011
Date of final enrolment	31/12/2012

Locations

Countries of recruitment

South Africa

Study participating centre

Africa Centre for Health and Population Studies

Mtubatuba
3935
South Africa

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2017		Yes	No
Protocol article	protocol	12/06/2013		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

25/07/2017: Publication reference added.
12/09/2016: Plain English summary added.