Condition category
Infections and Infestations
Date applied
03/07/2019
Date assigned
02/09/2019
Last edited
05/09/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Tuberculosis (TB) is a major cause of morbidity and mortality worldwide and early diagnosis is key to reducing this high disease burden. The Xpert MTB/RIF assay (GeneXpert) is a rapid test for diagnosing TB which was endorsed by WHO in 2010. An improved version of the Xpert MTB/RIF, the Xpert MTB/RIF Ultra (Xpert Ultra), is now available. However, little evidence exists for the impact of Xpert Ultra on clinical outcomes among ambulatory patients in high HIV and TB burden settings. Digital radiography machines designed as portable systems with better image quality are now available. Their availability has led to renewed interest in their inclusion in the TB diagnostic pathway. The aim of this study is to find out whether the use of Xpert Ultra in HIV-positive patients attending antiretroviral (ART) clinics can increase diagnostic yield and treatment initiation, and potentially reduce the number of deaths.

Who can participate?
Patients aged 18 and over attending antiretroviral therapy (ART) clinics at Bangwe health centre and Queen Elizabeth Central Hospital (QECH) and presenting with symptoms of TB

What does the study involve?
Participants are randomly allocated to one of four groups. Participants are requested to submit two sputum samples and depending on their group, the samples are analysed with Xpert Ultra or available standard of care test (GeneXpert or microscopy). Participants are also requested to undergo chest radiography depending on their group. All participants are followed up after 28 and 56 days for TB treatment initiation and vital status.

What are the possible benefits and risks of participating?
The benefit of this study is that participants will find out whether they have TB or not and have the opportunity to start TB treatment. The study is also beneficial to healthcare providers because it will show how effective these new TB diagnostic tests are.

Where is the study run from?
1. Queen Elizabeth Central Hospital (Malawi)
2. Bangwe Health Centre (Malawi)

When is the study starting and how long is it expected to run for?
June 2018 to August 2021

Who is funding the study?
1. Helse Nord Tuberculosis Initiative
2. Foundation for Innovative New Diagnostics (FIND)

Who is the main contact?
1. Dr Marriot Nliwasa
mnliwasa@medcol.mw
2. Dr Madalo Mukoka
mmukoka@medcol.mw

Trial website

Contact information

Type

Scientific

Primary contact

Dr Marriot Nliwasa

ORCID ID

Contact details

College of Medicine
Private bag 360
Blantyre
Blantyre
Private 360
Malawi
+265 (0)888 681 948
mnliwasa@medcol.mw

Type

Public

Additional contact

Dr Madalo Mukoka

ORCID ID

Contact details

College of Medicine
Private bag 360
Blantyre
Blantyre
Private bag 360
Malawi
+265 (0)888 518 464
mmukoka@medcol.mw

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

Nil known

Study information

Scientific title

Utility of the Xpert® MTB/RIF Ultra assay with the GeneXpert®Omni System and digital chest radiography for diagnosis of tuberculosis in high HIV prevalence settings: protocol for a randomised control trial

Acronym

FIND EXACT-TB

Study hypothesis

The use of Xpert Ultra in HIV-positive patients attending antiretroviral (ART) clinics can increase diagnostic yield and treatment initiation, and could potentially reduce mortality.

Ethics approval

Approval pending, College of Medicine Research Ethics Committee (COMREC) (College of Medicine, Private Bag 360, Blantyre, Malawi, Email: comrec@medcol.mw), ref: P.05/17/2175

Study design

Pragmatic multi-site individually-randomized controlled trial with a 2 by 2 factorial design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format

Condition

Tuberculosis

Intervention

A random allocation sequence will be generated in advance using computer-generated random numbers. This will be done by the study statistician. Randomisation will be 1:1 to the four arms of the trial and block randomised with a variable block size. Paper slips with a randomisation number will be printed and inserted and sealed in an opaque envelope. The envelopes will be kept by the study statistician and distributed consecutively to the research assistants on the enrolment of the participant. The envelope will only contain information of allocation to chest radiography. That is to say research assistants and clinicians will know if participants will have to be referred for a chest x-ray or not. As specified in each arm, chest radiography results will be offered to the responsible clinicians to help guide TB treatment. Randomisation to Xpert Ultra will only be known by the laboratory technicians (the research team and responsible clinicians will be masked to the sputum screening arm allocation).

Participants will be requested to submit two sputum samples and depending on study arm, the samples will be analysed with Xpert Ultra or available standard of care test (GeneXpert or microscopy). Participants will also be requested to undergo chest radiography depending on study arm. All participants will be followed up at 28 days and 56 days for TB treatment initiation and vital status.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Proportion of patients initiating TB treatment within 28 days of enrolment compared between standard of care Xpert and Xpert Ultra arms

Secondary outcome measures

1. Proportion of patients diagnosed with TB initiating TB treatment within 28 days of enrolment between Standard Of Care and Xpert Ultra arms
2. Time from enrolment to TB treatment initiation between Standard Of Care and Xpert Ultra arms
3. All-cause mortality risk between Standard Of Care and Xpert Ultra arms
4. Proportion of patients diagnosed with bacteriologically-confirmed TB initiating TB treatment within 28 days of enrolment between chest radiography and no chest radiography arms

Overall trial start date

01/06/2018

Overall trial end date

01/08/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Aged ≥ 18 years
2. Having TB symptoms (cough of any duration, fever, night sweats or weight loss)
3. Able to submit sputum
4. Willing and able to provide informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

1252

Participant exclusion criteria

1, Presence of clinical danger signs (unable to walk unaided, confused or agitated, breathless when speaking or at rest)
2. Already taking TB treatment, or taken TB treatment within the last 60 days
3. Unable to submit sputum and refuses offer of sputum induction
4. Previously been enrolled in the trial

Recruitment start date

02/09/2019

Recruitment end date

31/01/2021

Locations

Countries of recruitment

Malawi

Trial participating centre

Queen Elizabeth Central Hospital
PO Box 95
Blantyre
PO Box 95
Malawi

Trial participating centre

Bangwe Health Centre
Private Bag 66
Blantyre
Private bag 66
Malawi

Sponsor information

Organisation

London School of Hygiene and Tropical Medicine

Sponsor details

Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)20 7636 8636
comms@lshtm.ac.uk

Sponsor type

University/education

Website

http://www.lshtm.ac.uk

Funders

Funder type

Research organisation

Funder name

Helse Nord Tuberculosis Initiative

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Foundation for Innovative New Diagnostics (FIND)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results of this trial will be disseminated to relevant local and international conferences. The main local conference is the annual Malawi College of Medicine research dissemination conference and the target international conference is the annual Union World Conference on Lung Health. The results of this trial will be submitted for publication in open access, medical journals. The researchers will give frequent updates to the consultants working in the medical department at the Queen Elizabeth Central Hospital.

IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Marriot Nliwasa (mnliwasa@medcol.mw) and Dr Madalo Mukoka- mmukoka@medcol.mw. Individual-level data will be available at the time of publishing and will be shared together with the publication. The researchers will make a GitHub repository which allows access to the datasets and allows replication of the analyses. Consent will be sought from the patients and all data will be anonymized. There are no ethical or legal restrictions.

Intention to publish date

01/05/2021

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

05/09/2019: Internal review. 05/07/2019: Trial's existence confirmed by ethics committee.