Plain English Summary
Background and study aims
Sub-Saharan Africa bears the brunt of the global HIV/AIDS epidemic and tuberculosis (TB) is the leading cause of AIDS-related illness and deaths worldwide. Studies from across the continent have shown that between one-and two-thirds of HIV-infected adult hospital in-patients who die have evidence of TB at post-mortem. Much of this disease is neither clinically suspected nor diagnosed before death. This indicates a failure of current approaches to diagnosis, which is the key problem addressed by this trial. We believe that recent advances in TB diagnosis can be harnessed to address this challenge in a fundamentally new way. Studies in South Africa have found that the number of HIV-infected patients confirmed to have TB needing to be admitted to hospital was extremely high (32%). However, they also found symptoms were a poor predictor of the disease and that, in day-to-day clinical practice, many cases are not diagnosed. We propose that, regardless of symptoms, all such patients should be investigated for TB on admission. In these studies the number of patients diagnosed using the traditional approach of sputum-based testing was limited as fewer than half of the patients could produce sputum samples, and also because much of the disease involved organs other than the lungs. In contrast, urine samples could be obtained from almost all patients and testing these with rapid diagnostics (a simple 30-minute 'dipstick' test, Determine TB-LAM Ag test, and the recently WHO-approved Xpert MTB/RIF test) increased the number of early diagnoses of TB substantially. The aim of this study is find out whether we can reduce the number of early deaths by screening all HIV-infected patients admitted to medical wards in hospital using these rapid urine-based tests.
Who can participate?
Adult HIV-infected medical inpatients admitted to two regional referral hospitals in South Africa and Malawi.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 (control) are screened for TB using the Xpert testing of sputum (the current 'standard' care according to guidelines). Those in group 2 (intervention) also undergo Xpert testing and also additional screening with a combination of the two urine-based diagnostic tests. The care of patients provided by the routine medical team is not otherwise altered. The results are analysed to see whether the additional urine-based screening results in greater patient survival due to an increase in number and early diagnosis of TB.
What are the possible benefits and risks of participating?
We anticipate that patients in the intervention group with HIV-associated TB will benefit from urine-based screening due to an increased number being diagnosed or being diagnosed early, and being given early treatment. However we cannot guarantee any benefits from this study. Risk of harm to patients in this study is low. The study requirement for samples of blood, sputum and urine from patients is not associated with any risks to patient safety. However, it is possible that such screening may inadvertently be harmful in the following ways: a very small proportion of screening tests may give false-positive results, leading to inappropriate treatment for TB (anticipated to be less than 1 per 100) or for MDR-TB, rapid TB diagnosis may result in other concurrent pathologies being overlooked or reduce the likelihood that patients receive a course of simple antibiotics as part of the diagnostic work-up.
Where is the study run from?
The Zomba Central Hospital (Malawi) and Edendale Regional Hospital (South Africa)
When is the study starting and how long is it expected to run for?
February 2015 to January 2018
Who is funding the study?
Global Health Trials (Wellcome Trust, the UK Department for International Development and the UK Medical Research Council)
Who is the main contact?
Dr Katherine Fielding
Trial website
Contact information
Type
Scientific
Primary contact
Dr Katherine Fielding
ORCID ID
Contact details
London School of Hygiene & Tropical Medicine
Department of Infectious Disease Epidemiology
Keppel Street
London
WC1E 7HT
United Kingdom
+44 (0)207 927 2889
Katherine.Fielding@lshtm.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
LOI:13.016 / pFACT6451 / ITCRZE64
Study information
Scientific title
Rapid urine-based Screening for Tuberculosis to reduce AIDS-related Mortality in hospitalized Patients in Africa (STAMP): a pragmatic, multicentre, individually randomized clinical trial
Acronym
STAMP
Study hypothesis
The implementation of a rapid, sensitive urine-based screening strategy for TB, used in combination with routine sputum-based standard of care diagnosis, can reduce all-cause mortality among HIV-infected medical in-patients newly admitted to hospitals in southern African countries.
Ethics approval
1. London School of Hygiene & Tropical Medicine Research Ethics Committee, 05/05/2015, ref: 9630
2. College of Medicine Research Ethics Committee (Malawi), 03/08/2015, ref: P.06/15/1743
3. University of KwaZulu-Natal Biomedical Research Ethics Committee (South Africa), 09/09/2015, ref: BFC215/15
Study design
Pragmatic multicentre individually randomized clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
HIV-associated tuberculosis
Intervention
A screening strategy for HIV-infected adult patients requiring acute admission to hospital medical wards, based on testing of urine with the Determine TB-LAM lateral-flow assay and Xpert MTB/RIF assay and testing of sputum with Xpert MTB/RIF assay (intervention arm). This will be compared to sputum testing alone (standard of care arm).
Intervention type
Procedure/Surgery
Phase
Drug names
Primary outcome measure
Risk of all-cause mortality at 56 days after randomization from any cause, compared between arms.
Secondary outcome measures
1. Time to all-cause mortality
2. Proportions of patients with:
2.1. Microbiologically confirmed diagnosis of TB
2.2. Clinically diagnosed TB disease
3. Time from randomisation to:
3.1. TB diagnosis
3.2. Start of TB treatment in days
4. Proportion of patients receiving:
4.1. Antibacterial treatment
4.2. In ART naïve patients, proportion starting ART and time to ART initiation in days
5.1. Duration of hospital stay in days
5.2. Cumulative incidence of hospital readmission (c) cumulative incidence of loss to follow-up
All measured at 56 days after randomization
Overall trial start date
01/02/2015
Overall trial end date
31/01/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Requires acute admission to a hospital medical ward
2. Have confirmed HIV-infection
3. Willing and able to provide informed consent
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
2600
Participant exclusion criteria
1. Aged <18 years
2. Has been admitted to a medical ward for longer than 48 hours
3. Has received treatment for TB within the preceding 12 months, or has received isoniazid preventative therapy (IPT) within the last 6 months
4. Residence does not lie within a pre-defined geographic area or plans to leave this area during the period of trial follow-up
5. Unable or unwilling to provide informed consent
Recruitment start date
01/09/2015
Recruitment end date
31/07/2017
Locations
Countries of recruitment
Malawi, South Africa
Trial participating centre
Zomba Central Hospital
-
Malawi
Trial participating centre
Edendale Regional Hospital
-
South Africa
Sponsor information
Organisation
London School of Hygiene & Tropical Medicine
Sponsor details
Clinical Trials Unit
Keppel Street
London
WC1E 7HT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Charity
Funder name
Wellcome Trust
Alternative name(s)
Wellcome
Funding Body Type
private sector organisation
Funding Body Subtype
international
Location
United Kingdom
Funder name
Department for International Development
Alternative name(s)
Department for International Development, UK, DFID
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Funder name
Medical Research Council
Alternative name(s)
MRC
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Study results will be disseminated to relevant local, national and international policymakers and will also be rapidly made available through presentations at relevant international conferences and regional conferences in southern Africa. The main trial results will be published in an appropriate peer-reviewed scientific journal as soon as possible following completion of the trial and analysis of the results.
Intention to publish date
31/01/2019
Participant level data
Available on request
Basic results (scientific)
Publication list
2016 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/27659507
2018 results in: https://www.ncbi.nlm.nih.gov/pubmed/30032978