Condition category
Infections and Infestations
Date applied
22/04/2015
Date assigned
08/05/2015
Last edited
24/11/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

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
+44 207 927 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 measures

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

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

http://www.lshtm.ac.uk

Funders

Funder type

Charity

Funder name

Wellcome Trust

Alternative name(s)

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

private sector organisation

Funding Body Subtype

other non-profit

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

Results - basic reporting

Publication summary

2016 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/27659507

Publication citations

Additional files

Editorial Notes

24/11/2016: The study contact has been updated from Prof Stephen Lawn to Dr Katherine Fielding. In addition, the ethical approvals from Malawi and South Africa have been added. 26/09/2016: Publication reference added.