A Pragmatic Randomised Study to Optimise Screening, Prevention and Care for Tuberculosis in Malawi
PROSPECT
1 other identifier
interventional
1,455
1 country
1
Brief Summary
A pragmatic open, three-arm individually-randomised controlled trial and economic evaluation will be conducted in one primary health care centre in Blantyre, Malawi, where HIV and TB are major contributors to early mortality. Participants will be adults with symptoms of tuberculosis (cough of any duration) attending the primary clinic with an acute care episode. We will exclude adults who have taken treatment for TB within the previous 6-months, who are taking isoniazid preventive therapy, who are not resident of Blantyre, or who plan to move out of Blantyre in the following 6-months. Participants will be randomly allocated into one of three groups: Group 1: Standard of care: Participants will be seen by facility health workers and receive clinician-directed screening for HIV and TB according to Malawi national guidelines. Group 2: Optimised HIV testing and treatment linkage: Participants will be offered testing for HIV using rapid oral fluid kits by research assistants. Those with confirmed HIV infection will be linked to the HIV care clinic where facility healthworkers will screen for TB using standard sputum-based diagnostics. Group 3: Optimised TB diagnosis, HIV screening and treatment linkage: Participants will receive a high-throughput and high-sensitivity TB screening intervention, in addition to the HIV testing intervention. This will comprise of an initial digital chest x-ray classified by the CAD4TB image-recognition software as either "high probability of TB", or "low probability of TB". Participants whose x-rays are suggestive of TB will receive confirmatory sputum testing with Xpert MTB/Rif Ultra cartridges, whilst participants whose x-rays have a low probability of TB will be referred to facility healthworkers for routine care. All participants will be seen at the health facility at day 56, where they will be tested for HIV (if not on ART) and screened for TB. The Primary Trial Outcome will compare between groups the time to tuberculosis treatment initiation by day 56. The trial is sufficiently powered to permit 3 pairwise comparisons between groups (i.e. Group 1 vs. 2; Group 2 vs. 3; and Group 1 vs. 3). This three-arm pragmatic trial design allows us to efficiently answer two separate, important public health questions: firstly, by comparing Group 2 to Group 1, we should be able to determine whether HIV care should be prioritised for adults with TB symptoms. Additionally, by comparing Group 3 to Group 2, we will provide strong evidence for the effectiveness of an optimised and integrated HIV and TB diagnostic and treatment linkage approach.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Nov 2018
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 26, 2018
CompletedFirst Posted
Study publicly available on registry
May 9, 2018
CompletedStudy Start
First participant enrolled
November 15, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2020
CompletedDecember 10, 2019
December 1, 2019
1 year
April 26, 2018
December 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to tuberculosis treatment initiation
The primary trial outcome will be time in days - from Day 0 up to but not including Day 56 - to tuberculosis treatment initiation, evaluated at Day 56 following randomization. Analysis of the primary outcome will be done on an intention to treat basis, with all participants analysed according to the group to which they were randomised. Time to TB treatment outcome analysis will be right censored at Day 56 from randomisation if TB treatment is not initiated, or at day of loss to follow-up. We will make three pair-wise comparisons (Group 2 vs. Group 1; Group 3 vs. Group 2; and Group 3 vs. Group 1).
Measured at 56 days after randomisation
Secondary Outcomes (9)
Same day TB treatment initiation
Measured at 56 days after randomisation
Undiagnosed/untreated microbiologically-confirmed pulmonary tuberculosis
Measured at 56 days after randomisation
Undiagnosed/untreated HIV
Measured at 56 days after randomisation
Time to antiretroviral therapy initiation
Measured at 56 days after randomisation
Mortality
Measured at 56 days after randomisation
- +4 more secondary outcomes
Other Outcomes (2)
Sex-and microbiological TB status-stratified analysis
Measured at 56 days after randomisation
Exploratory Bayesian analysis
Measured at 56 days after randomisation
Study Arms (3)
Group 1 (Standard of care)
NO INTERVENTIONParticipants will be directed to the clinic waiting area to be seen by facility health workers who will direct all further care without any further input from the study team. Available to facility health workers will be: * Routine HIV testing and counselling, provided by Facility HIV Testers using a rapid fingerprick kit-based algorithm. * Routine TB screening, with both sputum smear microscopy and Xpert MTB/Rif testing available onsite. * Routine linkage to the onsite HIV clinic, where patients are registered and assessed for initiation onto antiretroviral therapy by facility HIV Care Clinic health workers. Malawi guidelines recommend universal treatment for HIV. HIV Care Clinic health workers will additionally have access to TB screening tests as described above. * Routine linkage to the onsite TB clinic, where patients are registered and initiated onto anti-TB treatment. Malawi guidelines recommend universal HIV testing for all patients with confirmed TB.
Group 2 (Optimised HIV screening and linkage to care)
ACTIVE COMPARATORParticipants will be directed to the study room located in a separate building. After identity validation participants will be offered a supervised HIV self-testing intervention. Participants will be given brief pre-test instructions and will be asked to self-test in a private area using the OraQuick 1/2 (OraSure Technologies) oral fluid HIV kit. Participants will be supported to read their HIV test result by study Research Assistants, and provided with confirmatory HIV testing by the trained Research Assistants. * HIV-positive participants will be supported by Research Assistants to register at the onsite HIV care clinic, and all further care (including TB screening) will be directed by facility health workers without any further study input. * HIV-negative participants will be referred to the clinic waiting area (with a copy of their HIV test results) to be seen by the facility health workers who will direct all further investigations without further study input.
Group 3 (Optimised HIV and TB screening and linkage to care)
ACTIVE COMPARATORParticipants will be directed to the Study Room. After identity validation, they will be offered the HIV self-testing and linkage intervention as described above for Group 2. Additionally, they will be offered a TB screening intervention comprising of: * A digital chest x-ray using the study MinXray unit. * Chest x-rays will be immediately classified by the CAD4TB software running on the MinXray unit laptop as either "high probability of TB", or "low probability of TB". * Participants whose chest x-rays have a low probability of TB will be referred to facility health workers (at either the onsite HIV care clinic if HIV-positive, or the clinic waiting area), with copies of their results for further routine care, and without further study input. * Participants whose chest x-ray x-ray show a high probability of TB will submit a single spot sputum sample for Xpert testing (done in the clinic). Those with confirmed TB will be linked to register at the onsite TB clinic.
Interventions
As described in group descriptions
As described in group descriptions
Eligibility Criteria
You may qualify if:
- Attends Study Clinic with an acute care episode
- years of age or older on the day of clinic attendance
- Has symptoms of tuberculosis (cough of any duration)
- Is resident within urban Blantyre
- Provides informed consent to participate
You may not qualify if:
- Taking treatment for tuberculosis on the day of clinic attendance
- Has taken any treatment for tuberculosis in the 6-months prior to clinic attendance
- Is taking isoniazid preventive therapy
- Plans to move out of Blantyre to live elsewhere in the following 6-months
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Liverpool School of Tropical Medicinelead
- Malawi-Liverpool-Wellcome Trust Clinical Research Programmecollaborator
- London School of Hygiene and Tropical Medicinecollaborator
- University of Liverpoolcollaborator
- McGill Universitycollaborator
- Kamuzu University of Health Sciencescollaborator
Study Sites (1)
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Blantyre, Chichiri, 3, Malawi
Related Publications (2)
MacPherson P, Webb EL, Kamchedzera W, Joekes E, Mjoli G, Lalloo DG, Divala TH, Choko AT, Burke RM, Maheswaran H, Pai M, Squire SB, Nliwasa M, Corbett EL. Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis. PLoS Med. 2021 Sep 9;18(9):e1003752. doi: 10.1371/journal.pmed.1003752. eCollection 2021 Sep.
PMID: 34499665DERIVEDMacPherson P, Webb EL, Lalloo DG, Nliwasa M, Maheswaran H, Joekes E, Phiri D, Squire B, Pai M, Corbett EL. Design and protocol for a pragmatic randomised study to optimise screening, prevention and care for tuberculosis and HIV in Malawi (PROSPECT Study). Wellcome Open Res. 2018 Nov 21;3:61. doi: 10.12688/wellcomeopenres.14598.3. eCollection 2018.
PMID: 30542662DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- HEALTH SERVICES RESEARCH
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 26, 2018
First Posted
May 9, 2018
Study Start
November 15, 2018
Primary Completion
December 1, 2019
Study Completion
June 1, 2020
Last Updated
December 10, 2019
Record last verified: 2019-12
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Within four months of trial completion
- Access Criteria
- Open access
We are strongly committed to ensuring that the trial datasets are made openly available, and that all code used in the analysis are published to allow fully reproducible research. The data collected by this research will be of importance to other researchers and the public, and could for example be used by other researchers conducting meta-analysis, or by policymakers modelling the potential return on investment of implementing interventions within their settings. Therefore, we will establish a public online GitHub repository, where the final anonymised individual participant trial dataset and code to allow reproduction of all analysis will be published.