A Pragmatic Randomised Study to Optimise Screening, Prevention and Care for Tuberculosis in Malawi
试验速览
- 阶段
- 不适用
- 入组人数
- 1,455
- 试验地点
- 1
- 主要终点
- Time to tuberculosis treatment initiation
研究概览
简要总结
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.
详细描述
Ambitious global targets have been set to eliminate tuberculosis as a public health problem by 2035. However, in Africa, where HIV has driven extremely high incidence rates, progress in reducing new infections and TB deaths remains too slow.
We have previously demonstrated that adults seeking diagnosis and treatment for TB and HIV face considerable barriers, and have long delays in starting treatment with high pre-treatment mortality.
Efforts to reduce TB mortality have been hampered by limitations in TB diagnostics, with considerable uncertainty about how available and new tests can be best implemented.
The aim of the PROSPECT Study is therefore to investigate the effectiveness and cost-effectiveness of optimised TB/HIV diagnosis and treatment linkage interventions on TB and HIV case detection, treatment initiation and mortality.
Study design A pragmatic open, three-arm individually-randomised controlled trial and economic evaluation will be conducted in one primary health care centre in Blantyre, Malawi.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Attends Study Clinic with an acute care episode
- •18 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
排除标准
- •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
研究组 & 干预措施
Group 1 (Standard of care)
Participants 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)
Participants 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.
干预措施: Optimised HIV screening and linkage to care (Other)
Group 3 (Optimised HIV and TB screening and linkage to care)
Participants 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.
干预措施: Optimised HIV screening and linkage to care (Other)
Group 3 (Optimised HIV and TB screening and linkage to care)
Participants 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.
干预措施: Optimised tuberculosis screening and linkage to care (Other)
结局指标
主要结局
Time to tuberculosis treatment initiation
时间窗: Measured at 56 days after randomisation
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).
次要结局
- Quality of life (EQ5D visual analogue scale)(Measured at 56 days after randomisation)
- Cost-effectiveness(Measured at 56 days after randomisation)
- Mortality(Measured at 56 days after randomisation)
- TB treatment outcome(Measured at 6-months after randomisation)
- Time to antiretroviral therapy initiation(Measured at 56 days after randomisation)
- Same day TB treatment initiation(Measured at 56 days after randomisation)
- Quality of life (EQ5D utility score)(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)