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
- 2
- 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
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)