GXT - GeneXpert or Chest-X-ray or Tuberculin Skin Testing for Household Contact Assessment: a Cluster Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 1,589
- 试验地点
- 4
- 主要终点
- proportion starting therapy within 3 months of the index TB patient starting active TB treatment
研究概览
简要总结
The objective of the study is to compare outcomes from three different strategies for the management of household (HH) contacts of individuals with newly diagnosed microbiologically confirmed active pulmonary TB. The study is a cluster randomized trial with three arms of equal size. The first eligible member of the HH who provides signed informed consent to participate will be randomized to one of the three strategies. The three different study arms are as follows:
- Standard care (control arm): Participants will receive symptom screening and tuberculin skin testing (TST). If symptom screen positive and/or TST positive, they undergo chest x-rays (CXR). If CXR abnormal, they undergo microbiological investigation. If CXR normal or if microbiological investigation negative, TST positive receive latent TB infection (LTBI) treatment. If microbiological investigation is positive, they will be offered treatment for active TB. For children under 5 years of age in Brazil, sputum induction will be performed for bacteriological investigation
- GeneXpert (GX): Participants follow an algorithm similar to the standard care, however participants with positive symptom screen and/or positive TST will receive GX (i.e., GX replaces CXR in standard care algorithm). GX positive are considered to have active TB. TST positive and GX negative receive LTBI treatment. If an individual is not able to provide sputum, they will undergo a CXR.
- CXR for all/NoTST: Participants will receive symptom screening and CXR. No TST will be performed. If CXR abnormal or symptom positive, they undergo microbiological investigation. If the CXR is normal, and/or microbiological investigations negative - they receive LTBI treatment as per national guidelines. If microbiological investigation is positive they will be offered treatment for active TB.
The study population includes HIV uninfected persons aged 5-50 years who are HH contacts of individuals with newly diagnosed microbiologically confirmed active pulmonary TB. The planned number of household contacts to recruit is about 1434 in total, or about 455 for each of the three arms. The study will take place in Benin and Brazil.
The primary study outcome is, of those eligible for LTBI therapy, the proportion starting therapy within 3 months of the index TB patient starting active TB treatment. Secondary outcomes measured in each study arm include societal costs, prevalence of microbiologically confirmed and clinically diagnosed active TB, prevalence of TB infection, Incidence of adverse events, proportion who complete LTBI therapy, sensitivity and specificity of Chest Xray reading in each study side, and prevalence of active TB diagnosed using CXR in participants who cannot produce a sputum sample. Details of the statistical analysis plan for each primary and secondary outcome are provided below. Applicable for Brazil only: To evaluate the applicability and performance of material for bacteriological investigation obtained from induced sputum in children under 5 years of age.
Study participants will be recruited over 18 months. Participants will be followed until LTBI treatment is completed.
详细描述
Background:
At a recent United Nations high level conference on TB a target was set that more than 30 million individuals should be treated for LTBI over the next 5 years. This ambitious goal will require massive scaling up of LTBI diagnosis and treatment - which will be challenging, if not impossible, with current approaches to diagnosis and treatment of latent TB. Two aspects of management of LTBI - need for CXR and need for TST - are controversial, as both can create important barriers to LTBI initiation, thereby reducing the individual as well as public health benefits of treatment. For TST, difficulties in training and quality assurance of administration and reading, and a global shortage of tuberculin material have reduced uptake. CXR was recommended by WHO in its 2018 guidelines for LTBI management as part of investigations to rule our active TB, however CXR services are not accessible in many settings and even if accessible, the cost for a CXR often falls on patients and is often prohibitively expensive. An alternate strategy is to use GeneXpert equipment, with the Xpert MTB/Rif test (hereafter labelled GX) to replace CXR to exclude prevalent active TB.
Study Objectives:
To compare outcomes from three different strategies for the management of HIV uninfected persons aged 5-50 years who are HH contacts of newly diagnosed microbiologically confirmed active pulmonary TB. (0-5 years only in Brazil)
Design:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Index TB patients:
- •New diagnosis of pulmonary microbiologically confirmed (smear, GX or culture) active TB within 30 days of treatment initiation.
- •For Brazil: a new diagnosis of clinically pulmonary active is eligible.
- •Must have at least one identified household contact, and HHC investigation has not been started already.
- •Must agree to allow research team to access their medical history and approach their household contacts.
- •Household contacts:
- •Age 5-50 years for Benin and Age 0-50 for Brazil
- •On average in the past 3 months - slept in the same house, at least one night per week, or spent at least one hour per day for 5 days per week.
- •Pregnant woman can be included.
- •People with prior active TB or latent TB therapy will be included. These participants will be assessed for prevalent active TB, although they will not be treated for LTBI. Hence they will be included in the analyses of yield of active case finding, but excluded from analyses of numbers diagnosed and treated for LTBI.
排除标准
- •Index TB patients:
- •Known drug-resistant TB (INH resistant, multidrug resistance or rifampin resistance) may be excluded - after discussion in each country with TB program officials. If the TB programme's policy is to screen contacts of MDR cases for active TB only and not provide any LTBI therapy, then index TB patients with MDR will be excluded as well as their HHCs. However, if the national TB program policy is to treat such individuals with standard LTBI therapy (since some HHCs of MDR patients will develop TB with drug-sensitive isolates later), then these index TB patients and their HHCs will be eligible. Hence, this will be a country-specific exclusion criterion.
- •Index TB patient with previous history of active TB (because their HHC may have undergone investigation before - which may change their need for study interventions, and also potentially change their perceptions and behaviours in the study).
- •Only has extra-pulmonary TB.
- •No identified household contacts.
- •Household contacts:
- •Members of the household, but do not meet the minimum time definitions for HH contacts.
- •Had TST/IGRA within 3 months.
- •Had a CXR on the same day or after the date of diagnosis of the index TB patient.
- •People living with HIV. (In most TB programs, HH contacts have unknown HIV status; HIV testing is recommended by WHO only if the index TB patient is known to have HIV co-infection). Contacts will be asked if they have been previously diagnosed to have HIV infection, and also asked if they are taking anti-retroviral therapy (if patients are receiving any medications, these will be checked carefully to verify what these are, and in particular if they are on anti-retroviral therapy). Both questions will be asked because some patients may be on therapy, but are not aware of the indication, or they may not wish to divulge their HIV status. If HHC are on anti-retroviral therapy and/or provide a history of previous HIV diagnosis, then they will be excluded, because the WHO recommended algorithm for investigation of household contacts who are HIV infected is different from that followed in the study arms. All index TB patients should undergo HIV testing based on national algorithm. If the index TB patient is found to be HIV positive, partner notification services will be recommended to the person living with HIV. The children of women who are HIV-infected should also undergo HIV testing. HIV testing will be offered to all household contacts who have not been HIV-tested within the last 6 months. If any household contact is found to be HIV-infected, they will be excluded pre-randomization. If there is a significant delay between identification of the household contacts and obtaining the HIV result, the HHCs can be randomized and then excluded post-randomization. These HHCs will be excluded from the modified intention to treat analysis, which will be the primary analysis. All HHCs identified to have HIV-infection will undergo investigations and treatment following WHO guidelines for HIV-infected household contacts.
- •If one member family refuses to participate to the study and has no objection to have the other HH members to participate in the study, then we can proceed with the consent process with the other HHC. But if one household contact refuses to participate and objects to other HH members to take part of the study, then none of the HHC in this family can participate in the study. It is not necessary that all of the HHC signed consent but simply that no one objects. At any time a participant can refuse any test, or have other investigations - as ordered by their doctor/nurse or if they prefer).
结局指标
主要结局
proportion starting therapy within 3 months of the index TB patient starting active TB treatment
时间窗: LTBI treatment initiation within 3 months of the index TB patient starting active TB treatment.
Of those eligible (measured or estimated) for LTBI therapy, the proportion starting therapy within 3 months of the index TB patient starting active TB treatment.
次要结局
- Societal costs (health system and patient costs) of the full cascade of care(from the time of randomization until the end of investigations or the end of the second month of TB related treatment)
- Incidence of grade 1-4 adverse events related to LTBI therapy.(from treatment initiation until the end of treatment case report form (CRF) has been completed)
- Sensitivity and specificity of CXR(at baseline)
- Proportion of participants who complete LTBI therapy(Approximately 4 to 6 months after treatment initiation (depending on regimen used))
- Prevalence of microbiologically confirmed and clinically diagnosed active TB(at baseline)
- Prevalence of active TB diagnosed using CXR in participants who cannot produce a sputum sample.(at baseline)
- The outcome measure of performance is the percentage of patients with valid specimens obtained by the induction of sputum over all patients with indication for this technique.(at baseline)
- Prevalence of positive TST (>5 mm or >10 mm)(at baseline)
研究者
Dick Menzies
Senior investigator at Research Institute of Mcgill Unniversity Health Centre
McGill University Health Centre/Research Institute of the McGill University Health Centre