A benefit-risk trial of 1-month rifapentine and isoniazid to prevent tuberculosis and reduce morbidity in people with non-communicable multimorbidity

一项为期 1 个月的利福喷汀和异烟肼预防结核病并降低非传染性多病患者发病率的效益风险试验

• 批准号: MR/Y004914/1
• 负责人: Molebogeng Rangaka
• 金额: $ 354.67万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY004914%2F1
• 关键词: benefit; risk; trial; month; rifapentine

TB causes the most deaths than any other infectious disease worldwide. People who live in poor countries are mostaffected; this is at a large personal and financial cost to the individuals, their families and communities. Disease can beprevented by giving TB drugs to people who are infected with the bacteria that causes TB, this is called TB preventivetreatment.The World Health Organization (WHO) currently recommends TB preventive treatment for people who are most at risk ofdeveloping TB such as people who live in the same house as a person with TB, and also for people living with HIV. Forthese individuals, it is acknowledged that TB preventive treatment will achieve more benefit than harm. People withdiabetes also have an increased chance of developing TB disease and dying from TB. However, WHO does not currentlyrecommend TB preventive treatment since it is not clear if the benefit would outweigh the risks of treatment. There is notenough evidence to inform this decision especially since the only option on offer is the standard TB prevention treatmentwith 6 or 9 months of isoniazid which is taken daily and can cause harm especially to the liver. Moreover, benefit may belimited since providing good WHO standard care for diabetes could already reduce the risk of TB in the future. The aim ofWHO standard care for diabetes is to control blood sugar levels and by so doing, research suggests the risk of developingTB would also be reduced. In addition, standard care for diabetes includes a medicine called metformin which has beenrecently shown to reduce the risk of developing TB in people prescribed this medicine compared to those not prescribedthe medicine.The new short-duration treatment with one month of the TB drugs rifapentine and isoniazid (1HP) was shown to prevent TBdisease in people infected with HIV. Moreover, 1HP has other benefits since more people complete the short treatment,and it causes fewer side effects. We think this new treatment may alter the balance of benefit against the harms. Thiswould result in a change in WHO policy in favour of providing TB preventive treatment to people living with diabetes. Thetreatment has not not been studied in people with diabetes or people without HIV. We plan to find the best strategy for TBprevention for people with diabetes who are HIV-uninfected and likely infected with TB (as shown by a test of exposure toTB). A positive test would indicate an increased risk to develop TB in the future. We will carry out a study that will placepeople in a random manner, like tossing a coin, to a group that receives the standard care for diabetes with 1HP or a groupthat receives diabetes care alone. That type of study is called a randomised controlled study. In this study, we will assesswho gets TB disease and who develops side effects from the treatments in each group. If 1HP reduces the chance ofdeveloping TB and does so without substantial side-effects, we think WHO policy will change quickly to recommendprevention of TB in people with diabetes. However, if giving 1HP in addition to standard care for diabetes is not better thanstandard care alone, the current recommendation would not change thus avoid unnecessary harm from TB drugs. Our trialwill recruit 4,130 male and female individuals aged 15 years and older with diabetes, and who reside in Philippines andSouth Africa. The project will run for 5 years.

结核病是世界上死亡人数最多的传染病。生活在贫穷国家的人们受到的影响最大;这给个人、家庭和社区带来了巨大的个人和经济代价。结核病可以通过给感染结核病细菌的人服用结核病药物来预防，这被称为结核病预防性治疗。世界卫生组织（WHO）目前建议对那些最有可能患结核病的人进行结核病预防性治疗，例如与结核病患者住在同一个房子里的人，以及艾滋病毒感染者。对于这些人来说，结核病预防性治疗的利大于弊是公认的。糖尿病患者患结核病和死于结核病的机会也增加了。然而，世卫组织目前并不推荐结核病预防性治疗，因为尚不清楚治疗的益处是否大于风险。没有足够的证据支持这一决定，特别是因为唯一的选择是标准的结核病预防治疗，每天服用6或9个月的异烟肼，可能会对肝脏造成损害。此外，受益可能有限，因为为糖尿病提供良好的世卫组织标准护理已经可以降低未来结核病的风险。世卫组织糖尿病标准治疗的目的是控制血糖水平，研究表明，通过这样做，患结核病的风险也会降低。此外，糖尿病的标准治疗包括一种名为二甲双胍的药物，最近的研究表明，与未开这种药的人相比，开这种药的人患结核病的风险降低。新的结核病药物利福喷丁和异烟肼（1HP）一个月的短期治疗被证明可以预防艾滋病毒感染者患结核病。此外，1HP还有其他好处，因为更多的人完成了短期治疗，而且副作用更少。我们认为这种新疗法可能会改变利与弊的平衡。这将导致世卫组织的政策发生变化，有利于向糖尿病患者提供结核病预防性治疗。该疗法尚未在糖尿病患者或未感染艾滋病病毒的人中进行研究。我们计划为未感染艾滋病毒但可能感染结核病的糖尿病患者（如结核病暴露试验所示）找到预防结核病的最佳策略。阳性测试将表明未来患结核病的风险增加。我们将进行一项研究，将人们以随机的方式，像抛硬币一样，分为接受标准治疗的糖尿病组和接受单独治疗的糖尿病组。这种类型的研究被称为随机对照研究。在这项研究中，我们将评估每个组中谁会患上结核病，谁会因治疗而产生副作用。如果1HP降低了患结核病的机会，并且没有明显的副作用，我们认为世卫组织的政策将迅速改变，以预防糖尿病患者的结核病。然而，如果在糖尿病标准治疗的基础上给予1HP并不比单独的标准治疗更好，那么目前的建议将不会改变，从而避免结核病药物造成不必要的伤害。我们的试验将招募4,130名年龄在15岁及以上的糖尿病患者，他们居住在菲律宾和南非。该项目将运行5年。