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.

结核病是全世界造成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、他们的家庭和社区带来了巨大的个人和经济成本。可以通过给感染了引起结核病的细菌的人服用结核病药物来预防疾病，这称为结核病预防治疗。世界卫生组织（WHO）目前建议对最有可能患上结核病的人进行结核病预防治疗，例如与结核病患者以及艾滋病毒感染者住在同一所房子里。对于这些人来说，结核病预防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。然而，世卫组织目前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，即每天服用 6 或 9 个月的异烟肼，这种治疗尤其会对肝脏造成伤害。此外，获益可能有限，因为为糖尿病提供良好的世界卫生组织标准护理已经可以降低未来结核病的风险。世界卫生组织糖尿病标准护理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，糖尿病的标准护理包括一种名为二甲双胍的药物，最近显示，与未开这种药的人相比，开这种药的人患结核病的风险较低。新的短期治疗结核病药物利福喷汀和一个月异烟肼 (1HP) 被证明可以预防 HIV 感染者患结核病。此外，1HP 还有其他好处，因为更多的人完成短期治疗，并且副作用更少。我们认为这种新疗法可能会改变利弊之间的平衡。这将导致世卫组织政策发生变化，有利于向糖尿病患者提供结核病预防治疗。尚未对糖尿病患者或未感染艾滋病毒的人进行治疗研究。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找到预防结核病的最佳策略（如结核病暴露测试所示）。阳性检测表明未来患结核病的风险增加。我们将开展一项研究，以随机方式（如抛硬币）将人们分为接受 1HP 糖尿病标准护理的一组或单独接受糖尿病护理的一组。此类研究称为随机对照研究。在这项研究中，我们将评估每组中哪些人患有结核病以及哪些人因治疗而出现副作用。如果 1HP 降低了患结核病的机会，并且没有明显的副作用，我们认为世界卫生组织的政策将迅速改变，建议糖尿病患者预防结核病。然而，如果在糖尿病标准治疗的基础上给予 1HP 并不比单独标准治疗更好，则当前的建议不会改变，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 名居住在菲律宾和南非、年龄在 15 岁及以上、患有糖尿病的男性和女性患者。该项目将运行5年。