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

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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.