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

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