Project: Randomised Controlled Trial of Preventive Treatment of Latent Tuberculosis Infection in Patients with Diabetes Mellitus

Acronym	PROTID (Reference Number: RIA2018CO-2514)
Duration	01/01/2020 - 30/06/2024
Project Topic	An estimated one quarter of the world’s population have latent tuberculosis infection (LTBI), of whom 5- 10% will go on to develop TB disease at some stage. Screening and preventive treatment of LTBI is considered essential for global TB control. Children who have been in contact with a highly infectious tuberculosis (TB) case, and people with HIV have already been targeted for preventive treatment of LTBI. With short and effective treatment regimens available, the clear direction for global TB control is to expand preventive treatment to other high-risk groups. One such group is people with Diabetes Mellitus (DM) in TB-endemic countries. People with DM are an estimated 3.7 times more likely to develop TB than those without DM, and this risk is higher with poorly controlled DM. It is estimated that DM now accounts for >10% of TB globally, and this will increase significantly in the coming decades due to the dramatic rise in type 2 DM in TB endemic settings. DM not only increases someone’s risk of developing TB disease, but is also associated with more severe TB disease, TB treatment failure, recurrent TB disease and death. As such, screening and management of LTBI in people living with DM will likely yield substantial health gains and contribute to global TB control. We propose to perform the first randomized controlled trial (RCT) globally to evaluate the efficacy and potential impact of preventive treatment of LTBI in people living with DM. We will randomize 3000 people with DM and LTBI in Tanzania and Uganda to a 12-week course of rifapentine and isoniazid preventive therapy or placebo, with cumulative incidence of TB disease over 24-months follow-up as primary endpoint. 1000 people with DM but without evidence of LTBI will be followed in parallel to confirm whether their incidence of TB is too low to warrant preventive treatment. In addition, we will: (i) evaluate optimal ways to screen people with DM for LTBI and TB; (ii) address gaps in prevention and therapeutic management of combined TB and DM; and (iii) estimate the population impact and costeffectiveness of treatment of LTBI in people living with DM. Our project addresses an EDCTP prevention priority area (TB and comorbidity) and includes partners who have worked together previously (including an EC-funded consortium investigating TB-DM [TANDEM], for which the PI was scientific coordinator). The African centers have relevant RCT experience and high TB and DM burdens.
Network	EDCTP2
Call	Advances in product development for effective prevention, treatment and management of co-infections and co-morbidities

Project partner

Number	Name	Role	Country
1	Stichting Katholieke Universiteit- Radboudumc	Coordinator	Netherlands
2	King's College London	Partner	United Kingdom
3	Lubaga Hospital	Partner	Uganda
4	Makerere University	Partner	Uganda
5	National Institute for Medical Research - Tanzania	Partner	Tanzania
6	St George’s Hospital Medical School	Partner	United Kingdom
7	The Good Samaritan Foundation, Kilimanjaro Christian Medical Centre	Partner	Tanzania
8	University of Otago	Partner	New Zealand