Clinical trial NCT04600167: Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus
Official title: A Randomized Double Blind Placebo Controlled Trial of Rifapentine and Isoniazid for Prevention of Tuberculosis in People With Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Diabetes Mellitus
Tuberculosis
Keywords: Tuberculosis
Drugs
Social science
Health systems
Epidemiology
Diabetes
Lead sponsor: National Institute for Medical Research, Tanzania
Sponsor class: OTHER_GOV
Collaborators: name: Stichting Katholieke Universiteit- Radboudumc (RUMC), Netherlands
name: Otago University, New Zealand
name: Makerere University
name: St George's, University of London, United Kingdom
name: Kilimanjaro Christian Medical University College (KCMUCo), Tanzania
name: Uganda Martyrs Hospital Lubaga, Uganda
name: King's College London
First posted: 2020-10-23
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Diabetes mellitus (DM) increases susceptibility to Tuberculosis (TB) and worsens TB patient outcomes. The number of patients with combined TB and DM now outnumbers that of combined TB and HIV and it has been estimated that 15-30% of TB disease may be attributable to diabetes globally. This may be expected to rise substantially as DM prevalence increases. Treatment of Latent TB Infection (LTBI) in this population will likely have a significant clinical benefit. Similar to HIV-infected individuals, those with DM might benefit from therapy to prevent the development of TB disease. Current international guidelines do not recommend LTBI management in people with DM, but this is because no studies have examined the risk-benefit ratio of such an intervention. To date, no RCTs have been conducted to investigate the efficacy and safety of preventive treatment of LTBI in DM patients. Based on evidence on effectiveness, safety, and treatment completion rates, 3HP has been selected as the regimen of choice for this study of African people living with DM. People living with DM will be randomized to 3HP or placebo to determine the efficacy of 3HP in the prevention of TB disease in this population. PROTID's preventive treatment of LTBI among people with DM will generate the first solid evidence to support or refute the use of preventive treatment against TB in people with DM.


Eligibility criteria: Inclusion Criteria:

1. Enrolled in diabetes care with a history of DM and current use of anti-diabetic medication ('known DM'); OR in the absence of anti-diabetic medication an HbA1c of =6.5% (48 mmol/mol) or a fasting venous plasma glucose of =7.0 mmol (126 mg/dl). For those with no previously known DM a repeat test above the diagnostic cut-point is required to confirm the diagnosis ('new DM')
2. Adult (18 years or older)
3. Diagnosed with LTBI, defined as a positive IGRA test or TST reactivity =10 mm
4. Voluntarily signed Informed Consent Form
5. If sexually active, willing to use an effective contraceptive method for the duration of preventive therapy.

Exclusion Criteria:

1. Weight \<45 kg
2. Previous TB disease, defined as either bacteriologically confirmed or clinically diagnosed and treated
3. Treatment with a rifamycin medication or isoniazid in the previous 2 years.
4. Diagnosis of probable or definite TB during screening
5. Confirmed HIV-infection or receiving antiretroviral treatment
6. Liver dysfunction, defined as serum aspartate aminotransferase (AST) level 5 times the upper limit of normal
7. Pregnant or planning to become pregnant in the next 3 months, or lactating
8. Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
9. Other conditions inapplicable for participation in this study, such as likely to fail to adhere to study commitment or to complete the whole study, at the discretion of the site investigator

Primary outcomes:
measure: First diagnosis of TB
timeFrame: Through study completion, median of 33 months follow-up
Secondary outcomes:
measure: Occurrence of possible, probable or definite TB disease
timeFrame: At least 24 months post randomisation
measure: Occurrence of an adverse event
timeFrame: From randomisation to 60 days after end of study treatment
measure: Treatment completion
timeFrame: Defined as > 11 of 12 doses of treatment over no more than 16 weeks.
measure: All-cause mortality
timeFrame: At least 24 months post randomisation
measure: Occurrence of possible, probable, or definite TB, or death
timeFrame: At least 24 months post randomisation
Other outcomes:
Locations:
city: Mbeya
country: Tanzania
facility: Mbeya zonal referral hospital
city: Moshi
country: Tanzania
facility: Kilimanjaro Christian Medical Center
city: Kampala
country: Uganda
facility: Makerere University
city: Kampala
country: Uganda
facility: Martyrs Hospital Lubaga
Study officials:
affiliation: Mbeya Medical Research Center, National Institute for Medical Research, Tanzania
name: Nyanda E Ntinginya, MD, MSc., Ph.D
role: STUDY_CHAIR
affiliation: Kilimanjaro Christian Medical Centre,Moshi,Tanzania
name: Nyasatu Chamba, MD.
role: PRINCIPAL_INVESTIGATOR
affiliation: Makerere University, Makerere, Uganda
name: Irene Andia- Biraro, MD., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Martyrs Hospital Lubaga, Makerere, Uganda
name: Davis Kibirige, MD, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ntinginya NE, Te Brake L, Sabi I, Chamba N, Kilonzo K, Laizer S, Andia-Biraro I, Kibirige D, Kyazze AP, Ninsiima S, Critchley JA, Romeo R, van de Maat J, Olomi W, Mrema L, Magombola D, Mwayula IH, Sharples K, Hill PC, van Crevel R; PROTID Consortium. Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial. Trials. 2022 Jun 10;23(1):480. doi: 10.1186/s13063-022-06296-8.
citation: Olomi W, Andia Biraro I, Kilonzo K, Te Brake L, Kibirige D, Chamba N, Elias Ntinginya N, Sabi I, Critchley J, Sharples K, Hill PC, Van Crevel R. Tuberculosis Preventive Therapy for People With Diabetes Mellitus. Clin Infect Dis. 2022 Apr 28;74(8):1506-1507. doi: 10.1093/cid/ciab755. No abstract available.