Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

A Randomized Double Blind Placebo Controlled Trial of Rifapentine and Isoniazid for Prevention of Tuberculosis in People With Diabetes

Sponsors

Lead Sponsor: Dr. Nyanda Elias Ntinginya

Collaborator: Stichting Katholieke Universiteit- Radboudumc (RUMC), Netherlands
Otago University, New Zealand
Makerere University
St George's, University of London, United Kingdom
Kilimanjaro Christian Medical University College (KCMUCo), Tanzania
Uganda Martyrs Hospital Lubaga, Uganda
King's College London

Source National Institute for Medical Research, Tanzania
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.

Overall Status Not yet recruiting
Start Date January 2021
Completion Date May 2024
Primary Completion Date May 2024
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
First diagnosis of TB Through study completion, median of 33 months follow-up
Secondary Outcome
Measure Time Frame
Occurrence of possible, probable or definite TB disease At least 24 months post randomisation
Occurrence of an adverse event From randomisation to 60 days after end of study treatment
Treatment completion Defined as > 11 of 12 doses of treatment over no more than 16 weeks.
All-cause mortality At least 24 months post randomisation
Occurrence of possible, probable, or definite TB, or death At least 24 months post randomisation
Enrollment 3000
Condition
Intervention

Intervention Type: Drug

Intervention Name: Isoniazid and Rifapentine (INH-RPT)

Description: Oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.

Arm Group Label: Isoniazid and Rifapentine (INH-RPT)

Other Name: 3HP

Intervention Type: Drug

Intervention Name: Placebo

Description: Participants in the control group will receive placebo once weekly for 12 weeks

Arm Group Label: Control

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Issa Sabi, MD.

Phone: +255 25 250 3364

Email: [email protected]

Verification Date

October 2020

Responsible Party

Type: Sponsor-Investigator

Investigator Affiliation: National Institute for Medical Research, Tanzania

Investigator Full Name: Dr. Nyanda Elias Ntinginya

Investigator Title: Director, NIMR - Mbeya Medical Research Centre

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Isoniazid and Rifapentine (INH-RPT)

Type: Experimental

Description: Participants in intervention arm will receive an oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.

Label: Control

Type: Placebo Comparator

Description: Participants in the control arm will receive placebo once weekly for 12 weeks.

Acronym PROTID
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov