Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

Phase 3

Recruiting

• Conditions: Diabetes Mellitus; Tuberculosis
• Interventions: Drug: Isoniazid and Rifapentine (INH-RPT); Drug: Placebo

• Registration Number: NCT04600167
• Lead Sponsor: Dr. Nyanda Elias Ntinginya

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-15
• Study First Submitted QC: 2020-10-19
• Study First Posted: 2020-10-23
• Study Start: 2022-06-17
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-27
• Last Update Posted: 2023-03-29
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3000

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isoniazid and Rifapentine (INH-RPT)	Isoniazid and Rifapentine (INH-RPT)	Participants in intervention arm will receive an oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.
Control	Placebo	Participants in the control arm will receive placebo once weekly for 12 weeks.

Primary Outcome Measures

Name	Time	Method
First diagnosis of TB	Through study completion, median of 33 months follow-up	The primary outcome will compare the rate of occurrence of TB disease (defined as definite or probable TB) in treatment and control groups. Definite TB disease will be confirmed by a culture or Xpert positive result for M. tuberculosis. Probable TB will be diagnosed according to an algorithm that takes into account symptoms, chest x-ray reading, sputum smear, histology and verbal autopsy results.

Secondary Outcome Measures

Name	Time	Method
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	Occurrence of possible, probable, or definite TB, or death, noting that a proportion of deaths are likely to be due to TB but not possible to confirm through verbal autopsy and clinical notes review.

Trial Locations

Locations (4)

Martyrs Hospital Lubaga; 🇺🇬 Kampala, Uganda

Makerere University; 🇺🇬 Kampala, Uganda

Mbeya zonal referral hospital; 🇹🇿 Mbeya, Tanzania

Kilimanjaro Christian Medical Center; 🇹🇿 Moshi, Tanzania