Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

Diabetes Mellitus Clinical Trial

— PROTID  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04600167
• Other study ID #: NIMR-MB-002
• Status: Recruiting
• Phase: Phase 3
• Start date: June 17, 2022
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: National Institute for Medical Research, Tanzania
• Contact: Issa Sabi, MD, MMed, PhD
• Phone: +255 25 250 3364
• Email: isabi[@]nimr-mmrc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3000
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Tuberculosis

Intervention

Drug:
• Isoniazid and Rifapentine (INH-RPT)
Oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.
• Placebo
Participants in the control group will receive placebo once weekly for 12 weeks

Locations

Country	Name	City	State
Tanzania	Mbeya zonal referral hospital	Mbeya
Tanzania	Kilimanjaro Christian Medical Center	Moshi
Uganda	Makerere University	Kampala
Uganda	Martyrs Hospital Lubaga	Kampala

Sponsors (8)

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

Countries where clinical trial is conducted

Tanzania,  Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First diagnosis of TB	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.	Through study completion, median of 33 months follow-up
Secondary	Occurrence of possible, probable or definite TB disease		At least 24 months post randomisation
Secondary	Occurrence of an adverse event		From randomisation to 60 days after end of study treatment
Secondary	Treatment completion		Defined as > 11 of 12 doses of treatment over no more than 16 weeks.
Secondary	All-cause mortality		At least 24 months post randomisation
Secondary	Occurrence of possible, probable, or definite TB, or death	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.	At least 24 months post randomisation