Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

NCT ID: NCT04600167

Last Updated: 2023-03-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 3000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-17
• Study Completion Date: 2025-12-31

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.

Conditions

Diabetes Mellitus; Tuberculosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Isoniazid and Rifapentine (INH-RPT)

Intervention Type: DRUG

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

Control

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

Isoniazid and Rifapentine (INH-RPT)

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Other Intervention Names

3HP

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Stichting Katholieke Universiteit- Radboudumc (RUMC), Netherlands

UNKNOWN

Sponsor Role: collaborator

Otago University, New Zealand

UNKNOWN

Sponsor Role: collaborator

Makerere University

OTHER

Sponsor Role: collaborator

St George's, University of London, United Kingdom

UNKNOWN

Sponsor Role: collaborator

Kilimanjaro Christian Medical University College (KCMUCo), Tanzania

UNKNOWN

Sponsor Role: collaborator

Uganda Martyrs Hospital Lubaga, Uganda

UNKNOWN

Sponsor Role: collaborator

King's College London

OTHER

Sponsor Role: collaborator

Dr. Nyanda Elias Ntinginya

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr. Nyanda Elias Ntinginya

Director, NIMR - Mbeya Medical Research Centre

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nyanda E Ntinginya, MD, MSc., Ph.D

Role: STUDY_CHAIR

Mbeya Medical Research Center, National Institute for Medical Research, Tanzania

Nyasatu Chamba, MD.

Role: PRINCIPAL_INVESTIGATOR

Kilimanjaro Christian Medical Centre,Moshi,Tanzania

Irene Andia- Biraro, MD., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Makerere University, Makerere, Uganda

Davis Kibirige, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Martyrs Hospital Lubaga, Makerere, Uganda

Locations

Mbeya zonal referral hospital

Mbeya, , Tanzania

Site Status: RECRUITING

Kilimanjaro Christian Medical Center

Moshi, , Tanzania

Site Status: RECRUITING

Makerere University

Kampala, , Uganda

Site Status: RECRUITING

Martyrs Hospital Lubaga

Kampala, , Uganda

Site Status: RECRUITING

Countries

Tanzania; Uganda

Central Contacts

Issa Sabi, MD, MMed, PhD

Role: CONTACT

isabi@nimr-mmrc.org

+255 25 250 3364

Nyanda E Ntinginya, MD., MSc., PhD.

Role: CONTACT

nelias@nimr-mmrc.org

+255 25 250 3364

Facility Contacts

Nyanda E Ntinginya, MD, MSc, PhD

Role: primary

nelias@nimr-mmrc.org

Issa Sabi, MD, MMed, PhD

Role: backup

isabi@nimr-mmrc.org

Nyasatu Chamba, MD, MMed

Role: primary

nyasatuchamba@yahoo.com

Kajiru Kilonzo, MD, MMed

Role: backup

k.kilonzo@kcri.ac.tz

Irene Andia- Biraro, MD, MMed, PhD

Role: primary

andiaodanga@yahoo.com

Davis Kibirige, MD, MMed, PhD

Role: primary

kibirigedavis@gmail.com

References

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.

Reference Type: DERIVED

PMID: 35689272 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34505132 (View on PubMed)

Other Identifiers

NIMR-MB-002

Identifier Type: -

Identifier Source: org_study_id