Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

NCT04600167 | Unknown Phase 3 DMC

• 1 other identifier: NIMR-MB-002
• Study Type: interventional
• Target: 3,000
• Locations: 2 countries
• Sites: 4

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

Keywords

Tuberculosis; Drugs; Social science; Health systems; Epidemiology; Diabetes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

Study Arms (2)

Isoniazid and Rifapentine (INH-RPT)

EXPERIMENTAL

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

Drug: Isoniazid and Rifapentine (INH-RPT)

Control

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Isoniazid and Rifapentine (INH-RPT) DRUG

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

Also known as: 3HP

Isoniazid and Rifapentine (INH-RPT)

Placebo DRUG

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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')
• Adult (18 years or older)
• Diagnosed with LTBI, defined as a positive IGRA test or TST reactivity =10 mm
• Voluntarily signed Informed Consent Form
• If sexually active, willing to use an effective contraceptive method for the duration of preventive therapy.

You may not qualify if:

• Weight \<45 kg
• Previous TB disease, defined as either bacteriologically confirmed or clinically diagnosed and treated
• Treatment with a rifamycin medication or isoniazid in the previous 2 years.
• Diagnosis of probable or definite TB during screening
• Confirmed HIV-infection or receiving antiretroviral treatment
• Liver dysfunction, defined as serum aspartate aminotransferase (AST) level 5 times the upper limit of normal
• Pregnant or planning to become pregnant in the next 3 months, or lactating
• Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation
• 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

Sponsors & Collaborators

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

Study Sites (4)

Mbeya zonal referral hospital

Mbeya, Tanzania

RECRUITING

Kilimanjaro Christian Medical Center

Moshi, Tanzania

RECRUITING

Makerere University

Kampala, Uganda

RECRUITING

Martyrs Hospital Lubaga

Kampala, Uganda

RECRUITING

Related Publications (2)

• 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.

  PMID: 35689272 DERIVED

• 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.

  PMID: 34505132 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Tuberculosis

Interventions

Isoniazid; rifapentine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Nyanda E Ntinginya, MD, MSc., Ph.D

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

  STUDY CHAIR

• Nyasatu Chamba, MD.

  Kilimanjaro Christian Medical Centre,Moshi,Tanzania

  PRINCIPAL INVESTIGATOR

• Irene Andia- Biraro, MD., Ph.D.

  Makerere University, Makerere, Uganda

  PRINCIPAL INVESTIGATOR

• Davis Kibirige, MD, Ph.D.

  Martyrs Hospital Lubaga, Makerere, Uganda

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Issa Sabi, MD, MMed, PhD

CONTACT

+255 25 250 3364; isabi@nimr-mmrc.org

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

CONTACT

+255 25 250 3364; nelias@nimr-mmrc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, NIMR - Mbeya Medical Research Centre

Study Record Dates

• First Submitted: September 15, 2020
• First Posted: October 23, 2020
• Study Start: June 17, 2022
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 29, 2023

Record last verified: 2023-03

Locations

TA (2); UG (2)