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Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus (PROTID)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04600167
Recruitment Status : Not yet recruiting
First Posted : October 23, 2020
Last Update Posted : October 23, 2020
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
Dr. Nyanda Elias Ntinginya, 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.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Tuberculosis Drug: Isoniazid and Rifapentine (INH-RPT) Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized Double Blind Placebo Controlled Trial of Rifapentine and Isoniazid for Prevention of Tuberculosis in People With Diabetes
Estimated Study Start Date : January 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis

Arm Intervention/treatment
Experimental: 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.
Drug: Isoniazid and Rifapentine (INH-RPT)
Oral combination of rifapentine (RPT, 900 mg) and isoniazid (INH, 900 mg), once-weekly for 12 weeks.
Other Name: 3HP

Placebo Comparator: Control
Participants in the control arm will receive placebo once weekly for 12 weeks.
Drug: Placebo
Participants in the control group will receive placebo once weekly for 12 weeks




Primary Outcome Measures :
  1. First diagnosis of TB [ Time Frame: 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 :
  1. Occurrence of possible, probable or definite TB disease [ Time Frame: At least 24 months post randomisation ]
  2. Occurrence of an adverse event [ Time Frame: From randomisation to 60 days after end of study treatment ]
  3. Treatment completion [ Time Frame: Defined as > 11 of 12 doses of treatment over no more than 16 weeks. ]
  4. All-cause mortality [ Time Frame: At least 24 months post randomisation ]
  5. Occurrence of possible, probable, or definite TB, or death [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04600167


Contacts
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Contact: Issa Sabi, MD. +255 25 250 3364 isabi@nimr-mmrc.org
Contact: Nyanda E Ntinginya, MD., MSc., PhD. +255 25 250 3364 nelias@nimr-mmrc.org

Sponsors and Collaborators
Dr. Nyanda Elias Ntinginya
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
Investigators
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Study Chair: Nyanda E Ntinginya, MD, MSc., Ph.D Mbeya Medical Research Center, National Institute for Medical Research, Tanzania
Principal Investigator: 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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Dr. Nyanda Elias Ntinginya, Director, NIMR - Mbeya Medical Research Centre, National Institute for Medical Research, Tanzania
ClinicalTrials.gov Identifier: NCT04600167    
Other Study ID Numbers: NIMR-MB-002
First Posted: October 23, 2020    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Nyanda Elias Ntinginya, National Institute for Medical Research, Tanzania:
Tuberculosis
Drugs
Social science
Health systems
Epidemiology
Diabetes
Additional relevant MeSH terms:
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Tuberculosis
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Infections
Isoniazid
Rifapentine
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Antibiotics, Antitubercular
Leprostatic Agents