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

March 27, 2023 updated by: Dr. Nyanda Elias Ntinginya

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

3000

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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 Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Through study completion, median of 33 months follow-up

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of possible, probable or definite TB disease
Time Frame: At least 24 months post randomisation
At least 24 months post randomisation
Occurrence of an adverse event
Time Frame: From randomisation to 60 days after end of study treatment
From randomisation to 60 days after end of study treatment
Treatment completion
Time Frame: Defined as > 11 of 12 doses of treatment over no more than 16 weeks.
Defined as > 11 of 12 doses of treatment over no more than 16 weeks.
All-cause mortality
Time Frame: At least 24 months post randomisation
At least 24 months post randomisation
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.
At least 24 months post randomisation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dr. Nyanda Elias Ntinginya

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 17, 2022

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

September 15, 2020

First Submitted That Met QC Criteria

October 19, 2020

First Posted (Actual)

October 23, 2020

Study Record Updates

Last Update Posted (Actual)

March 29, 2023

Last Update Submitted That Met QC Criteria

March 27, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIMR-MB-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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