Back to results

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

Primary Purpose

Diabetes Mellitus, Tuberculosis

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Isoniazid and Rifapentine (INH-RPT)

Placebo

About this trial

This is an interventional prevention trial for Diabetes Mellitus focused on measuring Tuberculosis, Drugs, Social science, Health systems, Epidemiology, Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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

Sites / Locations

Mbeya zonal referral hospitalRecruiting
Kilimanjaro Christian Medical CenterRecruiting
Makerere UniversityRecruiting
Martyrs Hospital LubagaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Isoniazid and Rifapentine (INH-RPT)

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Occurrence of possible, probable or definite TB disease

Occurrence of an adverse event

Treatment completion

All-cause mortality

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.

Full Information

NCT ID

NCT04600167

First Posted

September 15, 2020

Last Updated

March 27, 2023

Sponsor

Dr. Nyanda Elias Ntinginya

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

1. Study Identification

Unique Protocol Identification Number

NCT04600167

Brief Title

Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

Acronym

PROTID

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 17, 2022 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Dr. Nyanda Elias Ntinginya

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetes Mellitus, Tuberculosis

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

3000 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Isoniazid and Rifapentine (INH-RPT)

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Isoniazid and Rifapentine (INH-RPT)

Other Intervention Name(s)

3HP

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

First diagnosis of TB

Description

Time Frame

Through study completion, median of 33 months follow-up

Secondary Outcome Measure Information:

Title

Occurrence of possible, probable or definite TB disease

Time Frame

At least 24 months post randomisation

Title

Occurrence of an adverse event

Time Frame

From randomisation to 60 days after end of study treatment

Title

Treatment completion

Time Frame

Defined as > 11 of 12 doses of treatment over no more than 16 weeks.

Title

All-cause mortality

Time Frame

At least 24 months post randomisation

Title

Occurrence of possible, probable, or definite TB, or death

Description

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.

Time Frame

At least 24 months post randomisation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Issa Sabi, MD, MMed, PhD

Phone

+255 25 250 3364

isabi@nimr-mmrc.org

First Name & Middle Initial & Last Name or Official Title & Degree

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

Phone

+255 25 250 3364

nelias@nimr-mmrc.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

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

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Nyasatu Chamba, MD.

Organizational Affiliation

Kilimanjaro Christian Medical Centre,Moshi,Tanzania

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

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

Organizational Affiliation

Makerere University, Makerere, Uganda

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Davis Kibirige, MD, Ph.D.

Organizational Affiliation

Martyrs Hospital Lubaga, Makerere, Uganda

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mbeya zonal referral hospital

City

Mbeya

Country

Tanzania

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nyanda E Ntinginya, MD, MSc, PhD

nelias@nimr-mmrc.org

First Name & Middle Initial & Last Name & Degree

Issa Sabi, MD, MMed, PhD

isabi@nimr-mmrc.org

Facility Name

Kilimanjaro Christian Medical Center

City

Moshi

Country

Tanzania

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nyasatu Chamba, MD, MMed

nyasatuchamba@yahoo.com

First Name & Middle Initial & Last Name & Degree

Kajiru Kilonzo, MD, MMed

k.kilonzo@kcri.ac.tz

Facility Name

Makerere University

City

Kampala

Country

Uganda

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Irene Andia- Biraro, MD, MMed, PhD

andiaodanga@yahoo.com

Facility Name

Martyrs Hospital Lubaga

City

Kampala

Country

Uganda

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Davis Kibirige, MD, MMed, PhD

kibirigedavis@gmail.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

35689272

Citation

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.

Results Reference

derived

PubMed Identifier

34505132

Citation

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.

Results Reference

derived

Learn more about this trial

Preventive Treatment Of Latent Tuberculosis Infection In People With Diabetes Mellitus

We'll reach out to this number within 24 hrs