Treatment of Latent Tuberculosis in Socially Marginalised Citizens (DOT-LTBI)

A Randomised Controlled Trial of a 12-dose Rifapentine and Isoniazid (RPT+INH) Regimen Using Direct Observed Therapy (DOT) Versus 6 Months of Daily Isoniazid for Latent Tuberculosis Infection (LTBI) in Socially Marginalised People

An open-label, randomised controlled trial comparing compliance to treatment for latent tuberculosis infection in socially marginalised citizens. Participants will be randomized to either daily isoniazid for 6 months or weekly rifapentine and isoniazid as directly observed therapy for twelve weeks.

Study Overview

• Status: Terminated
• Conditions: Compliance, Patient
• Intervention / Treatment: Drug: Rifapentine; Drug: Isoniazid

Detailed Description

Eligible participants will be randomised to receive either daily isoniazid for 6 months with monthly visits for pill count, evaluation of adverse events and dispensing of isoniazid for the next month, or weekly doses of rifapentine and isoniazid for twelve weeks as direct observed therapy where the drugs are administered in the presence of a study nurse or doctor.

Control bloodsamples (ALAT, alkaline phosphatase, bilirubin, INR, haemoglobin, trombocytes and leukocyte differential count) will be taken at baseline and at least once during treatment in the rifapentine and isoniazid group and at least twice in the isoniazid-only group.

One year after treatment completion participants will be called in for evaluation for active tuberculosis.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Nina B Staerke, MD; Phone Number: 004523647984; Email: ninase@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Dept of pulmonary medicine
  • Esbjerg, Denmark, 6700
    • Dept of pulmonary medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Reporting to be homeless (independent of whether the person has an official address) or regularly seeking homeless shelters or public institutions to supply basic needs
• LTBI defined by positive IGRA test
• Found plausible by study doctor that the person has been exposed to tuberculosis within 2 years
• Aged 18 years or older

Exclusion Criteria:

• Previously treated for tuberculosis
• Pregnant or breastfeeding
• Active tuberculosis (evaluated by chest x-ray and examination by a trained doctor)
• Unable to give informed consent
• Tested positive for LTBI as part of contact investigation where the index case has or is suspected to have INH of RIF resistant TB
• Known HIV on antiretroviral treatment
• Porphyria
• Known allergy to rifamycins or isoniazid
• Known epilepsy
• Known liver disease causing affected liver parameters (ALAT, alkaline phosphatase, bilirubin, INR)
• Any lab abnormality, disease, concomitant medication or condition that, in the opinion of the investigator, excludes a person from participating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RPT-INH; Participants treated with weekly rifapentine and isoniazid for twelve weeks.	Drug: Rifapentine; Treatment with weekly rifapentine and isoniazid as Directly Observed Therapy in 12 weeks; Other Names: isoniazid; Drug: Isoniazid; Treatment with daily isoniazid in 6 months
Active Comparator: control; Participants treated with daily isoniazid for six months	Drug: Isoniazid; Treatment with daily isoniazid in 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adherence	adherence to treatment in the two groups measured by counting number of pills taken in each group.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
active tuberculosis	active tuberculosis within the study period. In case of suspected tuberculosis during the study the participant will be refered for examination by specialists. At 1 year follow-up participants will have a chest x-ray and physical examination by study doctor to screen for signs of active tuberculosis. If active tuberculosis is suspected further examinations will be performed by specialists.	5 years
adverse events	for both groups all adverse events will be recorded	2 years

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Investigators: Principal Investigator: Christian Wejse, MD PHD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2017
• Primary Completion (Actual): February 9, 2023
• Study Completion (Actual): February 9, 2023

Study Registration Dates

• First Submitted: August 11, 2017
• First Submitted That Met QC Criteria: August 28, 2017
• First Posted (Actual): August 30, 2017

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis; Latent Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; Anti-Bacterial Agents; Leprostatic Agents; Antitubercular Agents; Antibiotics, Antitubercular; Fatty Acid Synthesis Inhibitors; Rifapentine; Isoniazid
• Other Study ID Numbers: A101A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No