Pragmatic Optimized Rifampicin Trial

NCT06057519 | Recruiting Phase 3 DMC

• 1 other identifier: PORT- 01
• Study Type: interventional
• Target: 164
• Locations: 2 countries
• Sites: 2

Brief Summary

The goal of this clinical trial is to compare an optimized dose (1800 mg) of rifampicin to standard dose (450 mg if patient \<50 kg and 600 mg if patient \>50kg) of rifampicin in tuberculosis patients. The main questions it aims to answer are:

• To compare the incidence of hepatotoxicity occurs in the optimized dose vs standard dose arm
• To compare any adverse events occur in the optimized dose vs standard dose arm
• To compare final treatment outcome at the end of treatment according to WHO definitions of cure in the optimized dose regimen versus the standard dose regimen.
• To compare two and three months culture conversion rates in the optimized dose regimen versus the standard dose regimen.
• To describe and compare the steady-state plasma pharmacokinetics of the optimized dose regimen versus the standard dose regimen. Participants will be given an optimized dose of 1800 mg of rifampicin daily. Researchers will compare the optimized and standard dose to see if more hepatotoxicity occurs.

Conditions

Tuberculosis, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Incidence of hepatotoxicity

  How often does hepatotoxicity occur in patients with optimized dose rifampicin vs standard dose rifampicin

  26 weeks

Secondary Outcomes (9)

• Adverse events

  26 weeks

• Treatment outcome

  26 weeks

• Culture conversion rate

  2 and 3 months post-treatment initiation

• PK parameter, AUC0-24

  2 Weeks

• PK parameter, Cmax

  2 Weeks

Study Arms (2)

Optimized dose rifampicin

EXPERIMENTAL

1800 mg flat dose

Drug: Optimised dose rifampicin

Standard dose rifampicin

ACTIVE COMPARATOR

450 mg for patients under 50 kg and 600 mg for patients over 50 kg

Drug: Standard dose rifampicin

Interventions

Optimised dose rifampicin DRUG

Optimized dose of rifampicin

Optimized dose rifampicin

Standard dose rifampicin DRUG

Standard dose rifampicin

Standard dose rifampicin

Eligibility Criteria

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

You may qualify if:

• The patient has provided informed consent for study participation prior to all trial-related procedures.
• The patient has a diagnosis of pulmonary tuberculosis according to the local diagnostic criteria.
• The patient is aged 18 years or older at the day of informed consent.
• No known allergic reactions or toxicity to rifampicin in the past.
• Female patients of childbearing potential must have a negative serum pregnancy test, and consent to practice an effective method of birth control during the study. And they should not be lactating during the trial (female participants of childbearing potential only). Effective birth control for female patients has to include two methods, including methods that the patient's sexual partner(s) use. At least one must be a barrier method. Female patients are considered not to be of childbearing potential if they are post-menopausal with no menses for the last 12 months, or surgically sterile (this condition is fulfilled by bilateral oophorectomy, hysterectomy, and by tubal ligation which is done at least 12 months prior to enrolment).
• The patient will be compliant to the study schedule, in the discretion of the investigator.

You may not qualify if:

• The patient has tuberculosis which is assessed to receive high dose rifampicin according to the local standard of care.
• The patient started current TB treatment more than 4 weeks ago.
• The patient has TB meningitis.
• The patient is in a coma.
• Circumstances that raise doubt about free, uncoerced consent to study participation (e.g. in a prisoner or mentally handicapped person)
• The patient is not able to give consent personally.
• Poor general condition or comorbidities where delay in treatment cannot be tolerated or death within three months is likely. Or if there is concurrent treatment that may interfere.
• The patient is pregnant or breast-feeding.
• Patient infected with a rifampicin-resistant strain of M. tuberculosis.
• Known allergy or intolerance for rifamycins.
• The participant has a known or suspected, current alcohol or drug or amphetamine abuse, that is, in the opinion of the investigator, sufficient to compromise the safety or cooperation of the patient.
• The patient has a known allergy or intolerance, or concomitant disorders or conditions for which rifamycins or other standard TB treatment drugs are contraindicated.
• The patient has had treatment with any other investigational drug within 1 month prior to enrolment, or enrolment into other clinical (intervention) trials is planned in the upcoming 6 months
• Laboratory: at screening one or more of the following abnormalities were observed for the patient in screening laboratory:
• Serum amino aspartate transferase (AST) and/or serum alanine aminotransferase (ALT) activity \>3x the upper limit of normal

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (2)

ASL Città di Torino

Turin, Italy

RECRUITING

Radboud University Medical Centre

Nijmegen, Netherlands

RECRUITING

MeSH Terms

Conditions

Tuberculosis, Pulmonary

Interventions

Rifampin

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Martin Boeree

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jodie Schilkdraut, PhD

CONTACT

+31 629677680; Jodie.schildkraut@radboudumc.nl

Iris Spelier

CONTACT

+31 650000985; Iris.spelier@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: September 28, 2023
• Study Start: January 16, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 21, 2026

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); IT (1)