Pragmatic Optimized Rifampicin Trial

Tuberculosis, Pulmonary Clinical Trial

— PORT  

Official title:

Pragmatic Trial on the Safety and Tolerability of an Optimized Dose of Rifampicin in Tuberculosis Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06057519
• Other study ID #: PORT- 01
• Status: Recruiting
• Phase: Phase 3
• Start date: January 16, 2024
• Est. completion date: December 31, 2025

Study information

• Verified date: May 2023
• Source: Radboud University Medical Center
• Contact: Jodie Schilkdraut, PhD
• Phone: +31 629677680
• Email: Jodie.schildkraut[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 164
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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
• Serum total bilirubin level >2.5 times the upper limit of normal
• Creatinine clearance (CrCl) level lower than 30 mls/min
• Acute or severe or life-threatening liver disease induced by drugs in the past
• The patient has a chronic disorder such as liver disease or renal disease.
• The patient has icterus.
• Previous anti-TB treatment: the patient ended a previous TB treatment (episode) within last 3 months.

Related Conditions & MeSH terms

• Tuberculosis
• Tuberculosis, Pulmonary

Intervention

Drug:
• Optimised dose rifampicin
Optimized dose of rifampicin
• Standard dose rifampicin
Standard dose rifampicin

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of hepatotoxicity	How often does hepatotoxicity occur in patients with optimized dose rifampicin vs standard dose rifampicin	26 weeks
Secondary	Adverse events	The proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin will be compared between treatment arms.	26 weeks
Secondary	Treatment outcome	Final treatment outcome at the end of treatment according to WHO definitions of cure will be compared between treatment arms	26 weeks
Secondary	Culture conversion rate	Two and three months culture conversion rates will be compared between treatment arms.	2 and 3 months post-treatment initiation
Secondary	PK parameter, AUC0-24	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The AUC0-24 will be determined using sparse PK sampling.	2 Weeks
Secondary	PK parameter, Cmax	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The maximum concentration will be determined using sparse PK sampling.	2 Weeks
Secondary	PK parameter, Tmax	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The time to maximum concentration will be determined using sparse PK sampling.	2 Weeks
Secondary	PK parameter, Clearance	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The clearance of rifampicin will be determined using sparse PK sampling.	2 Weeks
Secondary	PK parameter, Volume of distribution	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The volume of distribution of rifampicin will be determined using sparse PK sampling.	2 Weeks
Secondary	PK parameter, T1/2	Steady-state plasma pharmacokinetic parameters will be compared between treatment arms. The half life of rifampicin will be determined using sparse PK sampling.	2 Weeks