Pragmatic trial on the safety and tolerability of an optimized dose of rifampicin in tuberculosis patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Radboud University Medical Center

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

15 Jan 2024 → ongoing

Decision date (initial)

2024-01-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Radboudumc

External identifiers

EU CT number

2023-509885-39-00

EudraCT number

2022-000632-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

The primary endpoint is to assess the safety of a higher dose of rifampicin assessed by the incidence of hepatotoxicity compared between treatment arms at the end of the 6 months treatment

Secondary objectives 4

1. To determine the proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin during the 6 months treatment compared between treatment arms.
2. To determine the final treatment outcome at the end of treatment according to WHO definitions of cure compared between treatment arms.
3. To determine the two and three months culture conversion rates compared between treatment arms.
4. To determine the steady-state plasma pharmacokinetic parameters compared between treatment arms.

Conditions and MedDRA coding

Tuberculosis

Study design 1 period

Regulatory references

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The patient has provided informed consent for study participation prior to all trial-related procedures.
2. The patient has a diagnosis of pulmonary tuberculosis according to the local diagnostic criteria.
3. The patient is aged 18 years or older at the day of informed consent.
4. No known allergic reactions or toxicity to rifampicin in the past.
5. 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 lactacting during the trial (female participants of childbearing potential only).
6. The patient will be compliant to the study schedule, in the discretion of the investigator.
7. For France only: the patient is affiliated to a social security system (as beneficiary) or has state medical aid (Aide Médical d’Etat, AME) or has an ongoing demand for state medical aid (AME) or has an ongoing demand for an emergency medical care (dispositif de soins d'urgence, as applicable for tuberculosis).

Exclusion criteria 18

1. The patient has tuberculosis which is assessed to receive high dose rifampicin according to national guidelines.
2. The patient started current TB treatment more than 4 weeks ago.
3. The patient has TB meningitis.
4. The patient is in a coma.
5. Circumstances that raise doubt about free, uncoerced consent to study participation (e.g. in a prisoner or mentally handicapped person).
6. The patient is not able to give consent personally.
7. 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.
8. The patient is pregnant or breast-feeding.
9. Patient infected with a rifampicin-resistant strain of M. tuberculosis.
10. Known allergy or intolerance for rifamycins.
11. 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.
12. The patient has a known allergy or intolerance, or concomitant disorders or conditions for which rifamycins or other standard TB treatment drugs are contraindicated.
13. 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.
14. 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
15. Acute or severe or life-threatening liver disease induced by drugs in the past
16. The patient has a chronic disorder such as liver disease or renal disease.
17. The patient has icterus.
18. Previous anti‐TB treatment: the patient ended a previous TB treatment (episode) within last 3 months.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The incidence of hepatotoxicity

Secondary endpoints 4

1. The proportion of adverse events overall and graded by severity assessed to be related or probably related to rifampicin.
2. Final treatment outcome at the end of treatment according to WHO definitions of cure.
3. Two and three months culture conversion rates
4. Steady-state plasma pharmacokinetic parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Radboud University Medical Center

Sponsor organisation

Stichting Radboud University Medical Center

Address

Geert Grooteplein Zuid 10

City

Nijmegen

Postcode

6525 GA

Country

Netherlands

Scientific contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Jodie Schildkraut

Public contact point

Organisation

Stichting Radboud University Medical Center

Contact name

Jodie Schildkraut

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Application history

3 submissions — initial application plus substantial / non-substantial modifications