AN INTERNATIONAL MULTICENTRE CONTROLLED CLINICAL TRIAL TO EVALUATE 1200MG AND 1800MG RIFAMPICIN DAILY IN THE REDUCTION OF TREATMENT DURATION FOR PULMONARY TUBERCULOSIS FROM 6 MONTHS TO 4 MONTHS (RIFASHORT)

• Register: RPEC
• Last refreshed on: 4 September 2023
• Main ID: PER-007-17
• Date of registration: 26/06/2017
• Prospective Registration: Yes
• Primary sponsor: St Georges University of London,
• Public title: AN INTERNATIONAL MULTICENTRE CONTROLLED CLINICAL TRIAL TO EVALUATE 1200MG AND 1800MG RIFAMPICIN DAILY IN THE REDUCTION OF TREATMENT DURATION FOR PULMONARY TUBERCULOSIS FROM 6 MONTHS TO 4 MONTHS (RIFASHORT)
• Scientific title: AN INTERNATIONAL MULTICENTRE CONTROLLED CLINICAL TRIAL TO EVALUATE 1200MG AND 1800MG RIFAMPICIN DAILY IN THE REDUCTION OF TREATMENT DURATION FOR PULMONARY TUBERCULOSIS FROM 6 MONTHS TO 4 MONTHS (RIFASHORT)
• Date of first enrolment: 31/03/2021
• Target sample size: 200
• Recruitment status: Complete
• URL: https://www.ins.gob.pe/ensayosclinicos/rpec/recuperarECPBNuevoEN.asp?numec=007-17
• Study type: Interventional
• Study design: An open-label 3-arm trial to compare a standard 6-month control regimen with two 4-month treatment regimens for the treatment of tuberculosis (TB).
• Phase: III

Countries of recruitment

Bolivia, Botswana, Peru, Uganda

Contacts

• Name: Eduardo Romulo Chavez Ticona
• Affiliation: Tropical Levir S.A.C.

• Name: Eduardo Romulo Chavez Ticona
• Affiliation: Tropical Levir S.A.C.

Key inclusion & exclusion criteria

Inclusion criteria:
Patient inclusion criteria
1. Patients with:
a) Newly diagnosed, smear microscopy positive, pulmonary tuberculosis, rifampicin susceptible MTBC confirmed by Xpert MTB/RIF
OR
b) Smear microscopy negative, suspected pulmonary tuberculosis, confirmed by Xpert MTB/RIF as sputum MTBC positive and rifampicin susceptible
2. No more than one week of previous treatment for tuberculosis, for either active TB or treatment of confirmed or presumed latent TB infection.
3. Patients ≥ 18 years old
4. Consent to participation in the trial and to HIV testing
5. Provide informed consent.
6. Patient has a stable home address within easy reach of the treatment facility and likely to remain there for the entire treatment and follow-up period.
7. Women who are pre-menopausal or of a child-bearing age must be using a barrier form of contraception (condoms, diaphragms, cervical caps, or contraceptive sponges), be surgically sterilised or have an intrauterine coil device (IUCD) in place for the duration of the treatment phase, alternatively they should agree to abstain from sexual activity during the treatment phase.

Exclusion criteria:
1. Patients with rifampicin resistance identified by Xpert MTB/RIF or by direct susceptibility testing (late exclusions).
2. Patient is in a moribund phase.
3. Has TB meningitis or extra-pulmonary TB.
4. Is female and known to be pregnant, or breast feeding.
5. Is suffering from a condition likely to lead to uncooperative behaviour such as psychiatric illness or alcoholism.
6. Has a history of seizures
7. Has contraindications to any medications in the study regimens
8. Is HIV positive according to local testing algorithm
9. Has a blood disorder (including grade 4 or above thrombocytopenia)
10. Haemoglobin <7g/dl
11. Has peripheral neuritis
12. Has pre-existing liver disease
13. ALT > 5 times the upper limit of normal (ULN) for that laboratory
14. Raised Bilirubin (grade 4 or above)
15. Has kidney disease
16. Estimated Creatinine clearance of < 30mls/min. Calculated using the Cockcroft Gault Formula: CrCl (mL/min) = N x [140-age (years)] x weight (kg) Serum creatinine (micromol/L) Where N = 1.23 males, 1.04 females
17. Previously diagnosed diabetes mellitus (non-insulin dependent or insulin dependent)
18. HbA1C >48mmol/mol
19. Weight < 35kg
20. Patient is taking any of the excluded medications listed in the Summary of Product Characteristics (SmPC) for any trial drugs
21. Has other pre-existing non-tuberculous disease likely to prejudice the response to, or assessment of, treatment as judged by the Principal Investigator.


Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

-A150 Tuberculosis of lung, confirmed by sputum microscopy with or without culture
Tuberculosis of lung, confirmed by sputum microscopy with or without culture

Tuberculosis of lung, confirmed by sputum microscopy with or without culture

A150

Intervention(s)

Patients enrolled in the trial will be randomly allocated to receive one of the following three chemotherapy treatment regimens:
1. Control regimen (R10): The standard regimen of isoniazid, pyrazinamide and ethambutol plus 10 mg/kg rifampicin for the initial 8 weeks, followed by isoniazid and rifampicin (at the same dose size) for an additional 4 months (2HRZE/4HR).
2. Study regimen 1(SR1): 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70 and more kg) of rifampicin will be given throughout the four months (2EHR 1200Z/2HR1200)
3. Study regimen 2(SR2): 2 months of daily ethambutol, isoniazid, rifampicin, and pyrazinamide followed by 2 months of daily isoniazid and rifampicin. A supplement of either 450 mg (weight bands 35-39kg and 40-54kg) or 600mg (weight band 55-69kg and 70 and more kg) of rifampicin will be given throughout the four months (2EHR1800Z/2HR1800).

Secondary ID(s)

NCT02581527

Source(s) of Monetary Support

MRC’s Global Health Trials Scheme

Ethics review

Status: Approved
Approval date: 18/08/2016
Contact:

[e-mail]

Hospital Nacional Dos de Mayo

3280028

[e-mail]

Results

• Results available: Yes
• Date Completed: 23/08/2021