Rifampicin at High Dose for Difficult-to-Treat Tuberculosis
NCT ID: NCT04768231
Last Updated: 2021-02-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE2
130 participants
INTERVENTIONAL
2021-04-01
2023-12-31
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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R35HZE
Participants treated with rifampicin at a dose of 35 mg per kilogram of body weight per day, added to the standard doses of isoniazid, pyrazinamide and ethambutol.
Rifampin
The target dose of 35mg/kg will be reached supplementing fixed-dose combination tablets (standard dose) with rifampin-only tablets.
Interventions
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Rifampin
The target dose of 35mg/kg will be reached supplementing fixed-dose combination tablets (standard dose) with rifampin-only tablets.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
1. Subjects with confirmed or probable pulmonary or extra pulmonary DS-TB.
2. Informed consent provided.
3. Positive smear, positive Xpert® MTB/RIF test, positive M. tuberculosis culture (confirmed cases) OR histological study compatible with necrotizing granulomas OR a liquid biochemistry (pleural, pericardial, ascites or cerebrospinal fluid) suggestive of TB together with clinical symptoms resembling TB disease in the absence of any other possible cause (probable cases).
4. Female participants of childbearing age must have a negative pregnancy test at baseline.
AND
5. Age ≥ 60 years old. OR
6. Age ≥ 18 years AND one of the following
7. Body mass index ≤ 18.5
8. Human Immunodeficiency Virus (HIV) infection.
9. Diabetes Mellitus
10. Hepatitis C virus (HCV) infection (positive HCV serology)
11. Hepatitis B virus (HBV) infection (positive HBV surface antigen or anti-core antibodies)
12. Daily alcohol intake ≥ 2 units of alcohol (1 unit of alcohol: 4% alcohol 250ml (ie beer); 4.5% alcohol 218ml (i.e. cider); 13% alcohol 76ml (i.e. wine); 40% alcohol 25ml (i.e. whisky))
13. Chronic liver disease of any other cause (metabolic, toxic, autoimmune)
14. Central Nervous System TB involvement
Exclusion Criteria
1. Rifampicin resistance confirmation.
2. Barthel index \<40 for subjects older than 60 years old.
3. Signs of significant liver disease:
* Liver enzymes (AST or ALT) \> 5x upper limit of normal
* Total bilirubin \> 3x upper limit of normal
* Subjects with a Child-Pugh grade C cirrhosis or acute decompensation of their chronic liver disease at enrolment.
* Any other grade 3-4 hepatobiliary alteration according to the CTCAE v5.
4. Subjects with known allergy or sensitivity to rifampicin, or any of the other components of DS-TB treatment.
5. Treatment with any of the following: rifampicin, isoniazid, pyrazinamide, ethambutol, levofloxacin, or moxifloxacin within the last month for at least 14 days or current TB treatment for more than 7 days.
6. The subject is enrolled in any other investigational trial that includes a drug intervention.
7. Subjects with solid organ transplantation or bone marrow transplantation.
8. Subjects with an active onco-hematological neoplasm requiring chemotherapy or immune therapy.
9. Previous severe pulmonary disease, other than pulmonary DS-TB, according to local investigator.
10. Pre-existing epilepsy or psychiatric disorder according to local investigator.
11. Ischemic heart disease OR severe arrhythmia within 6 months OR Atrial Fibrillation with oral anticoagulant therapy indication when transitioning to low-molecular weight heparin is not feasible.
12. Positive pregnancy test
13. Breastfeeding women.
14. The subject used any drugs or substances known to be strong inhibitors or inducers of cytochrome P450 enzymes which are involved in the degradation pathways of rifampicin within the time windows specified in table 2.
18 Years
ALL
No
Sponsors
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University Medical Center Groningen
OTHER
Radboud University Medical Center
OTHER
Centro Hospitalar De São João, E.P.E.
OTHER
Instituto Nacional de Enfermedades Respiratorias y del Ambiente, Paraguay
UNKNOWN
Hospital Universitari Vall d'Hebron Research Institute
OTHER
Responsible Party
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Principal Investigators
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Adrián Sánchez-Montalvá, PhD
Role: PRINCIPAL_INVESTIGATOR
Vall d'Hebron University Hospital
Locations
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University Medical Center
Groningen, , Netherlands
Radboud University Medical Center
Nijmegen, , Netherlands
Instituto Nacional de Enfermedades Respiratorias y del Ambiente
Asunción, , Paraguay
Centro Hospitalario Universitario de Sao Joao
Porto, , Portugal
Hospital Universitari Vall d'Hebron. Universitat Autonoma de Barcelona
Barcelona, , Spain
Countries
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Central Contacts
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Facility Contacts
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References
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van Ingen J, Aarnoutse RE, Donald PR, Diacon AH, Dawson R, Plemper van Balen G, Gillespie SH, Boeree MJ. Why Do We Use 600 mg of Rifampicin in Tuberculosis Treatment? Clin Infect Dis. 2011 May;52(9):e194-9. doi: 10.1093/cid/cir184.
Seijger C, Hoefsloot W, Bergsma-de Guchteneire I, Te Brake L, van Ingen J, Kuipers S, van Crevel R, Aarnoutse R, Boeree M, Magis-Escurra C. High-dose rifampicin in tuberculosis: Experiences from a Dutch tuberculosis centre. PLoS One. 2019 Mar 14;14(3):e0213718. doi: 10.1371/journal.pone.0213718. eCollection 2019.
Steingart KR, Jotblad S, Robsky K, Deck D, Hopewell PC, Huang D, Nahid P. Higher-dose rifampin for the treatment of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis. 2011 Mar;15(3):305-16.
Magis-Escurra C, Later-Nijland HM, Alffenaar JW, Broeders J, Burger DM, van Crevel R, Boeree MJ, Donders AR, van Altena R, van der Werf TS, Aarnoutse RE. Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin. Int J Antimicrob Agents. 2014 Sep;44(3):229-34. doi: 10.1016/j.ijantimicag.2014.04.019. Epub 2014 Jun 9.
Espinosa-Pereiro J, Ghimire S, Sturkenboom MGG, Alffenaar JC, Tavares M, Aguirre S, Battaglia A, Molinas G, Tortola T, Akkerman OW, Sanchez-Montalva A, Magis-Escurra C. Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial. Pharmaceutics. 2022 Dec 20;15(1):9. doi: 10.3390/pharmaceutics15010009.
Related Links
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EUSAT consortium website
Other Identifiers
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2020-003146-36
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
RIAlta-1
Identifier Type: -
Identifier Source: org_study_id
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