Safety of Rifampicin at High Dose for the Treatment of Adult Subjects with Complex Drug Susceptible Pulmonary and Extrapulmonary Tuberculosis
- Conditions
- 10028440Tuberculosis
- Registration Number
- NL-OMON52031
- Lead Sponsor
- Vall dHebron University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 40
The participant must fulfill either criteria nr. 1-4 AND nr. 5 OR criteria nr.
1-4 AND 6, AND anyone of 7-14:
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)
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
Subjects will be excluded from entry if ANY ONE of the criteria listed below is
met:
1. Rifampicin resistance confirmation.
2. Barthel index < 40 for subjects older than 60 years old.
3. Signs of liver disease not related to TB [Liver enzymes (AST or ALT) > 5x
upper limit of normal , Total bilirubin > 5x upper limit of normal, Patients
with a Child-Pugh grade C cirrhosis or acute decompensation of their chronic
liver disease at enrolment.]
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.
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 the protocol.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary safety endpoint: the proportion of participants with one or more SAE<br /><br>(grade 3 or superior) at the end of the intensive phase (first 8 weeks of<br /><br>treatment).</p><br>
- Secondary Outcome Measures
Name Time Method