Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients.

Study Overview
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Brief Summary
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A multicenter, prospective, non-inferiority, randomized and open clinical trial comparing levofloxacin with isoniazid in the treatment of latent tuberculosis infection in patients eligible for liver transplantation. Patients over 18 years of age on the waiting list for liver transplantation. Sample size: n=870 patients. HYPOTHESIS Levofloxacin treatment of latent tuberculosis infection, begun while on the waiting list for liver transplantation, is safer and not less effective than isoniazid treatment begun after transplantation when liver function is stable.

Detailed Description
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Primary Objective To demonstrate that the incidence of tuberculosis in patients with latent tuberculosis infection and treated with levofloxacin is not higher than that observed in patients treated with isoniazid. Secondary Objective To demonstrate that the efficacy of levofloxacin is not limited by adverse effects, paying particular attention to hepatotoxicity.

Official Title
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A Prospective, Randomized, Comparative Clinical Trial of the Efficacy and Safety of Levofloxacin Versus Isoniazid in the Treatment of Latent Tuberculosis Infection in Liver Transplant Patients.

Conditions
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Latent Tuberculosis Infection, Infection in Solid Organ Transplant Recipients

Intervention / Treatment
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* Drug: Levofloxacin
* Drug: Isoniazid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver transplantation candidates with age ≥ 18 years, no clinical or radiological evidence of active tuberculosis and negative pregnancy test (if applicable)who must meet one or more of the following criteria: PPD skin test (initial or after a booster effect) >5 mm. Alternatively, the determination may be made by the interferon gamma (IFN-g) production in PPD-stimulated lymphocytes using the Quantiferon-TB or ELISPOT assays. Past history of tuberculosis not properly treated. Past history of contact with a patient with active TB. Chest x-ray consistent with past untreated TB (apical fibronodular lesions, calcified solitary nodule, calcified lymph nodes or pleural thickening). The patient must give their written informed consent. Exclusion Criteria: Lack of consent to participate in the study. Intolerance or allergy to levofloxacin or to isoniazid. Documented contact with tuberculosis resistant to levofloxacin or to isoniazid. Treatment in the previous month with drugs with potential activity against Mycobacterium tuberculosis, (especially quinolones).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: levofloxacin<br>Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant | Drug: Levofloxacin<br>* Levofloxacin<br>* Other names: Pharmaceutical form: Levofloxacin 500 mg film-coated tablets;|
| Active Comparator: Isoniazid<br>Isoniazid 300 mg/day for 9 months beginning after transplantation, when the liver function is stable and not before 3 months nor after 6 months | Drug: Isoniazid<br>* 300 mg/day for 9 months beginning after transplantation, when the liver function is stable and not before 3 months nor after 6 months.<br>* Other names: Pharmaceutical form: tablets.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in incidence of tuberculosis disease | A patient will be considered as having tuberculosis when Mycobacterium tuberculosis is isolated by culture or M. Tuberculosis DNA is isolated from a representative clinical sample, organ fluid or tissue by polymerase chain reaction. Also cases of histopathologically confirmed tuberculosis (caseating granulomas with/without demonstration of acid-alcohol resistant bacillus [BAAR]) and clinically compatible presentation will be accepted. Tuberculosis will be classified as pulmonary (pulmonary parenchymal involvement), extrapulmonary (involvement of different organs to the lung) or disseminated (involvement of at least two non-contiguous organs). Cases where tuberculosis is diagnosed on the basis of clinical and/or radiology suspicion and for whom the corresponding physician has prescribed a specific treatment will not be accepted. | 18 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Number of deaths of any cause | 18 months | 
| Toxicity | Occurrence of grade 3 or 4 toxicities according to the grading (severity) scale of the National Cancer Institute Common Toxicity Criteria Version 4.0, NCI-CTC-AE v 4.0. | During all the 18 months of follow-up | 
| Retransplantation | A new liver transplantation during the follow-up | 18 months | 
| Graft dysfunction | Development of advanced graft fibrosis stages 3 and 4 | 18 months | 
| Transplant rejection | The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prophylaxis, Tuberculosis, Transplant recipients, Transplant waiting list