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

Phase 3

Terminated

• Conditions: Latent Tuberculosis Infection; Infection in Solid Organ Transplant Recipients
• Interventions: Drug: Isoniazid; Drug: Levofloxacin

• Registration Number: NCT01761201
• Lead Sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

Brief Summary

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

Primary Objective

1. 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

2. To demonstrate that the efficacy of levofloxacin is not limited by adverse effects, paying particular attention to hepatotoxicity.

Study Timeline

• Study Start: 2012-01
• Study First Submitted: 2013-01-03
• Study First Submitted QC: 2013-01-03
• Study First Posted: 2013-01-04
• Primary Completion: 2014-02
• Study Completion: 2014-02
• Status Verified: 2014-08
• Last Update Submitted: 2014-08-05
• Last Update Posted: 2014-08-06

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isoniazid	Isoniazid	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
levofloxacin	Levofloxacin	Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant

Primary Outcome Measures

Name	Time	Method
Difference in incidence of tuberculosis disease	18 months of follow-up	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.

Secondary Outcome Measures

Name	Time	Method
Transplant rejection	18 months	The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up.
Toxicity	During all the 18 months of follow-up	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.
Retransplantation	18 months	A new liver transplantation during the follow-up
Graft dysfunction	18 months	Development of advanced graft fibrosis stages 3 and 4
Mortality	18 months	Number of deaths of any cause

Trial Locations

Locations (18)

Complejo Hospitalario de Albacete; 🇪🇸 Albacete, Spain

Hospital Infanta Cristina,; 🇪🇸 Badajoz, Spain

Hospital universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Clínica Universitaria de Navarra; 🇪🇸 Pamplona, Spain

Hospital Universitario Carlos Haya; 🇪🇸 Málaga, Spain

Hospital Universitario Puerta de Hierro; 🇪🇸 Madrid, Spain

Hospital Virgen del Rocío; 🇪🇸 Seville, Spain

Hospital Virgen de la Arrixaca; 🇪🇸 Murcia, Spain

Complejo Hospitalario Universitario; 🇪🇸 Coruña, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clinic; 🇪🇸 Barcelona, Spain

Hospital de Cruces; 🇪🇸 Bilbao, Spain

Hospital Reina Sofía; 🇪🇸 Córdoba, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain

Hospital Marqués de Valdecillas; 🇪🇸 Santander, Spain