"Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients". (FLISH-ILT)
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.
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.
|Latent Tuberculosis Infection Infection in Solid Organ Transplant Recipients||Drug: Levofloxacin Drug: Isoniazid||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||"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".|
- Difference in incidence of tuberculosis disease [ Time Frame: 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.
- Mortality [ Time Frame: 18 months ]Number of deaths of any cause
- Toxicity [ Time Frame: 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 [ Time Frame: 18 months ]A new liver transplantation during the follow-up
- Graft dysfunction [ Time Frame: 18 months ]Development of advanced graft fibrosis stages 3 and 4
- Transplant rejection [ Time Frame: 18 months ]The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up.
- Safety [ Time Frame: 18 months ]
Drug tolerance will be evaluated by a clinical study interview and periodic analytical determinations which will include levels of transaminases (ALT and AST), alkaline phosphatase and gamma-GT, bilirubin, according to the study visit schedule.
All symptoms and laboratory results will be evaluated for severity according to the grading (severity) scale of the National Cancer Institute Common Toxicity Criteria Version 3.0, NCI-CTC-AE v 3.0.
|Study Start Date:||January 2012|
|Study Completion Date:||February 2014|
|Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant
Active Comparator: 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
300 mg/day for 9 months beginning after transplantation, when the "liver function is stable" and not before 3 months nor after 6 months.
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.
- To demonstrate that the efficacy of levofloxacin is not limited by adverse effects, paying particular attention to hepatotoxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01761201
|Complejo Hospitalario de Albacete|
|Hospital Infanta Cristina,|
|Hospital Vall d'Hebron|
|Hospital de Cruces|
|Complejo Hospitalario Universitario|
|Hospital Reina Sofía|
|Hospital universitario Virgen de las Nieves|
|Hospital 12 de Octubre|
|Hospital Gregorio Marañón|
|Hospital Ramón y Cajal|
|Hospital Universitario Puerta de Hierro|
|Hospital Virgen de la Arrixaca|
|Hospital Universitario Carlos Haya|
|Clínica Universitaria de Navarra|
|Hospital Marqués de Valdecillas|
|Hospital Virgen del Rocío|
|Hospital Universitario La Fe|
|Principal Investigator:||Julián de la Torre Cisneros, MD||Hospital Universitario Reina Sofía, Córdoba, Spain|
|Study Chair:||José M. Aguado, MD, PhD||Hospital Universitario 12 de Octubre, Madrid|