Clinical trial NCT01761201: "Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients".
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".
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Latent Tuberculosis Infection
Infection in Solid Organ Transplant Recipients
Keywords: Prophylaxis
Tuberculosis
Transplant recipients
Transplant waiting list
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Spanish Network for Research in Infectious Diseases
First posted: 2013-01-04
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Difference in incidence of tuberculosis disease
timeFrame: 18 months of follow-up
Secondary outcomes:
measure: Mortality
timeFrame: 18 months
measure: Toxicity
timeFrame: During all the 18 months of follow-up
measure: Retransplantation
timeFrame: 18 months
measure: Graft dysfunction
timeFrame: 18 months
measure: Transplant rejection
timeFrame: 18 months
Other outcomes:
measure: Safety
timeFrame: 18 months
Locations:
city: Albacete
country: Spain
facility: Complejo Hospitalario de Albacete
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina,
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Bilbao
country: Spain
facility: Hospital de Cruces
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Granada
country: Spain
facility: Hospital universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro
city: Murcia
country: Spain
facility: Hospital Virgen de la Arrixaca
city: Málaga
country: Spain
facility: Hospital Universitario Carlos Haya
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
city: Santander
country: Spain
facility: Hospital Marqués de Valdecillas
city: Seville
country: Spain
facility: Hospital Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
Study officials:
affiliation: Hospital Universitario Reina Sofía, Córdoba, Spain
name: Julián de la Torre Cisneros, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital Universitario 12 de Octubre, Madrid
name: José M. Aguado, MD, PhD
role: STUDY_CHAIR
References:
citation: Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, Cervera C, Len O, Carratala J, Cisneros JM, Bou G, Munoz P, Ramos A, Gurgui M, Borrell N, Fortun J, Moreno A, Gavalda J; Spanish Network for Research in Infectious Diseases. Tuberculosis after solid-organ transplant: incidence, risk factors, and clinical characteristics in the RESITRA (Spanish Network of Infection in Transplantation) cohort. Clin Infect Dis. 2009 Jun 15;48(12):1657-65. doi: 10.1086/599035.
citation: Aguado JM, Herrero JA, Gavalda J, Torre-Cisneros J, Blanes M, Rufi G, Moreno A, Gurgui M, Hayek M, Lumbreras C, Cantarell C. Clinical presentation and outcome of tuberculosis in kidney, liver, and heart transplant recipients in Spain. Spanish Transplantation Infection Study Group, GESITRA. Transplantation. 1997 May 15;63(9):1278-86. doi: 10.1097/00007890-199705150-00015.