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

NCT01761201 | Terminated Phase 3

• 2 other identifiers: FLISH-ILT2010-022302-41
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 18

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.

Conditions

Latent Tuberculosis Infection; Infection in Solid Organ Transplant Recipients

Keywords

Prophylaxis; Tuberculosis; Transplant recipients; Transplant waiting list

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Mortality

  18 months

• Toxicity

  During all the 18 months of follow-up

• Retransplantation

  18 months

• Graft dysfunction

  18 months

• Transplant rejection

  18 months

Other Outcomes (1)

• Safety

  18 months

Study Arms (2)

levofloxacin

EXPERIMENTAL

Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant

Drug: Levofloxacin

Isoniazid

ACTIVE COMPARATOR

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

Interventions

Levofloxacin DRUG

Levofloxacin

Also known as: Generic name: Levofloxacin, ATC Code: J01MA., Pharmaceutical form: Levofloxacin 500 mg film-coated tablets

levofloxacin

Isoniazid DRUG

300 mg/day for 9 months beginning after transplantation, when the "liver function is stable" and not before 3 months nor after 6 months.

Also known as: Generic name: Isoniazid., ATC Code: J04AC, Pharmaceutical form: tablets.

Isoniazid

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Spanish Network for Research in Infectious Diseases: collaborator

Study Sites (18)

Complejo Hospitalario Universitario

A Coruña, Spain

Location

Complejo Hospitalario de Albacete

Albacete, Spain

Location

Hospital Infanta Cristina,

Badajoz, Spain

Location

Hospital Clinic

Barcelona, Spain

Location

Hospital Vall d'Hebron

Barcelona, Spain

Location

Hospital de Cruces

Bilbao, Spain

Location

Hospital Reina Sofía

Córdoba, Spain

Location

Hospital universitario Virgen de las Nieves

Granada, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Gregorio Marañón

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, Spain

Location

Hospital Universitario Carlos Haya

Málaga, Spain

Location

Hospital Virgen de la Arrixaca

Murcia, Spain

Location

Clínica Universitaria de Navarra

Pamplona, Spain

Location

Hospital Marqués de Valdecillas

Santander, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

Related Publications (2)

• 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.

  PMID: 19445585 BACKGROUND

• 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.

  PMID: 9158022 BACKGROUND

Related Links

• official web site for the Spanish Infectious Disease Network

MeSH Terms

Conditions

Latent Tuberculosis; Tuberculosis

Interventions

Levofloxacin; Isoniazid

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Julián de la Torre Cisneros, MD

  Hospital Universitario Reina Sofía, Córdoba, Spain

  PRINCIPAL INVESTIGATOR

• José M. Aguado, MD, PhD

  Hospital Universitario 12 de Octubre, Madrid

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2013
• First Posted: January 4, 2013
• Study Start: January 1, 2012
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: August 6, 2014

Record last verified: 2014-08

Locations

ES (18)