"Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients". (FLISH-ILT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor:
Collaborator:
Spanish Network for Research in Infectious Diseases
Information provided by (Responsible Party):
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
ClinicalTrials.gov Identifier:
NCT01761201
First received: January 3, 2013
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Latent Tuberculosis Infection
Infection in Solid Organ Transplant Recipients
Drug: Levofloxacin
Drug: Isoniazid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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".

Resource links provided by NLM:


Further study details as provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:

Primary Outcome Measures:
  • Difference in incidence of tuberculosis disease [ Time Frame: 18 months of follow-up ] [ Designated as safety issue: No ]
    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:
  • Mortality [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Number of deaths of any cause

  • Toxicity [ Time Frame: During all the 18 months of follow-up ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    A new liver transplantation during the follow-up

  • Graft dysfunction [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Development of advanced graft fibrosis stages 3 and 4

  • Transplant rejection [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up.


Other Outcome Measures:
  • Safety [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

    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.



Estimated Enrollment: 870
Study Start Date: January 2012
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: levofloxacin
Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant
Drug: Levofloxacin
Levofloxacin
Other Names:
  • Generic name: Levofloxacin
  • ATC Code: J01MA.
  • Pharmaceutical form: Levofloxacin 500 mg film-coated tablets
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
Drug: 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.
Other Names:
  • Generic name: Isoniazid.
  • ATC Code: J04AC
  • Pharmaceutical form: tablets.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761201

Locations
Spain
Complejo Hospitalario de Albacete Recruiting
Albacete, Spain
Contact: Jose Mª Moreno Planas, MD.PhD       josemariamoren@yahoo.es   
Principal Investigator: José María Moreno Planas, MD.PhD         
Hospital Infanta Cristina, Recruiting
Badajoz, Spain
Contact: Agustín Muñoz Sanz, MD.PhD       Agus.muñozsanz@gmail.com   
Principal Investigator: Agustín Muñoz Sanz, MD.PhD         
Hospital Vall d'Hebron Recruiting
Barcelona, Spain
Contact: Oscar Len, MD.PhD       olen@ir.vhebron.net   
Principal Investigator: Oscar Len, MD.PhD         
Hospital Clinic Recruiting
Barcelona, Spain
Contact: Asunción Moreno, MD.PhD       amoreno@clinic.ub.es   
Principal Investigator: Asunción Moreno, MD.PhD         
Hospital de Cruces Recruiting
Bilbao, Spain
Contact: Miguel Montejo, MD.PhD       josemiguel.montejobaranda@osakidetza.net   
Principal Investigator: Miguel Montejo, MD.PhD         
Complejo Hospitalario Universitario Recruiting
Coruña, Spain
Contact: Enrique Miguez, MD.PhD       Enrique.miguez.rey@sergas.es   
Principal Investigator: Enrique Miguez, MD.PhD         
Hospital Reina Sofía Recruiting
Córdoba, Spain
Contact: Elisa Vidal, Md.PhD    +34 011636957    Vidal.elisa@gmail.com   
Principal Investigator: Elisa Vidal, Md.PhD         
Hospital universitario Virgen de las Nieves Recruiting
Granada, Spain
Contact: Miguel Angel López Ruz, MD.PhD       mangel.lopez.sspa@juntadeandalucia.es   
Principal Investigator: Miguel Angel López Ruz, MD.PhD         
Hospital Gregorio Marañón Recruiting
Madrid, Spain
Contact: Patricia Muñoz       pmunoz@hggm.es   
Principal Investigator: Patricia Muñoz, MD.PhD         
Hospital Ramón y Cajal Recruiting
Madrid, Spain
Contact: Pilar Martín Dávila, MD.PhD       pmartin.hrc@salud.madrid.org   
Principal Investigator: Pilar Martín Dávila, MD.PhD         
Hospital 12 de Octubre Recruiting
Madrid, Spain
Contact: Rafael san Juan, MD.PhD       rafasjg@yahoo.es   
Principal Investigator: Rafael San Juan, MD.PhD         
Hospital Universitario Puerta de Hierro Recruiting
Madrid, Spain
Contact: Isolina Baños Pérez, MD.PhD       isolina6@hotmail.com   
Principal Investigator: Isolina Baños Pérez, MD.PhD         
Hospital Virgen de la Arrixaca Recruiting
Murcia, Spain
Contact: José Antonio Pons Miñano, MD.PhD       joseapons@yahoo.es   
Principal Investigator: José Antonio Pons Miñano, MD.PhD         
Hospital Universitario Carlos Haya Recruiting
Málaga, Spain
Contact: Juan Rodrigo, MD.PhD       juan.rodrigo.sspa@juntadeandalucia.es   
Principal Investigator: Juan Rodrigo, MD.PhD         
Clínica Universitaria de Navarra Recruiting
Pamplona, Spain
Contact: José Ignacio Herrero Santos, MD.PhD       iherrero@unav.es   
Principal Investigator: José Ignacio Herrero Santos, MD.PhD         
Hospital Marqués de Valdecillas Recruiting
Santander, Spain
Contact: Carmen Fariñas, MD.PhD       mirfac@humv.es   
Principal Investigator: Carmen Fariñas, MD.PhD         
Hospital Virgen del Rocío Recruiting
Seville, Spain
Contact: Elisa Cordero Matía, MD.PhD       mariae.cordero.sspa@juntadeandalucia.es   
Principal Investigator: Elisa Cordero Matía, MD.PhD         
Hospital Universitario La Fe Recruiting
Valencia, Spain
Contact: Mario Blanes, MD.PhD       mblanes@ono.com   
Principal Investigator: Mario Blanes, MD.PhD         
Sponsors and Collaborators
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Spanish Network for Research in Infectious Diseases
Investigators
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
  More Information

Publications:
Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
ClinicalTrials.gov Identifier: NCT01761201     History of Changes
Other Study ID Numbers: FLISH-ILT, 2010-022302-41
Study First Received: January 3, 2013
Last Updated: October 16, 2013
Health Authority: Spain: Spanish Agency of Medicines

Keywords provided by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla:
Prophylaxis
Tuberculosis
Transplant recipients
Transplant waiting list

Additional relevant MeSH terms:
Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Isoniazid
Ofloxacin
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Lipid Regulating Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Infective Agents, Urinary
Renal Agents

ClinicalTrials.gov processed this record on July 23, 2014