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

This study has been terminated.
(Recruitment rythm not sufficent to reach the simple size needed.)
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: August 5, 2014
Last verified: August 2014
  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.



Enrollment: 68
Study Start Date: January 2012
Study Completion Date: February 2014
Primary Completion Date: February 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
Albacete, Spain
Hospital Infanta Cristina,
Badajoz, Spain
Hospital Vall d'Hebron
Barcelona, Spain
Hospital Clinic
Barcelona, Spain
Hospital de Cruces
Bilbao, Spain
Complejo Hospitalario Universitario
Coruña, Spain
Hospital Reina Sofía
Córdoba, Spain
Hospital universitario Virgen de las Nieves
Granada, Spain
Hospital Universitario Puerta de Hierro
Madrid, Spain
Hospital Gregorio Marañón
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital 12 de Octubre
Madrid, Spain
Hospital Virgen de la Arrixaca
Murcia, Spain
Hospital Universitario Carlos Haya
Málaga, Spain
Clínica Universitaria de Navarra
Pamplona, Spain
Hospital Marqués de Valdecillas
Santander, Spain
Hospital Virgen del Rocío
Seville, Spain
Hospital Universitario La Fe
Valencia, Spain
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: August 5, 2014
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:
Communicable Diseases
Infection
Latent Tuberculosis
Tuberculosis
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections
Isoniazid
Levofloxacin
Ofloxacin
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimetabolites
Antineoplastic Agents
Antitubercular Agents
Enzyme Inhibitors
Fatty Acid Synthesis Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Renal Agents
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 22, 2014