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

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ClinicalTrials.gov Identifier: NCT01761201
Recruitment Status : Terminated (Recruitment rythm not sufficent to reach the simple size needed.)
First Posted : January 4, 2013
Last Update Posted : August 6, 2014
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

Tracking Information
First Submitted Date  ICMJE January 3, 2013
First Posted Date  ICMJE January 4, 2013
Last Update Posted Date August 6, 2014
Study Start Date  ICMJE January 2012
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2013)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 3, 2013)
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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE "Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients".
Official Title  ICMJE "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".
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Latent Tuberculosis Infection
  • Infection in Solid Organ Transplant Recipients
Intervention  ICMJE
  • Drug: Levofloxacin
    Levofloxacin
    Other Names:
    • Generic name: Levofloxacin
    • ATC Code: J01MA.
    • Pharmaceutical form: Levofloxacin 500 mg film-coated tablets
  • 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.
Study Arms  ICMJE
  • Experimental: levofloxacin
    Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant
    Intervention: Drug: Levofloxacin
  • 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
    Intervention: Drug: Isoniazid
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 5, 2014)
68
Original Estimated Enrollment  ICMJE
 (submitted: January 3, 2013)
870
Actual Study Completion Date  ICMJE February 2014
Actual Primary Completion Date February 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01761201
Other Study ID Numbers  ICMJE FLISH-ILT
2010-022302-41 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study Sponsor  ICMJE Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Collaborators  ICMJE Spanish Network for Research in Infectious Diseases
Investigators  ICMJE
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
PRS Account Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP