"Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients". (FLISH-ILT)
This study is currently recruiting participants.
Verified January 2013 by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor:
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
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: January 4, 2013
Last verified: January 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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:
|
|
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:
|
Detailed Description:
Primary Objective
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
- 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
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
Additional 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: | January 4, 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 May 19, 2013