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

Latent Tuberculosis Infection Clinical Trial

— FLISH-ILT  

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".

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01761201
• Other study ID #: FLISH-ILT
• Secondary ID: 2010-022302-41
• Status: Terminated
• Phase: Phase 3
• First received: January 3, 2013
• Last updated: August 5, 2014
• Start date: January 2012
• Est. completion date: February 2014

Study information

• Verified date: August 2014
• Source: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: February 2014
• Est. primary completion date: February 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• Infection
• Infection in Solid Organ Transplant Recipients
• Latent Tuberculosis
• Latent Tuberculosis Infection
• Tuberculosis

Intervention

Drug:
• Levofloxacin
Levofloxacin
• 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.

Locations

Country	Name	City	State
Spain	Complejo Hospitalario de Albacete	Albacete
Spain	Hospital Infanta Cristina,	Badajoz
Spain	Hospital Clinic	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Cruces	Bilbao
Spain	Hospital Reina Sofía	Córdoba
Spain	Complejo Hospitalario Universitario	Coruña
Spain	Hospital universitario Virgen de las Nieves	Granada
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Gregorio Marañón	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Universitario Carlos Haya	Málaga
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Clínica Universitaria de Navarra	Pamplona
Spain	Hospital Marqués de Valdecillas	Santander
Spain	Hospital Virgen del Rocío	Seville
Spain	Hospital Universitario La Fe	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla	Spanish Network for Research in Infectious Diseases

Country where clinical trial is conducted

Spain, 

References & Publications (2)

Aguado JM, Herrero JA, Gavaldá J, Torre-Cisneros J, Blanes M, Rufí G, Moreno A, Gurguí 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. Review. Erratum in: Transplantation 1997 Sep 27;64(6):942. — View Citation

Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, Cervera C, Len O, Carratala J, Cisneros JM, Bou G, Muñoz P, Ramos A, Gurgui M, Borrell N, Fortún 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Safety	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.	18 months	Yes
Primary	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	No
Secondary	Mortality	Number of deaths of any cause	18 months	Yes
Secondary	Toxicity	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.	During all the 18 months of follow-up	Yes
Secondary	Retransplantation	A new liver transplantation during the follow-up	18 months	Yes
Secondary	Graft dysfunction	Development of advanced graft fibrosis stages 3 and 4	18 months	Yes
Secondary	Transplant rejection	The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up.	18 months	Yes

External Links

•   official web site for the Spanish Infectious Disease Network