Infection in Solid Organ Transplant Recipients, Latent Tuberculosis Infection
Conditions
Keywords
Prophylaxis, Tuberculosis, Transplant recipients, Transplant waiting list
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.
Interventions
DRUGLevofloxacin
Levofloxacin
DRUGIsoniazid
300 mg/day for 9 months beginning after transplantation, when the liver function is stable and not before 3 months nor after 6 months.
Sponsors
Spanish Network for Research in Infectious Diseases
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in incidence of tuberculosis disease | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | 18 months | Number of deaths of any cause |
| Toxicity | 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. |
| Graft dysfunction | 18 months | Development of advanced graft fibrosis stages 3 and 4 |
| Transplant rejection | 18 months | The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up. |
| Retransplantation | 18 months | A new liver transplantation during the follow-up |
Other
| Measure | Time frame | Description |
|---|---|---|
| Safety | 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. |
Countries
Spain
Outcome results
None listed