Latent Tuberculosis InfectionPhase 3FLISH-ILTNCT01761201
"Efficacy and Safety of Levofloxacin vs Isoniazid in Latent Tuberculosis Infection in Liver Transplant Patients".
A Phase 3 study testing Levofloxacin and Isoniazid in people with Latent Tuberculosis Infection and Infection in Solid Organ Transplant Recipients, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 18 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Latent Tuberculosis Infection, Infection in Solid Organ Transplant Recipients
- What is being tested?
- Levofloxacin and Isoniazid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 18 sitesSpain
- Study dates
- Jan 2012to Feb 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
Spain18 sites
Complejo Hospitalario Universitario
A Coruña
Complejo Hospitalario de Albacete
Albacete
Hospital Infanta Cristina,
Badajoz
Hospital Clinic
Barcelona
Hospital Vall d'Hebron
Barcelona
Hospital de Cruces
Bilbao
Hospital Reina Sofía
Córdoba
Hospital universitario Virgen de las Nieves
Granada
Hospital 12 de Octubre
Madrid
Hospital Gregorio Marañón
Madrid
Hospital Ramón y Cajal
Madrid
Hospital Universitario Puerta de Hierro
Madrid
Hospital Universitario Carlos Haya
Málaga
Hospital Virgen de la Arrixaca
Murcia
Clínica Universitaria de Navarra
Pamplona
Hospital Marqués de Valdecillas
Santander
Hospital Virgen del Rocío
Seville
Hospital Universitario La Fe
Valencia
About this study
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".
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.
Read the 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.
- Being tested
- Levofloxacin, Isoniazid
- Keywords
- Prophylaxis, Tuberculosis, Transplant recipients, Transplant waiting list
- Medical subject headings
- Latent Tuberculosis, Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevofloxacinDrug
Also called Generic name: Levofloxacin, ATC Code: J01MA., Pharmaceutical form: Levofloxacin 500 mg film-coated tablets
Levofloxacin
IsoniazidDrug
Also called Generic name: Isoniazid., ATC Code: J04AC, Pharmaceutical form: tablets.
300 mg/day for 9 months beginning after transplantation, when the "liver function is stable" and not before 3 months nor after 6 months.
| Study group | Role | What they receive |
|---|---|---|
| levofloxacin | Experimental | Levofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant Receives: Drug: Levofloxacin |
| Isoniazid | Active comparator | 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 Receives: Drug: Isoniazid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months of follow-up
Secondary outcomes (5)
Mortality
Number of deaths of any cause
Measured: 18 months
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.
Measured: During all the 18 months of follow-up
Retransplantation
A new liver transplantation during the follow-up
Measured: 18 months
Graft dysfunction
Development of advanced graft fibrosis stages 3 and 4
Measured: 18 months
Transplant rejection
The occurrence of acute rejection or chronic rejection as per conventional definitions during the follow-up.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2013 (estimated)
- Study startJan 2012
- Primary completionFeb 2014
- Study completionFeb 2014
Why it stopped: Recruitment rythm not sufficent to reach the simple size needed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Latent Tuberculosis InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Collaborators
- Spanish Network for Research in Infectious Diseases
- Responsible party
- Sponsor
- Investigators
- Julián de la Torre Cisneros, MD, Principal investigator, Hospital Universitario Reina Sofía, Córdoba, SpainJosé M. Aguado, MD, PhD, Study chair, Hospital Universitario 12 de Octubre, Madrid
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01761201
- Sponsor's protocol ID
- FLISH-ILT
- Other IDs
- 2010-022302-41
- Acronym
- FLISH-ILT
- Status last verified
- Aug 2014
- First submitted
- 3 Jan 2013
- Last updated
- 6 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, Cervera C, Len O, Carratala J, Cisneros JM, Bou G, Munoz P, Ramos A, Gurgui M, Borrell N, Fortun 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.
PubMed 19445585Aguado JM, Herrero JA, Gavalda J, Torre-Cisneros J, Blanes M, Rufi G, Moreno A, Gurgui 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. doi: 10.1097/00007890-199705150-00015.
PubMed 9158022
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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".
- ClinicalTrials.gov ID
- NCT01761201
- Acronym / sponsor ID
- FLISH-ILT / FLISH-ILT
- Keywords
- Prophylaxis, Tuberculosis, Transplant recipients, Transplant waiting list
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Recruitment rythm not sufficent to reach the simple size needed.
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Collaborators
- Spanish Network for Research in Infectious Diseases
- Study start
- Jan 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 4 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| levofloxacin | Experimental | Drug: LevofloxacinLevofloxacin 500 mg daily for 9 months starting on the waiting list for liver transplant |
| Isoniazid | Active comparator | Drug: IsoniazidIsoniazid 300 mg/day for 9 months beginning after transplantation, when the "liver function is stable" and not before 3 months nor after 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (4 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevofloxacinAlso: Generic name: Levofloxacin, ATC Code: J01MA., Pharmaceutical form: Levofloxacin 500 mg film-coated tabletsLevofloxacin | Drug | levofloxacin |
| IsoniazidAlso: Generic name: Isoniazid., ATC Code: J04AC, Pharmaceutical form: tablets.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 |
Primary outcome
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.
5 secondary outcomes
Mortality
Time frame: 18 months
Toxicity
Time frame: During all the 18 months of follow-up
Retransplantation
Time frame: 18 months
Graft dysfunction
Time frame: 18 months
Transplant rejection
Time frame: 18 months
Results and safety
The study was stopped early (reason given: Recruitment rythm not sufficent to reach the simple size needed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2014.
- Background: PubMed 19445585Torre-Cisneros J, Doblas A, Aguado JM, San Juan R, Blanes M, Montejo M, Cervera C, Len O, Carratala J, Cisneros JM, Bou G, Munoz P, Ramos A, Gurgui M, Borrell N, Fortun 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.
- Background: PubMed 9158022Aguado JM, Herrero JA, Gavalda J, Torre-Cisneros J, Blanes M, Rufi G, Moreno A, Gurgui 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. doi: 10.1097/00007890-199705150-00015.
- official web site for the Spanish Infectious Disease NetworkLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julián de la Torre Cisneros, MD principal investigator
Hospital Universitario Reina Sofía, Córdoba, Spain
José M. Aguado, MD, PhD study chair
Hospital Universitario 12 de Octubre, Madrid
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Levofloxacin and Isoniazid in people with Latent Tuberculosis Infection and Infection in Solid Organ Transplant Recipients, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 18 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Recruitment rythm not sufficent to reach the simple size needed.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in incidence of tuberculosis disease (time frame: 18 months of follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01761201, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2014.