- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02981615
Phase 3 Multicenter Randomized Double Blind Placebo Controlled Study With Antibacterial Prophylaxis in Azacitidine Treated MDS Patients
A Phase 3, Multicenter, Randomized, Double Blind, Placebo Controlled Study to Assess the Safety and Efficacy of Antibacterial Prophylaxis for Prevention of Infections in Azacitidine Treated Myelodysplastic Syndrome Patients.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Drorit G Merkel, MD
- Phone Number: 972526669168
- Email: drorit.merkel@sheba.health.gov.il
Study Contact Backup
- Name: Yshai Ofran, MD
- Phone Number: 972-50-2061524
- Email: y_ofran@rambam.health.gov.il
Study Locations
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-
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Tel Hashomer, Israel, 52621
- Chim Sheba Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age > 18 years at the time of signing the informed consent document.
- Have a documented diagnosis of primary or secondary MDS according to WHO 2008 classification (appendix I), fulfilling an indication for Azacytidine treatment.
- Females of childbearing potential (FCBP) may participate, providing they meet the following conditions: Agree to use at least two effective contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study, and for 3 months following the last dose of study drug; and have a negative serum or urine pregnancy test (investigator's discretion; sensitivity at least 25 mIU/mL) at screening; and have a negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study therapy in the treatment phase (note that the screening serum pregnancy test can be used as the test prior to starting study therapy in treatment phase if it is performed within the 72-hour time frame).
- Male subjects with a female partner of childbearing potential must agree to the use of at least two physician-approved contraceptive methods throughout the course of the study and should avoid fathering a child during the course of the study and for 3 months following the last dose of study drug.
- Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
- Able to adhere to the study visit schedule and other protocol requirements.
Exclusion Criteria:
Prior treatment with any of the following:
1.1. Azacitidine (any formulation), decitabine or other hypomethylating agent 1.2. Lenalidomide 2. Prior allogeneic or autologous stem cell transplant 3. Use of hydroxyurea within 7 days prior to randomization. 4. Diagnosis of AML (i.e. >30% blasts in bone marrow). 5. Ongoing adverse events from previous treatment, regardless of the time period. 6. Systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment) 7. Known Human Immunodeficiency Virus (HIV) 8. Known or suspected hypersensitivity to azacitidine or mannitol. 9. Known or suspected hypersensitivity to Levofloxacin. 10. Pregnant or lactating females. 11. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study. 12. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. 13. Participation to an investigational drug trial in the last month before randomization.
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Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: treatment arm
Subjects allocated to the treatment arm of the study will be administrated Levofloxacin 500mg/d given p.o. once a day, starting on day 10 from beginning of each cycle until day 28 on an ambulatory basis.
Levofloxacin will be continued in the first 4 Azacytidine cycles.
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one tablet (500mg) a day, from day 10 to day 28 in every cycle of the 4 first cycles
Other Names:
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Placebo Comparator: placebo
Subject allocated to the placebo arm will be treated with placebo once a day, starting on day 10 from beginning until day 28 of each of the first 4 cycles.
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one tablet a day, from day 10 to day 28 in every cycle of the 4 first cycles
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Febrile episodes (fever >38.0c) rate.
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to first febrile episode
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
|
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Clinically-documented (CDI) or microbiologically documented infections rate (MDI)
Time Frame: from study entry to 6 months later
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Clinically-documented (CDI) or microbiologically documented infections (MDI) other than bacteremia, defined as sepsis inflammatory response syndrome (SIRS) associated with local inflammation (e.g.
pneumonia, UTI, abdominal infection) with or without microbiological documentation from the site of infection, excluding episodes accompanied by bacteremia.
Virologically documented infections will not be included as MDIs
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from study entry to 6 months later
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Bacteremia rate
Time Frame: from study entry to 6 months later
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Bacteremia, defined SIRS accompanied by growth of a bloodstream isolate in one or more blood culture.
Growth of typical skin commensals (coagulase-negative Staphylococci, diphtheroids) will require growth from at least two separate sets of blood cultures.
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from study entry to 6 months later
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Invasive fungal infections rate, as defined by the EORTC/MSG consensus group
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Number of participants use of antibacterial therapy other than levofloxain prophylaxis.
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Episodes of diarrhea rate
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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C. difficile infection rate
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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MDIs or bacteremia caused by quinolone-resistant bacteria rate
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Hospitalization for infection rate.
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Six months overall survival rate.
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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QOL as measured by the FACT An questioner.
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Correlation between serum ferritin level (> 1000ng/ml) as a predictor of the infection rate
Time Frame: from study entry to 4months later
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from study entry to 4months later
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Correlation between serum ferritin level (> 1000ng/ml) as a predictor of mortality rate
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Correlation of antibiotic prophylaxis use versus placebo on the rate of infections
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Correlation of antibiotic prophylaxis use versus placebo on the mortality rate
Time Frame: from study entry to 6 months later
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from study entry to 6 months later
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Drorit G Merkel, MD, Sheba Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1680-14-SMC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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