PreventionPhase 3NCT02981615
Phase 3 Multicenter Randomized Double Blind Placebo Controlled Study With Antibacterial Prophylaxis in Azacitidine Treated MDS Patients
A Phase 3 study testing Levofloxacin in people with Prevention, run by Sheba Medical Center at 1 site in Israel.
Trial summary
Infections are a major and prevalent life-threatening complication among patients with myelodysplastic syndrome (MDS). Currently, the role of prophylactic antibacterial agents after chemotherapy in MDS patients remains controversial and there are no clinical guidelines for infection prophylaxis in this clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Prevention
- What is being tested?
- Levofloxacin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Aug 2017to 30 Jul 2022
- 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
- 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.
Who cannot join
- 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.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Infections are a major and prevalent life-threatening complication among patients with myelodysplastic syndrome (MDS). Currently, the role of prophylactic antibacterial agents after chemotherapy in MDS patients remains controversial and there are no clinical guidelines for infection prophylaxis in this clinical setting. We will conduct a prospective study to evaluate the potential benefit of prophylactic antibacterial (Levofloxacin) on the rate of febrile episodes/infections in Azacytidine treated MDS patients.
Read the detailed description
This is a national, multicenter, phase III, randomized, parallel arms, double blind, placebo controlled clinical trial to evaluate the efficacy and safety of antibacterial prophylaxis - Levofloxacin 500mg/d given p.o.in newly diagnosed MDS patients who are more than 18 years of age and fulfil an indication for Azacytidine treatment. Patients will be treated for up to 4 cycles of Levofloxacin, or placebo. 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. Subject allocated to the placebo arm will be treated with placebo once a day, starting on day 10 from beginning of each cycle until day 28. Levofloxacin and placebo treatment will be continued in the first 4 Azacytidine cycles. This study consists of 3 periods for each study subject: pre-treatment period, treatment period and follow up period. Expected duration of subject participation is 6 months Pre-treatment period: Assessments: MDS evaluation by bone marrow examination including cytogenetics/ FISH must be performed within half a year of the first dose of study drug.
- Conditions
- Prevention
- Being tested
- Levofloxacin, Placebo Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevofloxacinDrug
Also called levo, tavanic
one tablet (500mg) a day, from day 10 to day 28 in every cycle of the 4 first cycles
Placebo Oral TabletDrug
one tablet a day, from day 10 to day 28 in every cycle of the 4 first cycles
| Study group | Role | What they receive |
|---|---|---|
| treatment arm | Experimental | 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. Receives: Drug: Levofloxacin |
| placebo | Placebo comparator | 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. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Febrile episodes (fever >38.0c) rate.
Measured: from study entry to 6 months later
Secondary outcomes (11)
Time to first febrile episode
Measured: from study entry to 6 months later
Clinically-documented (CDI) or microbiologically documented infections rate (MDI)
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
Measured: from study entry to 6 months later
Bacteremia rate
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.
Measured: from study entry to 6 months later
Invasive fungal infections rate, as defined by the EORTC/MSG consensus group
Measured: from study entry to 6 months later
Number of participants use of antibacterial therapy other than levofloxain prophylaxis.
Measured: from study entry to 6 months later
Episodes of diarrhea rate
Measured: from study entry to 6 months later
C. difficile infection rate
Measured: from study entry to 6 months later
MDIs or bacteremia caused by quinolone-resistant bacteria rate
Measured: from study entry to 6 months later
Hospitalization for infection rate.
Measured: from study entry to 6 months later
Six months overall survival rate.
Measured: from study entry to 6 months later
QOL as measured by the FACT An questioner.
Measured: from study entry to 6 months later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2016 (estimated)
- Study start1 Aug 2017
- Primary completion30 Jul 2022
- Study completion30 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PreventionStudies 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Dr. Drorit Merkel, Sheba Medical Center
- Investigators
- Drorit G Merkel, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02981615
- Sponsor's protocol ID
- 1680-14-SMC
- Status last verified
- Nov 2023
- First submitted
- 28 Nov 2016
- Last updated
- 27 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT02981615
- Acronym / sponsor ID
- 1680-14-SMC
- Conditions
- Prevention
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Study start
- 1 Aug 2017 (actual)
- Primary completion
- 30 Jul 2022 (actual)
- Study completion
- 30 Jul 2022 (actual)
- First posted
- 5 Dec 2016 (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.
Infections are a major and prevalent life-threatening complication among patients with myelodysplastic syndrome (MDS). Currently, the role of prophylactic antibacterial agents after chemotherapy in MDS patients remains controversial and there are no clinical guidelines for infection prophylaxis in this clinical setting. We will conduct a prospective study to evaluate the potential benefit of prophylactic antibacterial (Levofloxacin) on the rate of febrile episodes/infections in Azacytidine treated MDS patients.
Detailed description
This is a national, multicenter, phase III, randomized, parallel arms, double blind, placebo controlled clinical trial to evaluate the efficacy and safety of antibacterial prophylaxis - Levofloxacin 500mg/d given p.o.in newly diagnosed MDS patients who are more than 18 years of age and fulfil an indication for Azacytidine treatment. Patients will be treated for up to 4 cycles of Levofloxacin, or placebo. 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. Subject allocated to the placebo arm will be treated with placebo once a day, starting on day 10 from beginning of each cycle until day 28. Levofloxacin and placebo treatment will be continued in the first 4 Azacytidine cycles. This study consists of 3 periods for each study subject: pre-treatment period, treatment period and follow up period. Expected duration of subject participation is 6 months Pre-treatment period: Assessments: MDS evaluation by bone marrow examination including cytogenetics/ FISH must be performed within half a year of the first dose of study drug.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| treatment arm | Experimental | Drug: LevofloxacinSubjects 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. |
| placebo | Placebo comparator | Drug: Placebo Oral TabletSubject 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (3 listed)
- 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.
- -
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: levo, tavanicone tablet (500mg) a day, from day 10 to day 28 in every cycle of the 4 first cycles | Drug | treatment arm |
| Placebo Oral Tabletone tablet a day, from day 10 to day 28 in every cycle of the 4 first cycles | Drug | placebo |
Primary outcome
Febrile episodes (fever >38.0c) rate.
Time frame: from study entry to 6 months later
11 secondary outcomes
Time to first febrile episode
Time frame: from study entry to 6 months later
Clinically-documented (CDI) or microbiologically documented infections rate (MDI)
Time frame: from study entry to 6 months later
Bacteremia rate
Time frame: from study entry to 6 months later
Invasive fungal infections rate, as defined by the EORTC/MSG consensus group
Time frame: from study entry to 6 months later
Number of participants use of antibacterial therapy other than levofloxain prophylaxis.
Time frame: from study entry to 6 months later
Episodes of diarrhea rate
Time frame: from study entry to 6 months later
C. difficile infection rate
Time frame: from study entry to 6 months later
MDIs or bacteremia caused by quinolone-resistant bacteria rate
Time frame: from study entry to 6 months later
Hospitalization for infection rate.
Time frame: from study entry to 6 months later
Six months overall survival rate.
Time frame: from study entry to 6 months later
QOL as measured by the FACT An questioner.
Time frame: from study entry to 6 months later
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Drorit G Merkel, MD principal investigator
Sheba Medical Center
1 site 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 in people with Prevention, run by Sheba Medical Center at 1 site in Israel.
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 3 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: finished, as of the sponsor's last update on 27 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Febrile episodes (fever >38.0c) rate. (time frame: from study entry to 6 months later). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Nov 2023.