Neutropenia, FebrilePhase 4CEF-10NCT05061654
CEFtolozane-Tazobactam for the Empiric Anti-bacterial Treatment of Neutropenic Fever in Hematology Patients
A Phase 4 study testing Ceftolozane-tazobactam IV in people with Neutropenia, Febrile and Hematologic Cancer, run by Hamad Medical Corporation at 1 site in Qatar.
Trial summary
Patients with blood cancers and those who received a bone marrow transplant frequently have low circulating white blood cell countS. Fever in patients with low white blood cell count requires early appropriate antibiotic treatment to prevent complications including death. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neutropenia, Febrile, Hematologic Cancer
- What is being tested?
- Ceftolozane-tazobactam IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteQatar
- Study dates
- Aug 2022to Jun 2024
- Phase
- Phase 4
- 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
- Hospitalized with an underlying diagnosis of hematological cancer or receipt of hematopoietic stem cell transplantation.
- Age ≥18 years.
- Absolute neutrophil count (ANC) of <0.5x10^9/L or <1.0x10^9/L with a predicted decline to <0.5x10^9/L within the next 2 days.
- Oral temperature of ≥ 38.3 °C once, ≥ 38.0 °C lasting for at least 1 hour, or ≥ 38.0 °C twice within 12 hours.
Who cannot join
- Allergy to cephalosporins.
- Expected survival of ≤72 hours.
- Expected ANC recovery within ≤72 hours.
- Receipt of any antipseudomonal carbapenem therapy within the preceding 14 days.
- Documented current or past infection or colonization with ceftolozane-tazobactam- resistant Enterobacterales or P. aeruginosa.
- Pregnancy.
- Previous enrollment in CEF-10 Study (subjects previously enrolled in this study cannot be enrolled again during subsequent episodes of neutropenic fever).
- Ongoing therapy or planned continuation of therapy outside the National Center for Cancer Care and Research.
Trial locations and contacts
1 site in 1 country.
Qatar1 site
Hamad Medical Corporation, National Center for Cancer Care and Research
Doha
About this study
Official title: CEFtolozane-Tazobactam for the Empiric Anti-bacterial Treatment of Neutropenic Fever in Hematology Patients; a Single-arm, Single-center, Open-label Clinical Trial (CEF-10 Study)
Patients with blood cancers and those who received a bone marrow transplant frequently have low circulating white blood cell countS. Fever in patients with low white blood cell count requires early appropriate antibiotic treatment to prevent complications including death. Bacteria have increasingly become more resistant to existing antibiotic options. Ceftolozane-tazobactam is a newer type of antibiotic that has been shown to be safe and effective in infections caused by several types of resistant bacteria that can cause serious infections in individuals with low blood count. This study aims to examine the effectiveness of this antibiotic in these types of patients.
Patients with blood cancer and those who have received a bone transplant will be offered the option to join this study if they develop unexplained fever. If informed consent is granted, they will receive ceftolozane-tazobactam on top of the usual care that such patients receive. The patients will then be followed very closely to check their response to the treatment and if they develop any untoward events. The study will include 164 patients over an estimated 2 year period.
The study is funded by Merck \& Co, the company that manufactures the study antibiotic. However, Merck \& Co. will not be involved in the actual running of the study, the collection of the study results or their analysis and interpretation. The study protocol has been reviewed and approved by an independent research oversight committee.
Read the detailed description
The role of early appropriate empiric anti-bacterial therapy in reducing morbidity and mortality in patients with prolonged neutropenia has long being documented. The National Center for Cancer Care and Research (NCCCR) antibiograms for recent years showed increasing rates of ESBL-producing E. coli and K. pneumoniae, as well as reduced susceptibility of P. aeruginosa isolates to piperacillin-tazobactam. Ceftolozane-tazobactam is a newer β-lactam-β-lactamase inhibitor combination with a broad in-vitro spectrum that includes ESBL and AmpC-producing Enterobacterales, as well as multidrug resistant P. aeruginosa. The clinical efficacy and safety of ceftolozane-tazobactam was demonstrated in registrational randomized clinical trials in multiple settings. However, clinical experience with ceftolozane-tazobactam in patients with hematological malignancy or HSCT is very limited. The aim of this study is to explore the potential role of ceftolozane-tazobactam as empiric treatment for hematology patients with neutropenic fever of unknown origin.
The primary objective is to assess the efficacy of ceftolozane-tazobactam as empiric anti-bacterial therapy for neutropenic fever in patients with hematological malignancy or HSCT.
The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study. Patients admitted to NCCCR with a malignant hematological diagnosis and/or HSCT will be screened daily for possible inclusion in the study. Participants will receive empiric therapy with ceftolozane-tazobactam intravenously. All remaining care will be consistent with standard clinical care for patients with neutropenic fever. The Primary endpoint will be treatment success at 72 hours of ceftolozane-tazobactam therapy without modification of anti-bacterial therapy. Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis).
The study will be conducted in full conformance with principles of the "Declaration of Helsinki", Good Clinical Practice (GCP), and within the laws and regulations of Ministry of Public Health in Qatar. Participation will be subject to written informed consent. The study is sponsored by Hamad Medical Corporation. Funding and medication supply is provided by Merck \& Co (MSD) through its Investigator Initiated Studies Program. MSD will not have any role in data collection, data analysis or driving study conclusions.
- Conditions
- Neutropenia, Febrile, Hematologic Cancer
- Being tested
- Ceftolozane-tazobactam IV
- Medical subject headings
- Febrile Neutropenia, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftolozane-tazobactam IVDrug
Also called Zerbaxa
Empiric Ceftolozane-tazobactam IV 3g over 1 hour every 8 hours. The dose will be reduced to 1.5g 8 hourly in patients with CrCl of 30-50 ml/min, and to 750mg every 8 hours in those with CrCl of 15-29 ml/min. Patients on hemodialysis will receive 2.25g loading dose followed by 450mg every 8 hours.
| Study group | Role | What they receive |
|---|---|---|
| Treatment arm | Experimental | Eligible patients will be started on empiric ceftolozane-tazobactam in addition to standard care. Receives: Drug: Ceftolozane-tazobactam IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment success without modification of anti-bacterial therapy
Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis).
Measured: 72 hours
Secondary outcomes (3)
Treatment success without modification of anti-bacterial therapy
Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis)
Measured: 7 days
Days to defervescence
Counted from the first oral temperature of <38oC which is sustained for ≥48 hours
Measured: 30 days
30-day survival
Survival for 30 days from initiation of therapy
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2021
- Study startAug 2022 (estimated)
- Primary completionJan 2024 (estimated)
- Study completionJun 2024 (estimated)
Why it stopped: Administrative constraints
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neutropenia, FebrileStudies of the same condition, open and under way.
- More trials run by Hamad Medical CorporationThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hamad Medical Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Ali S. Omrani, FRCP, Principal investigator, Hamad Medical Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05061654
- Sponsor's protocol ID
- MRC-02-21-015
- Acronym
- CEF-10
- Status last verified
- Sep 2021
- First submitted
- 20 Sep 2021
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CEFtolozane-Tazobactam for the Empiric Anti-bacterial Treatment of Neutropenic Fever in Hematology Patients; a Single-arm, Single-center, Open-label Clinical Trial (CEF-10 Study)
- ClinicalTrials.gov ID
- NCT05061654
- Acronym / sponsor ID
- CEF-10 / MRC-02-21-015
- Conditions
- Neutropenia, Febrile, Hematologic Cancer
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative constraints
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Hamad Medical CorporationIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Aug 2022 (estimated)
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Jun 2024 (estimated)
- First posted
- 29 Sep 2021 (actual)
- 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.
Patients with blood cancers and those who received a bone marrow transplant frequently have low circulating white blood cell countS. Fever in patients with low white blood cell count requires early appropriate antibiotic treatment to prevent complications including death. Bacteria have increasingly become more resistant to existing antibiotic options. Ceftolozane-tazobactam is a newer type of antibiotic that has been shown to be safe and effective in infections caused by several types of resistant bacteria that can cause serious infections in individuals with low blood count. This study aims to examine the effectiveness of this antibiotic in these types of patients.
Patients with blood cancer and those who have received a bone transplant will be offered the option to join this study if they develop unexplained fever. If informed consent is granted, they will receive ceftolozane-tazobactam on top of the usual care that such patients receive. The patients will then be followed very closely to check their response to the treatment and if they develop any untoward events. The study will include 164 patients over an estimated 2 year period.
The study is funded by Merck \& Co, the company that manufactures the study antibiotic. However, Merck \& Co. will not be involved in the actual running of the study, the collection of the study results or their analysis and interpretation. The study protocol has been reviewed and approved by an independent research oversight committee.
Detailed description
The role of early appropriate empiric anti-bacterial therapy in reducing morbidity and mortality in patients with prolonged neutropenia has long being documented. The National Center for Cancer Care and Research (NCCCR) antibiograms for recent years showed increasing rates of ESBL-producing E. coli and K. pneumoniae, as well as reduced susceptibility of P. aeruginosa isolates to piperacillin-tazobactam. Ceftolozane-tazobactam is a newer β-lactam-β-lactamase inhibitor combination with a broad in-vitro spectrum that includes ESBL and AmpC-producing Enterobacterales, as well as multidrug resistant P. aeruginosa. The clinical efficacy and safety of ceftolozane-tazobactam was demonstrated in registrational randomized clinical trials in multiple settings. However, clinical experience with ceftolozane-tazobactam in patients with hematological malignancy or HSCT is very limited. The aim of this study is to explore the potential role of ceftolozane-tazobactam as empiric treatment for hematology patients with neutropenic fever of unknown origin.
The primary objective is to assess the efficacy of ceftolozane-tazobactam as empiric anti-bacterial therapy for neutropenic fever in patients with hematological malignancy or HSCT.
The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study. Patients admitted to NCCCR with a malignant hematological diagnosis and/or HSCT will be screened daily for possible inclusion in the study. Participants will receive empiric therapy with ceftolozane-tazobactam intravenously. All remaining care will be consistent with standard clinical care for patients with neutropenic fever. The Primary endpoint will be treatment success at 72 hours of ceftolozane-tazobactam therapy without modification of anti-bacterial therapy. Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis).
The study will be conducted in full conformance with principles of the "Declaration of Helsinki", Good Clinical Practice (GCP), and within the laws and regulations of Ministry of Public Health in Qatar. Participation will be subject to written informed consent. The study is sponsored by Hamad Medical Corporation. Funding and medication supply is provided by Merck \& Co (MSD) through its Investigator Initiated Studies Program. MSD will not have any role in data collection, data analysis or driving study conclusions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study will be a prospective, non-comparative, single-arm, single center, open-label interventional study.
| Arm | Type | Receives |
|---|---|---|
| Treatment arm | Experimental | Drug: Ceftolozane-tazobactam IVEligible patients will be started on empiric ceftolozane-tazobactam in addition to standard care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Hospitalized with an underlying diagnosis of hematological cancer or receipt of hematopoietic stem cell transplantation.
- Age ≥18 years.
- Absolute neutrophil count (ANC) of <0.5x10^9/L or <1.0x10^9/L with a predicted decline to <0.5x10^9/L within the next 2 days.
- Oral temperature of ≥ 38.3 °C once, ≥ 38.0 °C lasting for at least 1 hour, or ≥ 38.0 °C twice within 12 hours.
Key exclusion criteria (8 listed)
- Allergy to cephalosporins.
- Expected survival of ≤72 hours.
- Expected ANC recovery within ≤72 hours.
- Receipt of any antipseudomonal carbapenem therapy within the preceding 14 days.
- Documented current or past infection or colonization with ceftolozane-tazobactam- resistant Enterobacterales or P. aeruginosa.
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 |
|---|---|---|
| Ceftolozane-tazobactam IVAlso: ZerbaxaEmpiric Ceftolozane-tazobactam IV 3g over 1 hour every 8 hours. The dose will be reduced to 1.5g 8 hourly in patients with CrCl of 30-50 ml/min, and to 750mg every 8 hours in those with CrCl of 15-29 ml/min. Patients on hemodialysis will receive 2.25g loading dose followed by 450mg every 8 hours. | Drug | Treatment arm |
Primary outcome
Treatment success without modification of anti-bacterial therapy
Time frame: 72 hours
Treatment success is defined as a composite of defervescence, resolution of any baseline clinical signs of infection, microbiological eradication of any baseline bacterial pathogen, and no modification of anti-bacterial therapy by addition of or switch to an agent with microbiological activity against Enterobacterales or P. aeruginosa (except the addition of sulfamethoxazole-trimethoprim for P. jiroveci prophylaxis).
3 secondary outcomes
Treatment success without modification of anti-bacterial therapy
Time frame: 7 days
Days to defervescence
Time frame: 30 days
30-day survival
Time frame: 30 days
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 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.
Ali S. Omrani, FRCP principal investigator
Hamad Medical Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ceftolozane-tazobactam IV in people with Neutropenia, Febrile and Hematologic Cancer, run by Hamad Medical Corporation at 1 site in Qatar.
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 4 inclusion and 8 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: withdrawn, as of the sponsor's last update on 14 Aug 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 Qatar. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 withdrawn before enrolling participants, so there are no results.
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?
Treatment success without modification of anti-bacterial therapy (time frame: 72 hours). 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 14 Aug 2023.