FeverPhase 4RRNCT02463747
Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
A Phase 4 study testing Piperacillin/tazobactam, Ceftazidim and Meropenem in people with Fever and Febrile Neutropenia, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
Neutropenic fever is a life threatening condition that is not rare in patients suffering from hematologic disorders, and of paramount importance to early and effective treatment. In this trial we concentrate on hospitalized patients with hematologic malignancies who develop neutropenic fever. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Fever, Febrile Neutropenia
- What is being tested?
- Piperacillin/tazobactam, Ceftazidim and Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2015to Jul 2017
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who are able to sign an informed consent form
- Hospitalized patients for one of the following reasons:
- Induction or consolidation for Acute Leukemia
- Patients Hospitalized for Autologous BMT
- Patients Hospitalized for Allogeneic BMT.
Who cannot join
- Patients under the age of 18.
- Patients who are unable to provide informed consent.
- Patients with acute lymphatic leukemia hospitalized for maintenance treatment
- Patients who will not be staying for the entire duration of neutropenia in house.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Tel-Aviv Sourasky Medicak center / BMT Unit
Tel Aviv, 6423906
Ron Ram, MD, +972-3-6974138, ronr@tlvmc.gov.il
Shachar Porat, B.Sc., +972-3-6972428, shacharp@tlvmc.gov.il
About this study
Official title: Prospective Unblinded Randomized Trial to Examine Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
Neutropenic fever is a life threatening condition that is not rare in patients suffering from hematologic disorders, and of paramount importance to early and effective treatment. In this trial we concentrate on hospitalized patients with hematologic malignancies who develop neutropenic fever.
In recent years, several studies were conducted to examine possible changes in the conventional empirical treatment, assuming that administration of the antibiotics in a prolonged infusion would allow for a greater fT > MIC that will lead to a better efficacy.
Read more
These studies were carried out in different populations and there is only limited information about the importance of continuous infusion therapy in patients with hematologic diseases with neutropenic fever.
Research goals: The main goal is to compare between two groups of hematologic patients with neutropenic fever, The first group will receive antibiotic therapy in extended infusion, and the second (control) group will receive the treatment in a fixed time.
Read the detailed description
METHODS: Each patient who will be hospitalized in the Department of Bone Marrow Transplantation and which meets the Inclusion criteria for, will be offered to participate in the study. If fever appears during hospitalization empirical treatment of neutropenia will be initiated performed in accordance with the allocation of the patient in the study. Therapeutic success is defined as a combination of several clinical parameters, including: a decline in Fever, the recurrence of fever and improvement in infection.
METHODS: Study format - Prospective unblinded randomized trial.
Neutropenic fever measurement will be set above the fold of 38.3 ° C or fever over 38.0 ° C lasting more than an hour. Neutropenia is defined as absolute neutrophil count (ANC) less than 500 cells / mm3, or expected to fall below this value for the next 48 hours.
Primary care would be one of three options:
- Tazocin: 4.5gr, TID, I.V. Or
- Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or
- Meropenem: 1.0gr, TID, I.V. - In cases of hypotension not responding to fluids resuscitation, and in consultation with the infectious diseases unit - we will start empirical treatment with Meropenem.
Supplementation of Vancomycin will be at the discretion of the treating physician.
Antibiotic therapy will be replaced, in coordination with the Department of Infectious Diseases in the following cases:
- The fever does not decrease after 24 hours
- The patient is not hemodynamically stable or developes an organ failure
- Evolving of sensitivity response (allergy) suspected to be a response to antibiotic patient is treated with.
- sensitivity response was received from the laboratory culture Bacteriologist demanding a change in antibiotics.
Replacement of antibiotic therapy is defined as a failure as defined by the primary endpoint. In such a case, continued treatment of the patient would be according to the BMT unit protocol for treatment for neutropenic fever.
- Conditions
- Fever, Febrile Neutropenia
- Being tested
- Piperacillin/tazobactam, Ceftazidim, Meropenem, Vancomycin
- Keywords
- Neutropenic fever, extended infusion, beta-lactam, empiric antibiotic treatment
- Medical subject headings
- Fever, Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin/tazobactamDrug
Also called Tazocin
Initial treatment will be with Piperacillin + Tazobactam
CeftazidimDrug
Also called Fortum
Patient with sensitivity to penicillin will receive Ceftazidim
MeropenemDrug
Also called Ceftazidim
In cases of hypotension that do not respond to fluids resuscitation , and in consultation with the infectious diseases unit - we will start empirical treatment with Meropenem
VancomycinDrug
Also called Non
Supplementation of Vancomycin will be at the discretion of the treating physician
| Study group | Role | What they receive |
|---|---|---|
| Prolonged Infusion of antibiotics | Experimental | Prolonged (4 hours) Infusion of antibiotics.
Intervention:
Primary care would be one of three options:
1. Piperacillin/tazobactam : 4.5gr, TID, I.V.
Or
2. Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients.
Or
3. Meropenem: 1.0gr, TID, I.V.
Supplementation of Vancomycin will be at the discretion of the treating physician. Receives: Drug: Piperacillin/tazobactam; Drug: Ceftazidim; Drug: Meropenem; Drug: Vancomycin |
| Fixed time infusion of antibiotics | Active comparator | Fixed time (half and hour) infusion of antibiotics.
Intervention:
Primary care would be one of three options:
1. Piperacillin/tazobactam : 4.5gr, TID, I.V.
Or
2. Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients.
Or
3. Meropenem: 1.0gr, TID, I.V.
Supplementation of Vancomycin will be at the discretion of the treating physician/ Receives: Drug: Piperacillin/tazobactam; Drug: Ceftazidim; Drug: Meropenem; Drug: Vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
A successful response to treatment
A successful response to treatment will be defined by a combination of all the following:
- A defervescence of fever for at least 48 hours. B. Disappearance or improvement of clinical signs and symptoms of infection.
- No: bacteremia / re-emergence of fever / signs of infection within 5 days from starting of treatment.
Measured: Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected
Secondary outcomes (6)
Breakthrough fever or Additional bacteremia
Measured: 5 days after primary treatment
Clostridium difficile infection
Measured: For the duration of hospital stay - an expected average of 4 weeks
Survival
Measured: During 30 days from begining of treatment
Duration of Hospitalization
Measured: For the duration of hospital stay - an expected average of 4 weeks
Number of days of Neutropenia
Measured: For the duration of hospital stay - an expected average of 4 weeks
Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)
Measured: For the duration of hospital stay - an expected average of 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionJun 2017 (estimated)
- Study completionJul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FeverStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 110 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, michal roll, Tel-Aviv Sourasky Medical Center
- Investigators
- Dr. Ron Ram, MD, Principal investigator, Head of BMt Unit / hematology division
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02463747
- Sponsor's protocol ID
- 0143-15-TLV
- Acronym
- RR
- Status last verified
- Jun 2015
- First submitted
- 26 May 2015
- Last updated
- 4 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Ram R, Halavy Y, Amit O, Paran Y, Katchman E, Yachini B, Kor S, Avivi I, Ben-Ami R. Extended vs Bolus Infusion of Broad-Spectrum beta-Lactams for Febrile Neutropenia: An Unblinded, Randomized Trial. Clin Infect Dis. 2018 Sep 28;67(8):1153-1160. doi: 10.1093/cid/ciy258.
PubMed 29608680
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Unblinded Randomized Trial to Examine Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
- ClinicalTrials.gov ID
- NCT02463747
- Acronym / sponsor ID
- RR / 0143-15-TLV
- Conditions
- Fever, Febrile Neutropenia
- Keywords
- Neutropenic fever, extended infusion, beta-lactam, empiric antibiotic treatment
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 110 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Study start
- Jun 2015
- Primary completion
- Jun 2017 (estimated)
- Study completion
- Jul 2017 (estimated)
- First posted
- 4 Jun 2015 (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.
Neutropenic fever is a life threatening condition that is not rare in patients suffering from hematologic disorders, and of paramount importance to early and effective treatment. In this trial we concentrate on hospitalized patients with hematologic malignancies who develop neutropenic fever.
In recent years, several studies were conducted to examine possible changes in the conventional empirical treatment, assuming that administration of the antibiotics in a prolonged infusion would allow for a greater fT > MIC that will lead to a better efficacy.
These studies were carried out in different populations and there is only limited information about the importance of continuous infusion therapy in patients with hematologic diseases with neutropenic fever.
Research goals: The main goal is to compare between two groups of hematologic patients with neutropenic fever, The first group will receive antibiotic therapy in extended infusion, and the second (control) group will receive the treatment in a fixed time.
Detailed description
METHODS: Each patient who will be hospitalized in the Department of Bone Marrow Transplantation and which meets the Inclusion criteria for, will be offered to participate in the study. If fever appears during hospitalization empirical treatment of neutropenia will be initiated performed in accordance with the allocation of the patient in the study. Therapeutic success is defined as a combination of several clinical parameters, including: a decline in Fever, the recurrence of fever and improvement in infection.
METHODS: Study format - Prospective unblinded randomized trial.
Neutropenic fever measurement will be set above the fold of 38.3 ° C or fever over 38.0 ° C lasting more than an hour. Neutropenia is defined as absolute neutrophil count (ANC) less than 500 cells / mm3, or expected to fall below this value for the next 48 hours.
Primary care would be one of three options:
- Tazocin: 4.5gr, TID, I.V. Or
- Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or
- Meropenem: 1.0gr, TID, I.V. - In cases of hypotension not responding to fluids resuscitation, and in consultation with the infectious diseases unit - we will start empirical treatment with Meropenem.
Supplementation of Vancomycin will be at the discretion of the treating physician.
Antibiotic therapy will be replaced, in coordination with the Department of Infectious Diseases in the following cases:
- The fever does not decrease after 24 hours
- The patient is not hemodynamically stable or developes an organ failure
- Evolving of sensitivity response (allergy) suspected to be a response to antibiotic patient is treated with.
- sensitivity response was received from the laboratory culture Bacteriologist demanding a change in antibiotics.
Replacement of antibiotic therapy is defined as a failure as defined by the primary endpoint. In such a case, continued treatment of the patient would be according to the BMT unit protocol for treatment for neutropenic fever.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prolonged Infusion of antibiotics | Experimental | Drug: Piperacillin/tazobactam, Drug: Ceftazidim, Drug: Meropenem, Drug: VancomycinProlonged (4 hours) Infusion of antibiotics. Intervention: Primary care would be one of three options: 1. Piperacillin/tazobactam : 4.5gr, TID, I.V. Or 2. Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or 3. Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician. |
| Fixed time infusion of antibiotics | Active comparator | Drug: Piperacillin/tazobactam, Drug: Ceftazidim, Drug: Meropenem, Drug: VancomycinFixed time (half and hour) infusion of antibiotics. Intervention: Primary care would be one of three options: 1. Piperacillin/tazobactam : 4.5gr, TID, I.V. Or 2. Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or 3. Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician/ |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients who are able to sign an informed consent form
- Hospitalized patients for one of the following reasons:
Key exclusion criteria (4 listed)
- Patients under the age of 18.
- Patients who are unable to provide informed consent.
- Patients with acute lymphatic leukemia hospitalized for maintenance treatment
- Patients who will not be staying for the entire duration of neutropenia in house.
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 |
|---|---|---|
| Piperacillin/tazobactamAlso: TazocinInitial treatment will be with Piperacillin + Tazobactam | Drug | Fixed time infusion of antibiotics, Prolonged Infusion of antibiotics |
| CeftazidimAlso: FortumPatient with sensitivity to penicillin will receive Ceftazidim | Drug | Fixed time infusion of antibiotics, Prolonged Infusion of antibiotics |
| MeropenemAlso: CeftazidimIn cases of hypotension that do not respond to fluids resuscitation , and in consultation with the infectious diseases unit - we will start empirical treatment with Meropenem | Drug | Fixed time infusion of antibiotics, Prolonged Infusion of antibiotics |
| VancomycinAlso: NonSupplementation of Vancomycin will be at the discretion of the treating physician | Drug | Fixed time infusion of antibiotics, Prolonged Infusion of antibiotics |
Primary outcome
A successful response to treatment
Time frame: Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected
A successful response to treatment will be defined by a combination of all the following: A. A defervescence of fever for at least 48 hours. B. Disappearance or improvement of clinical signs and symptoms of infection. C. No: bacteremia / re-emergence of fever / signs of infection within 5 days from starting of treatment.
6 secondary outcomes
Breakthrough fever or Additional bacteremia
Time frame: 5 days after primary treatment
Clostridium difficile infection
Time frame: For the duration of hospital stay - an expected average of 4 weeks
Survival
Time frame: During 30 days from begining of treatment
Duration of Hospitalization
Time frame: For the duration of hospital stay - an expected average of 4 weeks
Number of days of Neutropenia
Time frame: For the duration of hospital stay - an expected average of 4 weeks
Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)
Time frame: For the duration of hospital stay - an expected average of 4 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2015.
- Derived from this study: PubMed 29608680Ram R, Halavy Y, Amit O, Paran Y, Katchman E, Yachini B, Kor S, Avivi I, Ben-Ami R. Extended vs Bolus Infusion of Broad-Spectrum beta-Lactams for Febrile Neutropenia: An Unblinded, Randomized Trial. Clin Infect Dis. 2018 Sep 28;67(8):1153-1160. doi: 10.1093/cid/ciy258.
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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.
Dr. Ron Ram, MD principal investigator
Head of BMt Unit / hematology division
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 Piperacillin/tazobactam, Ceftazidim and Meropenem in people with Fever and Febrile Neutropenia, run by Tel-Aviv Sourasky 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 5 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: status not confirmed, as of the sponsor's last update on 4 Jun 2015. 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ron Ram, MD (+972-3-6974138, ronr@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A successful response to treatment (time frame: Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected). 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 NCT02463747, which also lists 1 linked publication.
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 4 Jun 2015.