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Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia (RR)

Primary Purpose

Fever, Febrile Neutropenia

Status
Unknown status
Phase
Phase 4
Locations
Israel
Study Type
Interventional
Intervention
Piperacillin/tazobactam
Ceftazidim
Meropenem
Vancomycin
Sponsored by
Tel-Aviv Sourasky Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fever focused on measuring Neutropenic fever, extended infusion, beta-lactam, empiric antibiotic treatment

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Patients who are able to sign an informed consent form
  2. Hospitalized patients for one of the following reasons:

    • Induction or consolidation for Acute Leukemia
    • Patients Hospitalized for Autologous BMT
    • Patients Hospitalized for Allogeneic BMT.

Exclusion Criteria:

  1. Patients under the age of 18.
  2. Patients who are unable to provide informed consent.
  3. Patients with acute lymphatic leukemia hospitalized for maintenance treatment
  4. Patients who will not be staying for the entire duration of neutropenia in house.

Sites / Locations

  • Tel-Aviv Sourasky Medicak center / BMT Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Prolonged Infusion of antibiotics

Fixed time infusion of antibiotics

Arm Description

Prolonged (4 hours) Infusion of antibiotics. Intervention: Primary care would be one of three options: Piperacillin/tazobactam : 4.5gr, TID, I.V. Or Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician.

Fixed time (half and hour) infusion of antibiotics. Intervention: Primary care would be one of three options: Piperacillin/tazobactam : 4.5gr, TID, I.V. Or Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician/

Outcomes

Primary Outcome Measures

A successful response to treatment
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.

Secondary Outcome Measures

Breakthrough fever or Additional bacteremia
Clostridium difficile infection
Survival
Duration of Hospitalization
Number of days of Neutropenia
Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)

Full Information

First Posted
May 26, 2015
Last Updated
June 2, 2015
Sponsor
Tel-Aviv Sourasky Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02463747
Brief Title
Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
Acronym
RR
Official Title
Prospective Unblinded Randomized Trial to Examine Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Unknown status
Study Start Date
June 2015 (undefined)
Primary Completion Date
June 2017 (Anticipated)
Study Completion Date
July 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tel-Aviv Sourasky Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fever, Febrile Neutropenia
Keywords
Neutropenic fever, extended infusion, beta-lactam, empiric antibiotic treatment

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
110 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Prolonged Infusion of antibiotics
Arm Type
Experimental
Arm Description
Prolonged (4 hours) Infusion of antibiotics. Intervention: Primary care would be one of three options: Piperacillin/tazobactam : 4.5gr, TID, I.V. Or Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician.
Arm Title
Fixed time infusion of antibiotics
Arm Type
Active Comparator
Arm Description
Fixed time (half and hour) infusion of antibiotics. Intervention: Primary care would be one of three options: Piperacillin/tazobactam : 4.5gr, TID, I.V. Or Fortum (Ceftazidim): 2.0gr, TID, I.V. - for penicillin-sensitive patients. Or Meropenem: 1.0gr, TID, I.V. Supplementation of Vancomycin will be at the discretion of the treating physician/
Intervention Type
Drug
Intervention Name(s)
Piperacillin/tazobactam
Other Intervention Name(s)
Tazocin
Intervention Description
Initial treatment will be with Piperacillin + Tazobactam
Intervention Type
Drug
Intervention Name(s)
Ceftazidim
Other Intervention Name(s)
Fortum
Intervention Description
Patient with sensitivity to penicillin will receive Ceftazidim
Intervention Type
Drug
Intervention Name(s)
Meropenem
Other Intervention Name(s)
Ceftazidim
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Vancomycin
Other Intervention Name(s)
Non
Intervention Description
Supplementation of Vancomycin will be at the discretion of the treating physician
Primary Outcome Measure Information:
Title
A successful response to treatment
Description
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.
Time Frame
Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected
Secondary Outcome Measure Information:
Title
Breakthrough fever or Additional bacteremia
Time Frame
5 days after primary treatment
Title
Clostridium difficile infection
Time Frame
For the duration of hospital stay - an expected average of 4 weeks
Title
Survival
Time Frame
During 30 days from begining of treatment
Title
Duration of Hospitalization
Time Frame
For the duration of hospital stay - an expected average of 4 weeks
Title
Number of days of Neutropenia
Time Frame
For the duration of hospital stay - an expected average of 4 weeks
Title
Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)
Time Frame
For the duration of hospital stay - an expected average of 4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ron Ram, MD
Phone
+972-3-6974138
Email
ronr@tlvmc.gov.il
First Name & Middle Initial & Last Name or Official Title & Degree
Ronen Ben-Ami, MD
Phone
+972-3-6974347
Email
ronenba@tlvmc.gov.il
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Ron Ram, MD
Organizational Affiliation
Head of BMt Unit / hematology division
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tel-Aviv Sourasky Medicak center / BMT Unit
City
Tel-Aviv
ZIP/Postal Code
6423906
Country
Israel
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ron Ram, MD
Phone
+972-3-6974138
Email
ronr@tlvmc.gov.il
First Name & Middle Initial & Last Name & Degree
Shachar Porat, B.Sc.
Phone
+972-3-6972428
Email
shacharp@tlvmc.gov.il

12. IPD Sharing Statement

Citations:
PubMed Identifier
29608680
Citation
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. Erratum In: Clin Infect Dis. 2018 Sep 14;67(7):1151.
Results Reference
derived
Links:
URL
http://cid.oxfordjournals.org/content/52/4/e56.long
Description
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases soci
URL
http://cid.oxfordjournals.org/content/36/9/1103.long
Description
Wisplinghoff H, Seifert H, Wenzel RP, Edmond MB. Current trends in the epidemiology of nosocomial bloodstream infections in patients with hematological malignancies and solid neoplasms in hospitals in the United States. Clin Infect Dis. 2003;36(9):1103
URL
http://cid.oxfordjournals.org/content/26/1/1.long
Description
W.A. Craig. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis, 26 (1998), pp. 1-10 [quiz 11-2]

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Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia

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