Clinical trial NCT02463747: Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
Official title: Prospective Unblinded Randomized Trial to Examine Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Fever
Febrile Neutropenia
Keywords: Neutropenic fever
extended infusion
beta-lactam
empiric antibiotic treatment
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2015-06-04
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

1. Tazocin: 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. - 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:

1. The fever does not decrease after 24 hours
2. The patient is not hemodynamically stable or developes an organ failure
3. Evolving of sensitivity response (allergy) suspected to be a response to antibiotic patient is treated with.
4. 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.

Eligibility criteria: 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.

Primary outcomes:
measure: A successful response to treatment
timeFrame: Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected
Secondary outcomes:
measure: Breakthrough fever or Additional bacteremia
timeFrame: 5 days after primary treatment
measure: Clostridium difficile infection
timeFrame: For the duration of hospital stay - an expected average of 4 weeks
measure: Survival
timeFrame: During 30 days from begining of treatment
measure: Duration of Hospitalization
timeFrame: For the duration of hospital stay - an expected average of 4 weeks
measure: Number of days of Neutropenia
timeFrame: For the duration of hospital stay - an expected average of 4 weeks
measure: Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)
timeFrame: For the duration of hospital stay - an expected average of 4 weeks
Other outcomes:
Locations:
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medicak center / BMT Unit
Study officials:
affiliation: Head of BMt Unit / hematology division
name: Dr. Ron Ram, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.