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

Fever Clinical Trial

— RR  

Official title:

Prospective Unblinded Randomized Trial to Examine Short vs Prolonged Antibiotic Treatment for Hospitalized Hemato-oncology Patients With Febrile Neutropenia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02463747
• Other study ID #: 0143-15-TLV
• Status: Not yet recruiting
• Phase: Phase 4
• First received: May 26, 2015
• Last updated: June 2, 2015
• Start date: June 2015
• Est. completion date: July 2017

Study information

• Verified date: June 2015
• Source: Tel-Aviv Sourasky Medical Center
• Contact: Ron Ram, MD
• Phone: +972-3-6974138
• Email: ronr[@]tlvmc.gov.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 110
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Febrile Neutropenia
• Fever
• Neutropenia

Intervention

Drug:
• Piperacillin/tazobactam
Initial treatment will be with Piperacillin + Tazobactam
• Ceftazidim
Patient with sensitivity to penicillin will receive Ceftazidim
• Meropenem
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
• Vancomycin
Supplementation of Vancomycin will be at the discretion of the treating physician

Locations

Country	Name	City	State
Israel	Tel-Aviv Sourasky Medicak center / BMT Unit	Tel-Aviv

Sponsors (1)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Interim analysis is planed after 1 year , when a recruitment of 50 patients is expected	Yes
Secondary	Breakthrough fever or Additional bacteremia		5 days after primary treatment	No
Secondary	Clostridium difficile infection		For the duration of hospital stay - an expected average of 4 weeks	No
Secondary	Survival		During 30 days from begining of treatment	No
Secondary	Duration of Hospitalization		For the duration of hospital stay - an expected average of 4 weeks	Yes
Secondary	Number of days of Neutropenia		For the duration of hospital stay - an expected average of 4 weeks	Yes
Secondary	Any systemic organ Failure (Renal / Hepatic / Cardio or pulmonary)		For the duration of hospital stay - an expected average of 4 weeks	Yes

External Links

•   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
•   Paul M, Soares-Weiser K, Grozinsky S, Leibovici L. Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropaenia. Cochrane Database Syst Rev. 2003
•   Rolston KV. Challenges in the treatment of infections caused by gram-positive and gram-negative bacteria in patients with cancer and neutropenia. Clin. Infect Dis. 2005;40 Suppl 4:S246
•   Sepkowitz KA. Treatment of patients with hematologic neoplasm, fever, and neutropenia. Clin Infect Dis. 2005 Apr 1;40 Suppl 4:S253-6.
•   Shiu J, Wang E, Tejani AM, Wasdell M. Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections. Cochrane Database Syst Rev. 2013 Mar 28;3:CD008481. doi: 10.1002/14651858.CD008481.pub2.
•   Teo J, Liew Y, Lee W, Kwa AL. Prolonged infusion versus intermittent boluses of ß-lactam antibiotics for treatment of acute infections: a meta-analysis. Int J Antimicrob Agents. 2014 May;43(5):403-11. doi: 10.1016/j.ijantimicag.2014.01.027. Epub 2014
•   Thomas P. Lodise, Pharm.D., Ben M. Lomaestro, Pharm.D., and George L. Drusano, M.D. Application of Antimicrobial Pharmacodynamic Concepts into Clinical Practice: Focus on b-Lactam Antibiotics, Insights from the Society of Infectious Diseases Pharmacist
•   Viscoli C, Varnier O, Machetti M. Infections in patients with febrile neutropenia: epidemiology, microbiology, and risk stratification. Clin Infect Dis. 2005;40 Suppl 4:S240.
•   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]
•   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