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Short Versus Extended Antibiotic Treatment With a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients With FUO

Information source: VU University Medical Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Febrile Neutropenia; Hematological Malignancy

Intervention: Discontinuation of imipenem-cilastatin or meropenem (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: VU University Medical Center

Official(s) and/or principal investigator(s):
Jeroen JWM Janssen, MD, PhD, Principal Investigator, Affiliation: VU University Medical Center
Michiel A van Agtmael, MD, PhD, Principal Investigator, Affiliation: VU University Medical Center
Mark MH Kramer, Prof., MD, Study Chair, Affiliation: VU University Medical Center
Sonja Zweegman, Prof.,MD, Study Chair, Affiliation: VU University Medical Center

Overall contact:
Nick A de Jonge, MD, Phone: +31(0)204444334, Email: short@vumc.nl

Summary

A multicenter open-label non-inferiority randomized clinical trial comparing the safety (non-inferiority) of short antibiotic treatment (72 hours) with an anti-pseudomonal carbapenem with regard to treatment failure in comparison with extended treatment (at least 9 days) of high-risk febrile neutropenia in hematology patients receiving standard antimicrobial prophylaxis.

Clinical Details

Official title: Short Versus Extended Antibiotic Treatment With a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients With Fever of Unknown Origin: a Randomized Multicenter Non-inferiority Trial.

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: The percentage of patients with failed treatment

Secondary outcome:

All-cause mortality.

Infection-related mortality.

The length of hospitalization in days.

Treatment strategy failure

The total number of febrile episodes during neutropenia.

Time to defervescence

Incidence and prevalence of Clostridium difficile infection

Candida spp. colonization in (surveillance) cultures

Cost of antimicrobial therapy per admission

The percentage of patients with a MASCC-score≥21 and treatment failure (defined as in primary endpoint)

The percentage of patients with mucositis and positive blood cultures or short treatment failure.

Bacterial resistance in blood cultures and surveillance cultures (including minimal inhibitory concentrations (MIC)).

The incidence and prevalence of fungal, viral, or carbapenem-resistant (inherent/acquired) infections until the end of neutropenia

Detailed description: Episodes of fever are very common in patients undergoing intensive chemotherapy treatment for malignant hematological disease. More than 80% of patients experience one or more episodes of fever after their first cycle of chemotherapy. Only 20-30% of these patients have a clinically documented focus and mostly include infections of skin, intestinal tract and lung, while at most 10-25% of these patients have microbiologically proven bacteremia during these episodes. Patients with malignant hematological diseases and intensive chemotherapy induced neutropenia are extremely prone to overwhelming bacterial infections. Therefore, empirical antibiotic treatment is initiated at the first occurrence of fever, even if no apparent cause for the fever is evident. Most protocols advice treatment with very broad-spectrum antibiotics, mostly anti-pseudomonal carbapenems or fourth generation anti-pseudomonal cephalosporins. Prolonged continuation of treatment may induce bacterial resistance. In view of the possible emergence of bacterial resistance due to prolonged antibiotic administration, continuation until recovery of neutropenia is suboptimal because it is costly because of longer hospital admissions, higher antibiotics costs and more possible adverse reactions. Recent observational data (Slobbe et al) has showed that in adult hematological patients with febrile neutropenia, discontinuation of empiric antibacterial therapy after three days can be safe if no infectious etiology can be found, even in cases with persistent fever. However no RCT has hitherto been performed to support this observational data. This study compares the safety (non-inferiority) of short treatment (72 hours) versus extended treatment (at least 9 days) with an anti-pseudomonal carbapenem for hematology patients with unexplained high risk febrile neutropenia. We hypothesize that a more restrictive use of broad-spectrum antibiotic use of three days in unexplained fever in neutropenic hematology patients is non-inferior to the present extended use during at least 9 days which would lead to a more restrictive use of antibiotics and less multiresistant strains of bacteria, costs and hospitalization length in the future.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Patients with malignant hematological diseases being treated with cytotoxic chemotherapy or stem cell transplantation; 2. High-risk neutropenia (Absolute neutrophil count (ANC) <0. 5x109/L which is expected to last longer than 7 days); 3. Fever (One single measured tympanic membrane temperature of >38. 5°C or a temperature of >38. 0°C during 2 subsequent measurements separated by at least 2 hours); 4. Age 18 years or older; 5. Written informed consent. Exclusion Criteria: 1. Contraindications to use of imipenem-cilastatin or meropenem such as allergy, previous severe side-effects or previous microbiological cultures with carbapenem-resistant microorganism(s). 2. Corticosteroid use ≥10 mg per day prednisolone or equivalent during the previous 7 days. 3. Clinically or microbiologically documented infection. 4. Symptoms of septic shock (systolic blood pressure <90 mm Hg unresponsive to fluid resuscitation and/or oliguria (urine production <500mL/day). 5. Previous enrollment in this study during the same episode of neutropenia. 6. Any critical illness for which Intensive Care Unit treatment is required. 7. Legal incompetency

Locations and Contacts

Nick A de Jonge, MD, Phone: +31(0)204444334, Email: short@vumc.nl

VU university medical center, Amsterdam 1081 HV, Netherlands; Not yet recruiting
Nick A de Jonge, MD, Phone: +31(0)20-444334, Email: short@vumc.nl
Jeroen JWM Janssen, MD, PhD, Principal Investigator
Michiel A van Agtmael, MD, PhD, Principal Investigator
Nick A de Jonge, MD, Sub-Investigator
Jonne J Sikkens, MD, Sub-Investigator
Additional Information

Trial website

Starting date: December 2014
Last updated: November 13, 2014

Page last updated: August 23, 2015

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