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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02149329
• Date of registration: 19/05/2014
• Prospective Registration: Yes
• Primary sponsor: VU University Medical Center
• Public title: Short Versus Extended Antibiotic Treatment With a Carbapenem for High-risk Febrile Neutropenia in Hematology Patients With FUO SHORT
• Scientific 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.
• Date of first enrolment: December 2014
• Target sample size: 276
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02149329
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Netherlands

Contacts

• Name: Michiel A van Agtmael, MD, PhD
• Affiliation: VU University Medical Center

• Name: Sonja Zweegman, Prof.,MD
• Affiliation: VU University Medical Center

• Name: Jeroen JWM Janssen, MD, PhD
• Affiliation: VU University Medical Center

• Name: Mark MH Kramer, Prof., MD
• Affiliation: VU University Medical Center

Key inclusion & exclusion 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 for more than 3
consecutive day 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Febrile Neutropenia

Hematological Malignancy

Intervention(s)

Drug: Discontinuation of imipenem-cilastatin or meropenem

Primary Outcome(s)

Death/ARDS or Septic shock [Time Frame: From randomization until the end of neutropenia (neutrophil count >=0.5x10e9/L) up to 6 months after randomization.]

The percentage of patients with failed treatment [Time Frame: Between randomization (at 3x24 hours) and before 9x24hours after treatment initiation)]

Secondary Outcome(s)

All-cause mortality. [Time Frame: 1. From 3x24hours of treatment until the end of neutropenia. 2. Within 30 days after the end of neutropenia]

Treatment strategy failure [Time Frame: after 3x24hours of treatment with a carbapenem and until the end of the neutropenic episode]

Late treatment failure [Time Frame: Between 9x24hours and 14x24hours after onset of treatment with a carbapemen.]

The incidence and prevalence of fungal, viral, or carbapenem-resistant (inherent/acquired) infections until the end of neutropenia [Time Frame: om the onset of fever until the end of the neutropenic episode, with an estimated average of 21 days.]

The percentage of patients with mucositis and positive blood cultures or short treatment failure. [Time Frame: From onset of fever until 30 days after end of neutropenia.]

Infection-related mortality. [Time Frame: 1. From 3x24hours of treatment until the end of neutropenia. 2.Within 30 days after recovery of neutropenia]

The total number of febrile episodes during neutropenia. [Time Frame: From the start of neutropenia (ANC<0.5x10^9) until the end of neutropenia, an expected average of 21 days]

Cost of antimicrobial therapy per admission [Time Frame: From admission until discharge, with an estimated average of 4 weeks]

The length of hospitalization in days. [Time Frame: From admission until discharge, with an estimated average of 4 weeks]

The percentage of patients with a MASCC-score=21 and treatment failure (defined as in primary endpoint) [Time Frame: From the onset of fever until the end of the neutropenic episode, with an estimated average of 21 days.]

Bacterial resistance in blood cultures and surveillance cultures (including minimal inhibitory concentrations (MIC)). [Time Frame: All previous cultures and cultures performed until 30 days after the end of neutropenia.]

Candida spp. colonization in (surveillance) cultures [Time Frame: From onset of fever until 30 days after the end of neutropenia.]

Incidence and prevalence of Clostridium difficile infection [Time Frame: Onset of fever until 30 days after the end of neutropenia.]

Time to defervescence [Time Frame: Onset of fever until defervenscence, an expected average of 5 days.]

Secondary ID(s)

2014-001546-25

2000735

NL48960.029.14

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

FondsNutsOhra

ZonMw: The Netherlands Organisation for Health Research and Development