Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting

Study Overview
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Brief Summary
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The purpose of this study is to determine whether, in children with cancer presenting with fever in severe chemotherapy-induced neutropenia at low risk for medical complications, oral antibiotics in an outpatient setting after an initial phase of intravenous antibiotics and in-hospital observation for 8 to 22 hours, is not inferior as to safety and efficacy compared to continued intravenous antibiotics given in-hospital.

Detailed Description
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Details on antimicrobial therapy At presentation with FN (fever and neutropenia) and during an initial inpatient observation period of 8 to 22 hours, empirical intravenous broad-spectrum antibiotics are given. Type and dosage are chosen by the treating physician. Patients randomized to continued intravenous antibiotics continue with these antibiotics. Patients randomized to oral antibiotics receive a combination of oral ciprofloxacin (25 to 30 mg/kg/day, top dose 1500 mg/day) plus oral amoxicillin (65 to 80 mg/kg/day, top dose 2250 mg/day), both given in two doses per day. In both groups, the study gives guidelines (for certain situations) and rules (for other situations) when to change and when to stop antibiotics. Details on clinical and laboratory controls During antibiotic therapy, patients are seen daily, either as inpatients or as outpatients according to randomization. Complete blood counts are performed at least every second day. After stopping antibiotic therapy and until resolution of severe neutropenia (if applicable), patients are seen every other day, with a complete blood count. Patients randomized to outpatient management have the possibility to contact at any time of the day (and night) a pediatric oncologist in case of problems, in order to discuss necessity for emergency control and/or rehospitalization.

Official Title
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A Prospective Multi-Center Study on Pediatric Patients With Fever in Severe Chemotherapy Induced Neutropenia, Including a Randomized Comparison of Outpatient Management and Oral Antimicrobial Therapy Versus Inpatient Management and Intravenous Antimicrobial Therapy in a Subgroup With Low Risk of Adverse Events (Low-Risk Subgroup Study)

Conditions
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Fever, Neutropenia, Cancer

Intervention / Treatment
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* Drug: ciprofloxacin and amoxicillin
* Procedure: Outpatient management
* Drug: i.v. antibiotics
* Procedure: inpatient management


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chemotherapy because of malignancy Severe neutropenia (absolute neutrophil count ≤ 0.5x10E9/L) Fever (axillary temperature ≥ 38.5°C once or ≥ 38.0°C during ≥ 2 hours) Able to swallow oral medication Written informed consent from patients and/or parents Exclusion Criteria: Status post myeloablative chemotherapy Diagnosis: acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or B-cell Non-Hodgkin lymphoma Bone marrow involvement by malignancy ≥ 25% Any comorbidity requiring hospitalization: [1] mean arterial blood pressure < 50 mmHg (up to 10 years) / < 60 mmHg (older than 10 years); [2] oxygen saturation < 94% at room air; [3] radiologically defined pneumonia; [4] focal bacterial infection; [5] blood cultures taken at presentation reported positive at reassessment; [6] need for inpatient treatment or observation due to any other reason, as judged by the physician in charge Ever shaking chills Ever axillary temperature ≥ 39.5°C Antibacterial treatment before presentation with fever and neutropenia (except for prevention against Pneumocystis jiroveci [formerly P. carinii] pneumonia) Modification or de novo institution of a prophylaxis against P. jiroveci pneumonia Modification or de novo institution of a therapy with G-CSF or GM-CSF. Allergy to ciprofloxacin and/or amoxicillin Serum creatinine level above the upper limit of normal range

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard<br>Continued inpatient i.v. antibiotics | Drug: i.v. antibiotics<br> <br> Procedure: inpatient management<br> <br> |
| Experimental: Experimental<br>Switch to outpatient p.o. antibiotics | Drug: ciprofloxacin and amoxicillin<br> <br> Procedure: Outpatient management<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: No serious medical complication due to infection (death, treatment in ICU [Intensive Care Unit], potentially life-threatening complication) (non-inferiority-design, limit 3.5%) |  |  | 
| Efficacy: Response without rehospitalization or changing randomized antibiotics (non-inferiority design, limit 10%) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved prediction of low-risk episodes of fever and neutropenia |  |  | 
| Description of characteristics of low-risk episodes of fever and neutropenia |  |  | 
| Description of characteristics of high-risk episodes of fever and neutropenia (observational study part) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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children, oral antibiotics, outpatient treatment, fever and neutropenia