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

Swiss Pediatric Oncology Group

Status and phase: Terminated; Phase 3

Conditions: Fever; Neutropenia; Cancer

Treatments: Drug: i.v. antibiotics; Drug: ciprofloxacin and amoxicillin; Procedure: Outpatient management; Procedure: inpatient management

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00107081

OCS - 01466-02-2004

Umbrella Network Trial 2004.3

SPOG 2003 FN

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 70 patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 2 patient groups

Standard

Active Comparator group

Description:

Continued inpatient i.v. antibiotics

Treatment:

Drug: i.v. antibiotics

Procedure: inpatient management

Experimental

Experimental group

Description:

Switch to outpatient p.o. antibiotics

Treatment:

Procedure: Outpatient management

Drug: ciprofloxacin and amoxicillin