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

This study has been terminated.
(Accrual goal for interventional part not achievable)
Sponsor:
Collaborators:
Swiss Cancer League
Bayer
Information provided by:
Swiss Pediatric Oncology Group
ClinicalTrials.gov Identifier:
NCT00107081
First received: April 4, 2005
Last updated: August 31, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Fever
Neutropenia
Cancer
Drug: ciprofloxacin and amoxicillin
Procedure: Outpatient management
Drug: i.v. antibiotics
Procedure: inpatient management
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Swiss Pediatric Oncology Group:

Primary Outcome Measures:
  • 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:
  • 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)

Enrollment: 70
Study Start Date: January 2004
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard
Continued inpatient i.v. antibiotics
Drug: i.v. antibiotics Procedure: inpatient management
Experimental: Experimental
Switch to outpatient p.o. antibiotics
Drug: ciprofloxacin and amoxicillin Procedure: Outpatient management

Detailed 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.
  Eligibility

Ages Eligible for Study:   1 Year to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00107081

Locations
Germany
Pediatric Hematology/Oncology, University Children's Hospital
Bonn, Germany, D-53113
Pediatric Hematology/Oncology, University Children's Hospital
Duesseldorf, Germany, D-40225
Pediatric Hematology/Oncology, University Children's Hospital
Freiburg, Germany, D-79106
Pediatric Hematology/Oncology, University Children's Hospital von Hauner
Munich, Germany, D-80337
Pediatric Hematology/Oncology, University Hospital St. Hedwig
Regensburg, Germany, D-93049
Netherlands
Pediatric Hematology/Oncology, University Children's Hospital
Groningen, Netherlands, NL-9700
Switzerland
Pediatric Hematology/Oncology, University Children's Hospital
Basel, Switzerland, CH-4005
Pediatric Hematology/Oncology, University Children's Hospital
Bern, Switzerland, CH-3010
Pediatric Hematology/Oncology, University Children's Hospital
Geneva, Switzerland, CH-1205
Pediatric Hematology/Oncology, University Children's Hospital
Lausanne, Switzerland, CH-1011
Pediatric Hematology/Oncology, Children's Hospital
Lucerne, Switzerland, CH-6004
Pediatric Hematology/Oncology, University Children's Hospital
Zurich, Switzerland, CH-8032
Sponsors and Collaborators
Swiss Pediatric Oncology Group
Swiss Cancer League
Bayer
Investigators
Study Chair: Roland A Ammann, MD Pediatric Hematology/Oncology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland
Study Director: Christoph Aebi, MD University Children's Hospital, Bern, Switzerland
Principal Investigator: Maja Beck-Popovic, MD Pediatric Hematology/Oncology, University Children's Hospital, Lausanne, Switzerland
Principal Investigator: Eveline SJM de Bont, MD Pediatric Hematology/Oncology, University Children's Hospital, Groningen, The Netherlands
Principal Investigator: Thomas Kuehne, MD Pediatric Hematology/Oncology, University Children's Hospital, Basel, Switzerland
Study Director: David Nadal, MD University Children's Hospital, Zurich, Switzerland
Principal Investigator: Felix Niggli, MD Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland
Principal Investigator: Arne Simon, MD Pediatric Hematology/Oncology, University Children's Hospital, Bonn, Germany
Study Director: Nicole Bodmer, MD Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland
Principal Investigator: Hulya Ozsahin, MD Pediatric Hematology/Oncology, University Children's Hospital, Geneva, Switzerland
  More Information

Additional Information:
Publications:

Responsible Party: Swiss Pediatric Oncology Group; Roland A Ammann, MD
ClinicalTrials.gov Identifier: NCT00107081     History of Changes
Other Study ID Numbers: SPOG 2003 FN, Umbrella Network Trial 2004.3, OCS - 01466-02-2004
Study First Received: April 4, 2005
Last Updated: August 31, 2012
Health Authority: Switzerland: Swissmedic
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Swiss Pediatric Oncology Group:
children
oral antibiotics
outpatient treatment
fever and neutropenia

Additional relevant MeSH terms:
Fever
Neutropenia
Body Temperature Changes
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Amoxicillin
Anti-Bacterial Agents
Ciprofloxacin
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014