Low-Risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting - Full Text View

Sponsor:	Swiss Pediatric Oncology Group
Collaborators:	Swiss Cancer League Bayer
Information provided by:	Swiss Pediatric Oncology Group
ClinicalTrials.gov Identifier:	NCT00107081

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	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Antibiotics Cancer Fever

Drug Information available for: Amoxicillin Amoxicillin sodium Amoxicillin trihydrate Ciprofloxacin Ciprofloxacin hydrochloride Ciprofloxacin lactate

U.S. FDA Resources

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)

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 Hospital St. Hedwig
Regensburg, Germany, D-93049
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
Netherlands
Pediatric Hematology/Oncology, University Children's Hospital
Groningen, Netherlands, NL-9700
Switzerland
Pediatric Hematology/Oncology, University Children's Hospital
Zurich, Switzerland, CH-8032
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
Basel, Switzerland, CH-4005

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:

The Swiss Institute for Applied Cancer Research (SIAK) is the umbrella organization of patient-oriented cancer research in Switzerland. The Swiss Pediatric Oncology Group (SPOG) is one of its three member organizations. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications:

Ammann RA, Simon A, de Bont ES. Low risk episodes of fever and neutropenia in pediatric oncology: Is outpatient oral antibiotic therapy the new gold standard of care? Pediatr Blood Cancer. 2005 Mar 3; [Epub ahead of print] No abstract available.

Responsible Party:	Swiss Pediatric Oncology Group; Roland A Ammann, MD
Study ID Numbers:	SPOG 2003 FN, Umbrella Network Trial 2004.3, OCS - 01466-02-2004
Study First Received:	April 4, 2005
Last Updated:	January 12, 2008
ClinicalTrials.gov Identifier:	NCT00107081 History of Changes
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:

Anti-Infective Agents
Amoxicillin
Molecular Mechanisms of Pharmacological Action
Hematologic Diseases
Agranulocytosis
Enzyme Inhibitors
Leukocyte Disorders
Body Temperature Changes
Pharmacologic Actions

Fever
Neutropenia
Signs and Symptoms
Anti-Bacterial Agents
Ciprofloxacin
Therapeutic Uses
Leukopenia
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 08, 2010