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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 26, 2014