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

This study is currently recruiting patients.

Sponsors and Collaborators: Swiss Pediatric Oncology Group
Swiss Cancer League
Bayer Corporation
Information provided by: Swiss Pediatric Oncology Group

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 Treatment or Intervention Phase
Fever
Neutropenia
Cancer
 Drug: ciprofloxacin and amoxicillin
 Procedure: Outpatient management
Phase III

MedlinePlus related topics:  Blood and Blood Disorders;   Cancer;   Cancer Alternative Therapy;   Fever

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)

Further Study Details: 
Primary Outcomes: 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 Outcomes: 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)
Expected Total Enrollment:  360

Study start: January 2004;  Expected completion: June 2009
Last follow-up: December 2008;  Data entry closure: March 2009

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   -   18 Years,  Genders Eligible for Study:  Both

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

Location and Contact Information

Roland A Ammann, MD      0041 31 632 93 72    roland.ammann@insel.ch
Andrea Zaugg, RN      0041 31 632 93 72    spog.2003.fn@insel.ch

Germany
      Pediatric Hematology/Oncology, University Children's Hospital, Bonn,  D-53113,  Germany; Recruiting
Arne Simon, MD  0049 228 28 73 254    arne.simon@ukb.uni-bonn.de 
Arne Simon, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital, Duesseldorf,  D-40225,  Germany; Not yet recruiting
Hans-Jurgen Laws, MD  0049 211 81 16 185    Laws@med.uni-duesseldorf.de 
Hans-Jurgen Laws, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital, Freiburg,  D-79106,  Germany; Not yet recruiting
Udo Kontny, MD  0049 761 270 44 67    kontny@kikli.ukl.uni-freiburg.de 
Udo Kontny, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital von Hauner, Munich,  D-80337,  Germany; Recruiting
Monika Streiter, MD  0049 89 51 60 28 11    Monika.Streiter@med.uni-muenchen.de 
Monika Streiter, MD,  Principal Investigator

Netherlands
      Pediatric Hematology/Oncology, University Children's Hospital, Groningen,  NL-9700,  Netherlands; Not yet recruiting
Eveline SJM de Bont, MD  0031 50 36 14 213    e.s.j.m.de.bont@bkk.azg.nl 
Eveline SJM de Bont, MD,  Principal Investigator

Switzerland
      Pediatric Hematology/Oncology, University Children's Hospital, Basel,  CH-4005,  Switzerland; Recruiting
Thomas Kuehne, MD  0041 61 685 65 65    thomas.kuehne@ukbb.ch 
Thomas Kuehne, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital, Bern,  CH-3010,  Switzerland; Recruiting
Roland A Ammann, MD  0041 31 632 93 72    roland.ammann@insel.ch 
Andrea Zaugg, RN  0041 31 632 93 72    spog.2003.fn@insel.ch 
Roland A Ammann, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital, Geneva,  CH-1205,  Switzerland; Not yet recruiting

      Pediatric Hematology/Oncology, University Children's Hospital, Lausanne,  CH-1011,  Switzerland; Not yet recruiting
Maja Beck-Popovic, MD  0041 21 314 35 67    Maja.Beck-Popovic@chuv.hospvd.ch 
Maja Beck-Popovic, MD,  Principal Investigator

      Pediatric Hematology/Oncology, Children's Hospital, Lucerne,  CH-6004,  Switzerland; Not yet recruiting
Ueli Caflisch, MD  0041 41 205 11 11    ueli.caflisch@ksl.ch 
Ueli Caflisch, MD,  Principal Investigator

      Pediatric Hematology/Oncology, Children's Hospital, St. Gallen,  CH-9006,  Switzerland; Not yet recruiting
Hugo Ubieto, MD  0041 71 243 71 11    hugo.ubieto@gd-kispi.sg.ch 
Hugo Ubieto, MD,  Principal Investigator

      Pediatric Hematology/Oncology, University Children's Hospital, Zurich,  CH-8032,  Switzerland; Recruiting
Nicole Bodmer, MD  0041 1 266 71 11    nicole.bodmer@kispi.unizh.ch 
Felix Niggli, MD,  Principal Investigator
Nicole Bodmer, MD,  Sub-Investigator

Study chairs or principal investigators

Roland A Ammann, MD,  Study Chair,  Pediatric Hematology/Oncology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland   
Christoph Aebi, MD,  Study Director,  University Children's Hospital, Bern, Switzerland   
Maja Beck-Popovic, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Lausanne, Switzerland   
Eveline SJM de Bont, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Groningen, The Netherlands   
Thomas Kuehne, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Basel, Switzerland   
David Nadal, MD,  Study Director,  University Children's Hospital, Zurich, Switzerland   
Felix Niggli, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland   
Annette Ridolfi Luethy, MD,  Study Director,  Pediatric Hematology/Oncology, University Children's Hospital, Bern, Switzerland   
Arne Simon, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Bonn, Germany   

More Information

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.

Study ID Numbers:  SPOG 2003 FN; Umbrella Network Trial 2004.3; OCS - 01466-02-2004
Record last reviewed:  April 2005
Last Updated:  April 7, 2005
Record first received:  April 4, 2005
ClinicalTrials.gov Identifier:  NCT00107081
Health Authority: Switzerland: Swissmedic (Awaiting confirmation); Germany: Federal Institute for Drugs and Medicinal Devices (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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