Back to resultsLow-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
Primary Purpose
Fever, Neutropenia, Cancer
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ciprofloxacin and amoxicillin
Outpatient management
i.v. antibiotics
inpatient management
Sponsored by
About this trial
This is an interventional treatment trial for Fever focused on measuring children, oral antibiotics, outpatient treatment, fever and neutropenia
Eligibility 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
Sites / Locations
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital von Hauner
- Pediatric Hematology/Oncology, University Hospital St. Hedwig
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
- Pediatric Hematology/Oncology, Children's Hospital
- Pediatric Hematology/Oncology, University Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard
Experimental
Arm Description
Continued inpatient i.v. antibiotics
Switch to outpatient p.o. antibiotics
Outcomes
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)
Full Information
NCT ID
NCT00107081
First Posted
April 4, 2005
Last Updated
October 29, 2020
Sponsor
Swiss Pediatric Oncology Group
Collaborators
Swiss Cancer League, Bayer, GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT00107081
Brief Title
Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Terminated
Why Stopped
Accrual goal for interventional part not achievable
Study Start Date
January 2004 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
December 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Swiss Pediatric Oncology Group
Collaborators
Swiss Cancer League, Bayer, GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fever, Neutropenia, Cancer
Keywords
children, oral antibiotics, outpatient treatment, fever and neutropenia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard
Arm Type
Active Comparator
Arm Description
Continued inpatient i.v. antibiotics
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Switch to outpatient p.o. antibiotics
Intervention Type
Drug
Intervention Name(s)
ciprofloxacin and amoxicillin
Intervention Type
Procedure
Intervention Name(s)
Outpatient management
Intervention Type
Drug
Intervention Name(s)
i.v. antibiotics
Intervention Type
Procedure
Intervention Name(s)
inpatient management
Primary Outcome Measure Information:
Title
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%)
Title
Efficacy: Response without rehospitalization or changing randomized antibiotics (non-inferiority design, limit 10%)
Secondary Outcome Measure Information:
Title
Improved prediction of low-risk episodes of fever and neutropenia
Title
Description of characteristics of low-risk episodes of fever and neutropenia
Title
Description of characteristics of high-risk episodes of fever and neutropenia (observational study part)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roland A Ammann, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Christoph Aebi, MD
Organizational Affiliation
University Children's Hospital, Bern, Switzerland
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Maja Beck-Popovic, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Lausanne, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eveline SJM de Bont, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Groningen, The Netherlands
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Thomas Kuehne, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Basel, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
David Nadal, MD
Organizational Affiliation
University Children's Hospital, Zurich
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Felix Niggli, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Arne Simon, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Bonn, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Nicole Bodmer, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Hulya Ozsahin, MD
Organizational Affiliation
Pediatric Hematology/Oncology, University Children's Hospital, Geneva, Switzerland
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Bonn
ZIP/Postal Code
D-53113
Country
Germany
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Duesseldorf
ZIP/Postal Code
D-40225
Country
Germany
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Freiburg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital von Hauner
City
Munich
ZIP/Postal Code
D-80337
Country
Germany
Facility Name
Pediatric Hematology/Oncology, University Hospital St. Hedwig
City
Regensburg
ZIP/Postal Code
D-93049
Country
Germany
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Groningen
ZIP/Postal Code
NL-9700
Country
Netherlands
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Basel
ZIP/Postal Code
CH-4005
Country
Switzerland
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Bern
ZIP/Postal Code
CH-3010
Country
Switzerland
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Geneva
ZIP/Postal Code
CH-1205
Country
Switzerland
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Lausanne
ZIP/Postal Code
CH-1011
Country
Switzerland
Facility Name
Pediatric Hematology/Oncology, Children's Hospital
City
Lucerne
ZIP/Postal Code
CH-6004
Country
Switzerland
Facility Name
Pediatric Hematology/Oncology, University Children's Hospital
City
Zurich
ZIP/Postal Code
CH-8032
Country
Switzerland
12. IPD Sharing Statement
Citations:
Citation
Ammann RA. SPOG 2003 FN: Risikobeurteilung und risikoadaptierte Behandlung bei Kindern und Jugendlichen mit Fieber in Neutropenie. Paediatrica 16(1): 28-31, 2005.
Results Reference
background
PubMed Identifier
15747334
Citation
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 Sep;45(3):244-7. doi: 10.1002/pbc.20287. No abstract available.
Results Reference
background
PubMed Identifier
20231680
Citation
Ammann RA, Bodmer N, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kuhne T, Popovic MB, Luthy AR, Aebi C. Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study. J Clin Oncol. 2010 Apr 20;28(12):2008-14. doi: 10.1200/JCO.2009.25.8988. Epub 2010 Mar 15.
Results Reference
result
PubMed Identifier
22271702
Citation
Brack E, Bodmer N, Simon A, Leibundgut K, Kuhne T, Niggli FK, Ammann RA. First-day step-down to oral outpatient treatment versus continued standard treatment in children with cancer and low-risk fever in neutropenia. A randomized controlled trial within the multicenter SPOG 2003 FN study. Pediatr Blood Cancer. 2012 Sep;59(3):423-30. doi: 10.1002/pbc.24076. Epub 2012 Jan 23.
Results Reference
result
PubMed Identifier
21837771
Citation
Luthi F, Leibundgut K, Niggli FK, Nadal D, Aebi C, Bodmer N, Ammann RA. Serious medical complications in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study. Pediatr Blood Cancer. 2012 Jul 15;59(1):90-5. doi: 10.1002/pbc.23277. Epub 2011 Aug 11.
Results Reference
result
PubMed Identifier
21394050
Citation
Agyeman P, Aebi C, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kuhne T, Beck Popovic M, Leibundgut K, Bodmer N, Ammann RA. Predicting bacteremia in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study. Pediatr Infect Dis J. 2011 Jul;30(7):e114-9. doi: 10.1097/INF.0b013e318215a290.
Results Reference
result
PubMed Identifier
25020130
Citation
Ammann RA, Niggli FK, Leibundgut K, Teuffel O, Bodmer N. Exploring the association of hemoglobin level and adverse events in children with cancer presenting with fever in neutropenia. PLoS One. 2014 Jul 14;9(7):e101696. doi: 10.1371/journal.pone.0101696. eCollection 2014.
Results Reference
result
PubMed Identifier
24618935
Citation
Agyeman P, Kontny U, Nadal D, Leibundgut K, Niggli F, Simon A, Kronenberg A, Frei R, Escobar H, Kuhne T, Beck-Popovic M, Bodmer N, Ammann RA. A prospective multicenter study of microbiologically defined infections in pediatric cancer patients with fever and neutropenia: Swiss Pediatric Oncology Group 2003 fever and neutropenia study. Pediatr Infect Dis J. 2014 Sep;33(9):e219-25. doi: 10.1097/INF.0000000000000326.
Results Reference
result
PubMed Identifier
26619462
Citation
Ammann RA, Bodmer N, Simon A, Agyeman P, Leibundgut K, Schlapbach LJ, Niggli FK. Serum Concentrations of Mannan-Binding Lectin (MBL) and MBL-Associated Serine Protease-2 and the Risk of Adverse Events in Pediatric Patients With Cancer and Fever in Neutropenia. J Pediatric Infect Dis Soc. 2013 Jun;2(2):155-61. doi: 10.1093/jpids/pit005. Epub 2013 Feb 13.
Results Reference
result
Links:
URL
http://www.spog.ch
Description
The Swiss Pediatric Oncology Group (SPOG) was the sponsor of this study.
Learn more about this trial
Low-risk Fever and Neutropenia in Children With Cancer: Safety and Efficacy of Oral Antibiotics in an Outpatient Setting
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