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

NCT ID: NCT00107081

Last Updated: 2020-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2007-12-31

Brief Summary

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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

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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.

Conditions

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Fever Neutropenia Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard

Continued inpatient i.v. antibiotics

Group Type ACTIVE_COMPARATOR

i.v. antibiotics

Intervention Type DRUG

inpatient management

Intervention Type PROCEDURE

Experimental

Switch to outpatient p.o. antibiotics

Group Type EXPERIMENTAL

ciprofloxacin and amoxicillin

Intervention Type DRUG

Outpatient management

Intervention Type PROCEDURE

Interventions

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ciprofloxacin and amoxicillin

Intervention Type DRUG

Outpatient management

Intervention Type PROCEDURE

i.v. antibiotics

Intervention Type DRUG

inpatient management

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Swiss Cancer League

OTHER

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

Swiss Pediatric Oncology Group

OTHER

Sponsor Role lead

Responsible Party

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Swiss Pediatric Oncology Group; Roland A Ammann, MD

Principal Investigators

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Roland A Ammann, MD

Role: STUDY_CHAIR

Pediatric Hematology/Oncology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland

Christoph Aebi, MD

Role: STUDY_DIRECTOR

University Children's Hospital, Bern, Switzerland

Maja Beck-Popovic, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Lausanne, Switzerland

Eveline SJM de Bont, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Groningen, The Netherlands

Thomas Kuehne, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Basel, Switzerland

David Nadal, MD

Role: STUDY_DIRECTOR

University Children's Hospital, Zurich

Felix Niggli, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland

Arne Simon, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Bonn, Germany

Nicole Bodmer, MD

Role: STUDY_DIRECTOR

Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland

Hulya Ozsahin, MD

Role: PRINCIPAL_INVESTIGATOR

Pediatric Hematology/Oncology, University Children's Hospital, Geneva, Switzerland

Locations

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Pediatric Hematology/Oncology, University Children's Hospital

Bonn, , Germany

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Düsseldorf, , Germany

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Freiburg im Breisgau, , Germany

Site Status

Pediatric Hematology/Oncology, University Children's Hospital von Hauner

Munich, , Germany

Site Status

Pediatric Hematology/Oncology, University Hospital St. Hedwig

Regensburg, , Germany

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Groningen, , Netherlands

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Basel, , Switzerland

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Bern, , Switzerland

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Geneva, , Switzerland

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Lausanne, , Switzerland

Site Status

Pediatric Hematology/Oncology, Children's Hospital

Lucerne, , Switzerland

Site Status

Pediatric Hematology/Oncology, University Children's Hospital

Zurich, , Switzerland

Site Status

Countries

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Germany Netherlands Switzerland

References

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Ammann RA. SPOG 2003 FN: Risikobeurteilung und risikoadaptierte Behandlung bei Kindern und Jugendlichen mit Fieber in Neutropenie. Paediatrica 16(1): 28-31, 2005.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 15747334 (View on PubMed)

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.

Reference Type RESULT
PMID: 20231680 (View on PubMed)

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.

Reference Type RESULT
PMID: 22271702 (View on PubMed)

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.

Reference Type RESULT
PMID: 21837771 (View on PubMed)

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.

Reference Type RESULT
PMID: 21394050 (View on PubMed)

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.

Reference Type RESULT
PMID: 25020130 (View on PubMed)

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.

Reference Type RESULT
PMID: 24618935 (View on PubMed)

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.

Reference Type RESULT
PMID: 26619462 (View on PubMed)

Related Links

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http://www.spog.ch

The Swiss Pediatric Oncology Group (SPOG) was the sponsor of this study.

Other Identifiers

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Umbrella Network Trial 2004.3

Identifier Type: -

Identifier Source: secondary_id

OCS - 01466-02-2004

Identifier Type: -

Identifier Source: secondary_id

SPOG 2003 FN

Identifier Type: -

Identifier Source: org_study_id