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

NCT00107081 | Terminated Phase 3

• 3 other identifiers: SPOG 2003 FNUmbrella Network Trial 2004.3OCS - 01466-02-2004
• Study Type: interventional
• Target: 70
• Locations: 3 countries
• Sites: 12

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.

Conditions

Fever; Neutropenia; Cancer

Keywords

children; oral antibiotics; outpatient treatment; fever and neutropenia

Outcome Measures

Primary Outcomes (2)

• 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 (3)

• 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)

Study Arms (2)

Standard

ACTIVE COMPARATOR

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

Interventions

ciprofloxacin and amoxicillin DRUG

Experimental

Outpatient management PROCEDURE

Experimental

i.v. antibiotics DRUG

Standard

inpatient management PROCEDURE

Standard

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swiss Pediatric Oncology Group: lead
• Swiss Cancer League: collaborator
• Bayer: collaborator
• GlaxoSmithKline: collaborator

Study Sites (12)

Pediatric Hematology/Oncology, University Children's Hospital

Bonn, D-53113, Germany

Location

Pediatric Hematology/Oncology, University Children's Hospital

Düsseldorf, D-40225, Germany

Location

Pediatric Hematology/Oncology, University Children's Hospital

Freiburg im Breisgau, D-79106, Germany

Location

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

Munich, D-80337, Germany

Location

Pediatric Hematology/Oncology, University Hospital St. Hedwig

Regensburg, D-93049, Germany

Location

Pediatric Hematology/Oncology, University Children's Hospital

Groningen, NL-9700, Netherlands

Location

Pediatric Hematology/Oncology, University Children's Hospital

Basel, CH-4005, Switzerland

Location

Pediatric Hematology/Oncology, University Children's Hospital

Bern, CH-3010, Switzerland

Location

Pediatric Hematology/Oncology, University Children's Hospital

Geneva, CH-1205, Switzerland

Location

Pediatric Hematology/Oncology, University Children's Hospital

Lausanne, CH-1011, Switzerland

Location

Pediatric Hematology/Oncology, Children's Hospital

Lucerne, CH-6004, Switzerland

Location

Pediatric Hematology/Oncology, University Children's Hospital

Zurich, CH-8032, Switzerland

Location

Related Publications (9)

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

  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.

  PMID: 15747334 BACKGROUND

• 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.

  PMID: 20231680 RESULT

• 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.

  PMID: 22271702 RESULT

• 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.

  PMID: 21837771 RESULT

• 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.

  PMID: 21394050 RESULT

• 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.

  PMID: 25020130 RESULT

• 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.

  PMID: 24618935 RESULT

• 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.

  PMID: 26619462 RESULT

Related Links

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

MeSH Terms

Conditions

Fever; Neutropenia; Neoplasms

Interventions

Ciprofloxacin; Amoxicillin

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds

Study Officials

• Roland A Ammann, MD

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

  STUDY CHAIR

• Christoph Aebi, MD

  University Children's Hospital, Bern, Switzerland

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

• David Nadal, MD

  University Children's Hospital, Zurich

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

• Nicole Bodmer, MD

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

  STUDY DIRECTOR

• Hulya Ozsahin, MD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 4, 2005
• First Posted: April 5, 2005
• Study Start: January 1, 2004
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: November 2, 2020

Record last verified: 2020-10

Locations

CH (6); NL (1); DE (5)