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

Cancer Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00107081
• Other study ID #: SPOG 2003 FN
• Secondary ID: Umbrella Network
• Status: Terminated
• Phase: Phase 3
• Start date: January 2004
• Est. completion date: December 2007

Study information

• Verified date: October 2020
• Source: Swiss Pediatric Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 70
• Est. completion date: December 2007
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• Fever
• Neutropenia

Intervention

Drug:
• ciprofloxacin and amoxicillin

Procedure:
• Outpatient management

Drug:
• i.v. antibiotics

Procedure:
• inpatient management

Locations

Country	Name	City	State
Germany	Pediatric Hematology/Oncology, University Children's Hospital	Bonn
Germany	Pediatric Hematology/Oncology, University Children's Hospital	Duesseldorf
Germany	Pediatric Hematology/Oncology, University Children's Hospital	Freiburg
Germany	Pediatric Hematology/Oncology, University Children's Hospital von Hauner	Munich
Germany	Pediatric Hematology/Oncology, University Hospital St. Hedwig	Regensburg
Netherlands	Pediatric Hematology/Oncology, University Children's Hospital	Groningen
Switzerland	Pediatric Hematology/Oncology, University Children's Hospital	Basel
Switzerland	Pediatric Hematology/Oncology, University Children's Hospital	Bern
Switzerland	Pediatric Hematology/Oncology, University Children's Hospital	Geneva
Switzerland	Pediatric Hematology/Oncology, University Children's Hospital	Lausanne
Switzerland	Pediatric Hematology/Oncology, Children's Hospital	Lucerne
Switzerland	Pediatric Hematology/Oncology, University Children's Hospital	Zurich

Sponsors (4)

Lead Sponsor	Collaborator
Swiss Pediatric Oncology Group	Bayer, GlaxoSmithKline, Swiss Cancer League

Countries where clinical trial is conducted

Germany,  Netherlands,  Switzerland, 

References & Publications (9)

Agyeman P, Aebi C, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kühne 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 prospectiv — View Citation

Agyeman P, Kontny U, Nadal D, Leibundgut K, Niggli F, Simon A, Kronenberg A, Frei R, Escobar H, Kühne T, Beck-Popovic M, Bodmer N, Ammann RA. A prospective multicenter study of microbiologically defined infections in pediatric cancer patients with fever a — View Citation

Ammann RA, Bodmer N, Hirt A, Niggli FK, Nadal D, Simon A, Ozsahin H, Kontny U, Kühne T, Popovic MB, Lüthy AR, Aebi C. Predicting adverse events in children with fever and chemotherapy-induced neutropenia: the prospective multicenter SPOG 2003 FN study. J — View 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 Neutrop — View 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. — View 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. — View Citation

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

Brack E, Bodmer N, Simon A, Leibundgut K, Kühne 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 t — View Citation

Lüthi 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. 2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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%)
Primary	Efficacy: Response without rehospitalization or changing randomized antibiotics (non-inferiority design, limit 10%)
Secondary	Improved prediction of low-risk episodes of fever and neutropenia
Secondary	Description of characteristics of low-risk episodes of fever and neutropenia
Secondary	Description of characteristics of high-risk episodes of fever and neutropenia (observational study part)

External Links

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