Clinical trial · Interventional

Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Children With Febrile Neutropenia

Safety and Efficacy of Ambulatory Versus In-hospital Antibiotic Treatment in Pediatric Patients With Cancer and Febrile Neutropenia: a Non-inferiority Multicenter Randomized Clinical Trial

NCT04000711CI-TRIAL-00039240completedN/AClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

Febrile neutropenia (FN) continues to be the infectious complication that most commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy. In recent years, data have been published on the effectiveness of treatment of FN events with oral antibiotics, mainly in developed countries, but data from developing countries continue to be scarce. Our hypothesis was that early change from initial in-patient intravenous antibiotic treatment to oral outpatient antibiotic treatment in children with cancer and FN is as safe and effective as in-patient intravenous antibiotic management. The purpose of this clinical study was to determine whether early outpatient oral antibiotic treatment is not inferior in safety and efficacy to in-hospital intravenous antibiotic treatment in pediatric patients with cancer and low-risk FN events. A multicenter, non-inferiority randomized clinical trial was conducted in three public hospitals in Mexico City. Low-risk FN events were identified in children aged 1 to 18 years. After 48 to 72 hours of receiving intravenous in-hospital antibiotics, children were randomly allocated to receive outpatient oral treatment (cefixime) or to continue in-hospital intravenous treatment (cefepime). Daily monitoring was performed until the resolution of neutropenia. Our outcome of interest was the presence of any unfavorable clinical outcome.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Chemotherapy-Induced Febrile Neutropenia	—	UNRESOLVED	—

Interventions

Interventions (2)

Intervention	Type	Mapped drug	Match
Inpatient intravenous treatment.	Other	—	UNRESOLVED
Outpatient oral treatment.	Other	—	UNRESOLVED

Design

Arms and outcomes

Arms (2)

type
EXPERIMENTAL
label
Outpatient oral antibiotic treatment group.
description
After randomization, participants assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day were discharged. Treatment was provided by the researchers. Subjects were evaluated daily at the outpatient clinic of the hospital. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed in the outpatient group, they were re-admitted to the hospital to receive intravenous antibiotics. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.
interventionNames
1. Other: Outpatient oral treatment.
type
ACTIVE_COMPARATOR
label
Inpatient intravenous antibiotic treatment group.
description
After randomization, participants continued intravenous inpatient antibiotic with cefepime 150 mg/kg/day according to local standard of care guidelines. Subjects were evaluated daily. All patients underwent a blood count every 48 to 72 hours. FN event resolution was defined as when the patient remained afebrile and the ANC increased to above 500 per microliter. If fever resumed, treatment was changed according to clinical guidelines. Resolution of the FN event was defined as the end of participation of the subjects in the study, and they were followed up for an additional 72 hours.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 1 Year
Maximum age: 18 Years

Show eligibility criteria text

Inclusion Criteria:

* Children from 1 to 18 years of age.
* Underlying cancer diagnosis that presented with fever and neutropenia secondary to chemotherapy and after 48-72 hours of inpatient intravenous treatment with Cefepime, were hemodynamically stable, remained afebrile for at least 24 hours, and did not have a documented source of infection.
* Participants whose caretaker knew how to read and write and accepted to be part of the clinical trial.

Exclusion Criteria:

* Participants with positive cultures.
* Absolute neutrophil count (ANC) \< 100/mm3.
* Thrombocytopenia \< 30,000/mm3.
* Less than 7 days have passed from the start of the last chemotherapy session.
* Leukemia on remission induction therapy.
* Relapsed leukemia.
* Mucositis grade III or IV.
* Participants with allergy to cefixime.
* Need to receive any other medication intravenously.
* Need of oxygen support, parenteral nutrition or intravenous fluids.
* Oral intolerance.

References

Publications (9)

BACKGROUNDFreifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073. PMID 21258094
BACKGROUNDSantolaya ME, Rabagliati R, Bidart T, Paya E, Guzman AM, Morales R, Braun S, Bronfman L, Ferres M, Flores C, Garcia P, Letelier LM, Puga B, Salgado C, Thompson L, Tordecilla J, Zubieta M; Sociedad Chilena de Infectologia; Sociedad Chilena de Hematologia. [Consensus: Rational approach towards the patient with cancer, fever and neutropenia]. Rev Chilena Infectol. 2005;22 Suppl 2:S79-113. Epub 2005 Nov 4. Spanish. PMID 16311689
BACKGROUNDLehrnbecher T, Phillips R, Alexander S, Alvaro F, Carlesse F, Fisher B, Hakim H, Santolaya M, Castagnola E, Davis BL, Dupuis LL, Gibson F, Groll AH, Gaur A, Gupta A, Kebudi R, Petrilli S, Steinbach WJ, Villarroel M, Zaoutis T, Sung L; International Pediatric Fever and Neutropenia Guideline Panel. Guideline for the management of fever and neutropenia in children with cancer and/or undergoing hematopoietic stem-cell transplantation. J Clin Oncol. 2012 Dec 10;30(35):4427-38. doi: 10.1200/JCO.2012.42.7161. Epub 2012 Sep 17. PMID 22987086
BACKGROUNDSantolaya ME, Alvarez AM, Aviles CL, Becker A, Cofre J, Enriquez N, O'Ryan M, Paya E, Salgado C, Silva P, Tordecilla J, Varas M, Villarroel M, Viviani T, Zubieta M. Prospective evaluation of a model of prediction of invasive bacterial infection risk among children with cancer, fever, and neutropenia. Clin Infect Dis. 2002 Sep 15;35(6):678-83. doi: 10.1086/342064. Epub 2002 Aug 23. PMID 12203164
BACKGROUNDHakim H, Flynn PM, Srivastava DK, Knapp KM, Li C, Okuma J, Gaur AH. Risk prediction in pediatric cancer patients with fever and neutropenia. Pediatr Infect Dis J. 2010 Jan;29(1):53-9. doi: 10.1097/INF.0b013e3181c3f6f0. PMID 19996816