Chemotherapy-Induced Febrile Neutropenia Clinical Trial
Official title:
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
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.
Introduction: Febrile neutropenia (FN) continues to be the infectious complication that most
commonly requires hospitalization in pediatric cancer patients undergoing chemotherapy.
Classically these patients have been managed as inpatient. 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.
Hypothesis: 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.
Objectives: 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.
Methodology: 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.
A complete medical history, physical examination and review of laboratory tests and cultures
were performed on all subjects with FN events who were considered low risk. According to
local guidelines for the treatment of FN, all subjects began receiving cefepime at a dose of
150 mg/kg/day. Subjects were followed-up daily, and those who met the inclusion/exclusion
criteria after 48 to 72 hours of in-hospital intravenous treatment with cefepime were
randomly assigned to receive outpatient treatment with oral cefixime at a dose of 8 mg/kg/day
or to continue in-hospital intravenous treatment. The treatment was administered by the
researchers.
Participants in both treatment groups were evaluated daily by a complete physical
examination. Subjects in the outpatient group were evaluated 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 absolute neutrophil count (ANC)
increased to above 500 per microliter. If fever resumed, the antibiotic regimen was modified.
If the subjects were 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.
The occurrence of any of the following conditions was considered an unfavorable clinical
outcome: 1) therapeutic failure, defined as the resumption of fever in a patient with
persistent neutropenia. For all patients with resumption of fever, the antibiotic regimen was
switched, and if the patients were in the outpatient treatment group, they were re-admitted
to the hospital; 2) new focus of infection, documented both by the clinical condition and by
laboratory and other diagnostic tests; 3) hemodynamic instability, defined as a decrease in
blood pressure below the 5th percentile for the patient age that did not revert with the
administration of crystalloid solutions; and 4) death.
Sample size: The sample size was calculated to reject a null hypothesis of inferiority, with
a non-inferiority margin of presentation of unfavorable clinical outcomes of 15%. A formula
including a statistical power of 80% and a one-tailed alpha value of 0.025 was used to
calculate the sample size of 2 independent proportions. Based on previous reports of 10% of
unfavorable clinical outcomes during the management of FN events, the calculation yielded a
total of 63 FN events per group for a total of 126 events.
Randomization: A random sequence balanced by blocks of 4 FN events was generated using a
computer program. A physician who did not participate in the subject selection assigned
subjects to receive either outpatient oral treatment at home or to continue in-hospital
intravenous treatment. If the subjects lived more than 1 hour away from the hospital, they
were assigned to a care home to ensure that they could return to the hospital in case of any
event. Because the study intervention involved outpatient treatment, the study was open. All
patients were provided with the antibiotic free of charge.
Statistical analysis: The focus of analysis was intention-to-treat. For each comparison
group, measures of central tendency and dispersion were estimated for continuous variables,
and absolute and relative frequencies were determined for discrete and nominal variables. The
statistical test performed to test the hypothesis of non-inferiority is very similar to the
traditional test for comparison of proportions; the only difference is that the
non-inferiority margin is added to the formula, and a p-value < 0.05 confirms
non-inferiority. The statistical program STATA version 14.2 was used for the analysis.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02467868 -
Efficacy and Safety Study With MYL-1401H and Neulasta
|
Phase 3 | |
| Completed |
NCT02178475 -
Prospective Observational Study of Febrile Neutropenia (FN) and Pegfilgrastim Primary Prophylaxis in Breast Cancer and Non-Hodgkin's Lymphoma Patients Receiving High (>20%) FN-risk Chemotherapy
|
||
| Recruiting |
NCT03823950 -
Starting Granulocyte Colony-Stimulating Factor at 1 Day vs 3 Days Following Chemotherapy in Pediatric Cancer Patients
|
Phase 4 | |
| Completed |
NCT01813721 -
Study Investigating How Physicians Assess the Risk of Patients Developing Febrile Neutropenia During Chemotherapy.
|
N/A |