SPOG 2015 FN Definition. A Multi-center Non-inferiority Trial on Safety of a High Versus Low Temperature Limit Defining Fever in Pediatric Patients With Cancer at Risk for Fever in Chemotherapy-induced Neutropenia

Cancer Clinical Trial

Official title:

SPOG 2015 FN Definition. A Swiss Pediatric Oncology Group (SPOG) Initiated Multi-center Open-label Randomized Controlled Multiple Crossover Non-inferiority Trial on Safety of a High Versus Low Temperature Limit Defining Fever in Pediatric Patients With Cancer at Risk for Fever in Chemotherapy-induced Neutropenia (FN)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02324231
• Other study ID #: SPOG 2015 FN Definition
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Est. completion date: September 15, 2018

Study information

• Verified date: October 2018
• Source: Swiss Pediatric Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In a multi-center open-label cluster-randomized controlled parallel-group multiple crossover non-inferiority trial in children and adolescents up to 20 years diagnosed with cancer requiring chemotherapy, primarily the safety, and secondarily the efficacy and other endpoints, of a high (39.0°C) versus low (38.5°C) temperature limit defining fever (TLDF) for the diagnosis of fever in chemotherapy-induced neutropenia (FN) is studied. Safety is assessed by the rate of safety relevant events per chemotherapy exposure time, a composite endpoint including serious medical complications and bacteremia during FN. Patients are repeatedly randomized (cluster: study site) to the high or the low TLDF every month, resulting in possible multiple crossovers in one patient. The high TLDF is declared not to be inferior regarding safety compared to the low TLDF if non-inferiority of the rate ratio of safety relevant events is proven, with a single-sided non-inferiority margin of 1.33, applying mixed Poisson regression.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 269
• Est. completion date: September 15, 2018
• Est. primary completion date: September 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

Inclusion Criteria:

• Chemotherapy treatment because of any malignancy for at least 2 months at time of recruitment for myelosuppressive therapy, or at least 1 cycle of myeloablative chemotherapy followed by autologous hematopoietic stem cell transplantation

• Age =12 months and <18 years at time of recruitment

• Written informed consent from patients and/or parents

Exclusion Criteria:

• Infants <1 years old (reason: differences in temperature measurement method)

• Past allogeneic hematopoietic stem cell transplantation

• Denied written informed consent from patients and/or parents

Related Conditions & MeSH terms

• Cancer
• Fever
• Fever in Neutropenia
• Neutropenia
• Pediatrics

Intervention

Other:
• 39.0°C temperature limit defining fever
Diagnosis of FN, correspondingly hospitalization and start of empirical intravenous broad-spectrum antimicrobial therapy. Further treatment according to treating physician.
• 38.5°C temperature limit defining fever
Diagnosis of FN, correspondingly hospitalization and start of empirical intravenous broad-spectrum antimicrobial therapy. Further treatment according to treating physician.

Locations

Country	Name	City	State
Switzerland	Basel: Universitätskinderklinik beider Basel	Basel
Switzerland	Bern: Universitätsklinik für Kinderheilkunde, Inselspital	Bern
Switzerland	Geneva: Département de Pédiatrie, Hôpital Cantonal de Genève	Geneva
Switzerland	Lausanne: Hémato-Oncologie Pédiatrique, CHUV	Lausanne
Switzerland	Luzern: Pädiatrische Hämatologie/Onkologie, Kinderspital	Lucerne
Switzerland	Zürich: Pädiatrische Onkologie Kinderspital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Swiss Pediatric Oncology Group

Country where clinical trial is conducted

Switzerland, 

References & Publications (1)

Ammann RA. A sequence of Swiss studies on the temperature Limit defining fever in pediatric oncology. Schweizer Krebsbulletin 35(1): 69-71, 2015.

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Development of rules predicting risk of FN during chemotherapy	Risk prediction rules for clinically defined FN, clinically defined FN with bacteremia, with serious medical complication, and with safety relevant event during chemotherapy, all based on multivariate mixed Poisson regression (stepwise forward variable selection procedure; unit: predictor)	1 year (estimated average)
Other	Development of rules predicting risk of adverse events during FN	Risk prediction rules for bacteremia, for serious medical complication, and for safety relevant event during FN, all based on multivariate mixed logistic regression (stepwise forward variable selection procedure; unit: predictor)	1 year (estimated average)
Other	External validation of rules predicting risk of FN during chemotherapy	Validation of published risk prediction rules for clinically defined FN, clinically defined FN with bacteremia, with serious medical complication, and with safety relevant event during chemotherapy (units: sensitivity, specificity, positive and negative predictive value, area under receiver operating characteristic curve)	1 year (estimated average)
Other	External validation of rules predicting risk of adverse events during FN	Validation of published risk prediction rules for bacteremia, for serious medical complication, and for safety relevant event during FN (units: sensitivity, specificity, positive and negative predictive value, area under receiver operating characteristic curve)	1 year (estimated average)
Primary	Rate of clinically defined FN with at least one safety relevant event	Poisson rate: number of clinically defined FN with at least one SRE divided by the entire chemotherapy exposure time for each patient, estimated to be 1 year on average (Unit: FN per year of chemotherapy exposure time) SRE: Composite endpoint (serious medical complication AND/OR bacteremia), reached until the end of each individual FN episode (Unit: binary)	1 year (estimated average)
Secondary	Times and delays of diagnosis and therapy (A)	Times (hh:mm) of measurement of fever - telephone to study site - arrival at emergency department - prescription of antibiotics - start and end of first dose of i.v. antibiotics (assessed per FN episode by the responsible local PHO and in patient chart, reported per FN episode; unit: hours:minutes)	1 year (estimated average)
Secondary	Adverse events (B)	AE: clinically / microbiologically documented infection, unexplained fever, sepsis / severe sepsis / septic shock, relapse of primary infection (assessed in patient charts, reported per FN; unit:binary)	1 year (estimated average)
Secondary	Delay from crossing low to high TLDF (C)	Only for currently active high TLDF: delay time between crossing low and high TLDF; delayed FN diagnosis (see 5.1.4) by high vs. low TLDF (assessed from patients charts, reported per FN; unit: hours:minutes)	1 year (estimated average)
Secondary	Rate of clinically defined FN (D)	Poisson rate: number of clinically defined FN divided by the entire chemotherapy exposure time for each patient, estimated to be 1 year on average (Unit: FN per year of chemotherapy exposure time)	1 year (estimated average)
Secondary	Rate of FN diagnosed at/above TLDF (E)	Poisson rate: number of FN diagnosed at/above TLDF divided by the entire chemotherapy exposure time for each patient, estimated to be 1 year on average (Unit: FN per year of chemotherapy exposure time)	1 year (estimated average)
Secondary	Rate of FN diagnosed below TLDF (E)	Poisson rate: number of FN diagnosed below TLDF divided by the entire chemotherapy exposure time for each patient, estimated to be 1 year on average (Unit: FN per year of chemotherapy exposure time)	1 year (estimated average)
Secondary	Duration of treatment (F)	. Duration of hospitalization, ICU treatment, i.v. antibiotics, p.o. antibiotics, any antibiotics, delay of chemotherapy for FN (unit: days)	1 year (estimated average)
Secondary	Simultaneous and avoided FN diagnoses (G)	Only for currently active high TLDF: Simultaneous and avoided FN diagnoses by high vs. low TLDF (assessed from patients charts, reported per FN; unit: binary)	1 year (estimated average)