Back to resultsBonE and Joint Infections - Simplifying Treatment in Children Trial (BEST)
Primary Purpose
Bone Infection, Septic Arthritis, Bone and Joint Infection
Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Oral cefalexin only
IV cefazolin or IV flucloxacillin followed by oral cefalexin
Sponsored by
About this trial
This is an interventional treatment trial for Bone Infection
Eligibility Criteria
Inclusion Criteria:
- Children aged 1 to 18 years with acute, uncomplicated, community-acquired bone and joint infection who fulfil pre-defined clinical criteria.
Exclusion Criteria:
- Infection due to bacteria resistant to cefalexin or atypical infection (e.g. mycobacterial, fungal)
- Features of sepsis as defined by the presence of organ dysfunction (defined using definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)
- Concomitant severe, invasive infection e.g. necrosing fasciitis
- Complicated infection (e.g. presence of prosthetic material; subperiosteal or soft tissue abscess without surgical intervention; infection secondary to or complicated by trauma)
- History of allergy to cephalosporin antibiotics or immediate, severe reaction to penicillins
- Received more than three IV or oral dose of an antibiotic with activity against the likely bacteria causing the current infection
- Prior episode of OM or SA
- Prior condition predisposing to poor absorption (e.g. inflammatory bowel disease, current gastrointestinal symptoms) or complicated disease (e.g. immunodeficiency)
- Prior enrolment in the trial
- Current recipient of another investigational product as part of a clinical trial
Sites / Locations
- Sydney Children's Hospital Network
- The Children's Hospital at Westmead
- Royal Darwin Hospital
- Queensland Children's Hospital
- Women's and Children's Hospital
- The Royal Children's HospitalRecruiting
- Perth Children's Hospital
- Christchurch Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Intervention
Standard Therapy
Arm Description
Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) QID 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks
Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) or IV flucloxacillin 50 mg/kg/dise (max 2 g) four-times daily (QID) for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) three-times daily (TDS) for a total course of 3 weeks
Outcomes
Primary Outcome Measures
Proportion of children assessed as having made a full recovery 3 months
Full recovery is defined by the absence of:
(i) Clinical features of osteomyelitis or septic arthritis (ii) No episodes of disease recurrence requiring further antibiotic administration after initial treatment.
Assessment made by a qualified paediatrician.
Secondary Outcome Measures
Proportion of children with with recurrent disease at 6 months.
Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 3 months by an independent committee.
Proportion of children with with recurrent disease at 12 months.
Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 12 months by an independent committee.
Proportion of children with complications of their disease at 3 months.
Complications assessed by an independent committee defined as:
(i) residual dysfunction (ii) pain
Proportion of children with complications of their disease at 12 months.
Complications assessed by an independent committee defined as:
(i) residual poor function (ii) bone death (osteonecrosis) (iii) pain (iv) growth arrest (v) limb deformity
Proportion of children with treatment-related adverse effects (AEs).
Adverse effects assessed between days 1-7 including:
(i) Complications of IV access (eg need for replacement, infection, extravasation, drug side effects); or (ii) high-dose oral antibiotics (eg. drug side effects, inability to tolerate the full dose) It will be assessed between day 1-7 (can be at any time during the admission while intravenous antibiotics are prescribed)
Quality of life - Pediatric Quality of Life Inventory (PedsQL) 3 months
PedsQL is an acronym for the Pediatric Quality of Life Inventory. This inventory includes 23 items each scored 0 to 5 . The minimum score is 0 and the maximum score is 92. Lower scores indicate better quality of life. Outcome measures will be reported as median (range).
Quality of life - Child Health Utility Scale (CHU9D) Day 8-14
CHU9D is an acronym for the Child Health Utility scale. It includes 9 domains scored 0 to 5. The minimum score is 0 and the maximum is 5. The minimum score is 0 and the maximum is 45. Lower scores indicate better quality of life. Outcome measures will be reported as median (range). It will be administered once, and completed any day between Day 8 to Day 14.
Quality of life - Child Health Utility Scale (CHU9D) 12 months
CHU9D is an acronym for the Child Health Utility scale. It includes 9 domains scored 0 to 5. The minimum score is 0 and the maximum is 5. The minimum score is 0 and the maximum is 45. Lower scores indicate better quality of life. Outcome measures will be reported as median (range)
Quality of life - EQ-5d Day 8-14
EQ-5D is an acronym for the European Quality of Life Five Dimension, it is an instrument which evaluates the generic quality of life. It is a descriptive system with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Outcome measures will be reported as median (range). It will be administered once, and completed any day between Day 8 to Day 14.
Cost effectiveness - cost-effectiveness ratio of all resources at 12 months
The incremental cost-effectiveness ratio will be determined for both arms of the trial. This is a summary measure representing the economic value of the intervention (oral cefalexin), compared with the alternative (IV cefazolin followed by oral cefalexin). Estimated total sum of all hospital and patient/family resources required per patient per treatment course (AUD) collected by the study team at each study visit using a standard questionnaire (e.g. clinical services, medication, hospital and family accommodation, travelling, loss of income, care arrangements for family members). The mean total cost per treatment cost (AUD) will be reported for each arm of the trial.
Treatment adherence - medication reconciliation at 3 weeks
Mean percentage of cefalexin doses taken determined by medication reconciliation (ie. return of any remaining cefalexin) at end of treatment (3 weeks) assessed by the study team/trial pharmacist
Treatment adherence - Medication Adherence Response Scale at 3 weeks
Outcome will be reported as median adherence score (range 5-25).
Full Information
NCT ID
NCT04538053
First Posted
July 14, 2020
Last Updated
August 7, 2023
Sponsor
Murdoch Childrens Research Institute
1. Study Identification
Unique Protocol Identification Number
NCT04538053
Brief Title
BonE and Joint Infections - Simplifying Treatment in Children Trial
Acronym
BEST
Official Title
BonE and Joint Infections - Simplifying Treatment in Children Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Murdoch Childrens Research Institute
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a multi- centre trial of children with bone and joint infections (BJIs) at eight major paediatric hospitals in Australia and New Zealand. The primary objective is to establish if in children with acute, uncomplicated BJIs, entirely oral antibiotic treatment is not inferior to initial intravenous (IV) treatment for 1 to 7 days followed by an oral antibiotic course in achieving full recovery 3 months after presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or the 'standard treatment' group.
Detailed Description
Children with acute onset BJIs who present to the participating sites will be enrolled into the trial if eligible (see eligibility criteria) and randomly allocated into two groups. Children in the 'standard treatment group' will receive standard treatment for BJIs, which consists of IV antibiotics for 1-7 days followed by 3 weeks of oral antibiotics. Children in the 'entirely oral treatment group' will receive high dose oral antibiotics, followed by the standard dose of oral antibiotics for 3 weeks. The outcomes of children in each of the two groups will be compared to determine whether BJIs can be treated without needing a course of IV antibiotics.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bone Infection, Septic Arthritis, Bone and Joint Infection, Osteomyelitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
285 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) QID 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) TDS for a total course of 3 weeks
Arm Title
Standard Therapy
Arm Type
Active Comparator
Arm Description
Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) or IV flucloxacillin 50 mg/kg/dise (max 2 g) four-times daily (QID) for 1 to 7 days followed by oral cefalexin 45 mg/kg/dose (max 1.5 g) three-times daily (TDS) for a total course of 3 weeks
Intervention Type
Drug
Intervention Name(s)
Oral cefalexin only
Intervention Description
High-dose oral cefalexin
Intervention Type
Drug
Intervention Name(s)
IV cefazolin or IV flucloxacillin followed by oral cefalexin
Intervention Description
Standard therapy of IV cefazolin or IV flucloxacillin followed by high dose oral cefalexin
Primary Outcome Measure Information:
Title
Proportion of children assessed as having made a full recovery 3 months
Description
Full recovery is defined by the absence of:
(i) Clinical features of osteomyelitis or septic arthritis (ii) No episodes of disease recurrence requiring further antibiotic administration after initial treatment.
Assessment made by a qualified paediatrician.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Proportion of children with with recurrent disease at 6 months.
Description
Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 3 months by an independent committee.
Time Frame
6 months
Title
Proportion of children with with recurrent disease at 12 months.
Description
Proportion of children with recurrence of symptoms and signs after initial recovery requiring further antibiotic administration assessed at 12 months by an independent committee.
Time Frame
12 months
Title
Proportion of children with complications of their disease at 3 months.
Description
Complications assessed by an independent committee defined as:
(i) residual dysfunction (ii) pain
Time Frame
3 months
Title
Proportion of children with complications of their disease at 12 months.
Description
Complications assessed by an independent committee defined as:
(i) residual poor function (ii) bone death (osteonecrosis) (iii) pain (iv) growth arrest (v) limb deformity
Time Frame
12 months
Title
Proportion of children with treatment-related adverse effects (AEs).
Description
Adverse effects assessed between days 1-7 including:
(i) Complications of IV access (eg need for replacement, infection, extravasation, drug side effects); or (ii) high-dose oral antibiotics (eg. drug side effects, inability to tolerate the full dose) It will be assessed between day 1-7 (can be at any time during the admission while intravenous antibiotics are prescribed)
Time Frame
Between Day 1-7
Title
Quality of life - Pediatric Quality of Life Inventory (PedsQL) 3 months
Description
PedsQL is an acronym for the Pediatric Quality of Life Inventory. This inventory includes 23 items each scored 0 to 5 . The minimum score is 0 and the maximum score is 92. Lower scores indicate better quality of life. Outcome measures will be reported as median (range).
Time Frame
3 months
Title
Quality of life - Child Health Utility Scale (CHU9D) Day 8-14
Description
CHU9D is an acronym for the Child Health Utility scale. It includes 9 domains scored 0 to 5. The minimum score is 0 and the maximum is 5. The minimum score is 0 and the maximum is 45. Lower scores indicate better quality of life. Outcome measures will be reported as median (range). It will be administered once, and completed any day between Day 8 to Day 14.
Time Frame
Once between Day 8 to Day 14
Title
Quality of life - Child Health Utility Scale (CHU9D) 12 months
Description
CHU9D is an acronym for the Child Health Utility scale. It includes 9 domains scored 0 to 5. The minimum score is 0 and the maximum is 5. The minimum score is 0 and the maximum is 45. Lower scores indicate better quality of life. Outcome measures will be reported as median (range)
Time Frame
12 months
Title
Quality of life - EQ-5d Day 8-14
Description
EQ-5D is an acronym for the European Quality of Life Five Dimension, it is an instrument which evaluates the generic quality of life. It is a descriptive system with one question for each of the five dimensions that include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Outcome measures will be reported as median (range). It will be administered once, and completed any day between Day 8 to Day 14.
Time Frame
Once between Day 8 to Day 14
Title
Cost effectiveness - cost-effectiveness ratio of all resources at 12 months
Description
The incremental cost-effectiveness ratio will be determined for both arms of the trial. This is a summary measure representing the economic value of the intervention (oral cefalexin), compared with the alternative (IV cefazolin followed by oral cefalexin). Estimated total sum of all hospital and patient/family resources required per patient per treatment course (AUD) collected by the study team at each study visit using a standard questionnaire (e.g. clinical services, medication, hospital and family accommodation, travelling, loss of income, care arrangements for family members). The mean total cost per treatment cost (AUD) will be reported for each arm of the trial.
Time Frame
12 months
Title
Treatment adherence - medication reconciliation at 3 weeks
Description
Mean percentage of cefalexin doses taken determined by medication reconciliation (ie. return of any remaining cefalexin) at end of treatment (3 weeks) assessed by the study team/trial pharmacist
Time Frame
Week 3
Title
Treatment adherence - Medication Adherence Response Scale at 3 weeks
Description
Outcome will be reported as median adherence score (range 5-25).
Time Frame
Week 3
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Children aged 1 to 18 years with acute, uncomplicated, community-acquired bone and joint infection who fulfil pre-defined clinical criteria.
Exclusion Criteria:
Infection due to bacteria resistant to cefalexin or atypical infection (e.g. mycobacterial, fungal)
Features of sepsis as defined by the presence of organ dysfunction (defined using definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)
Concomitant severe, invasive infection e.g. necrosing fasciitis
Complicated infection (e.g. presence of prosthetic material; large subperiosteal (>3mm) or soft tissue abscess without surgical intervention; infection secondary to or complicated by trauma)
History of allergy to cephalosporin antibiotics or immediate, severe reaction to penicillins
Received more than three IV or oral dose of an antibiotic with activity against the likely bacteria causing the current infection
Prior episode of OM or SA
Prior condition predisposing to poor absorption (e.g. inflammatory bowel disease, current gastrointestinal symptoms) or complicated disease (e.g. immunodeficiency)
Prior enrolment in the trial
Current recipient of another investigational product as part of a clinical trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alison Boast, MD
Phone
+61393455522
Email
alison.boast@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Gwee, PhD
Phone
+61393455522
Email
amanda.gwee@rch.org.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Gwee, PhD
Organizational Affiliation
Murdoch Childrens Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sydney Children's Hospital Network
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brendan Mcmullan, Dr
Phone
293821241
Email
Brendan.Mcmullan@health.nsw.gov.au
Facility Name
The Children's Hospital at Westmead
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheryl Jones, Prof
Phone
+61418205848
Email
cheryl.jones@sydney.edu.au
Facility Name
Royal Darwin Hospital
City
Darwin
State/Province
Northern Territory
ZIP/Postal Code
0811
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joshua R Francis
Phone
+61423528381
Email
josh.francis@menzies.edu.au
Facility Name
Queensland Children's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4101
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clare Nourse, Prof
Phone
0413586954
Email
clare.nourse@health.qld.gov.au
Facility Name
Women's and Children's Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5006
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celia M Cooper, Dr
Phone
(08)81616396
Email
celia.cooper@sa.gov.au
Facility Name
The Royal Children's Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3051
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alison Boast, MD
Phone
+61395699551
Email
alison.boast@rch.org.au
First Name & Middle Initial & Last Name & Degree
Amanda Gwee, PhD
Phone
+61395699551
Email
amanda.gwee@rch.org.au
Facility Name
Perth Children's Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Asha Bowen, A/Prof
Phone
08 64562222
Email
asha.bowen@health.wa.gov.au
Facility Name
Christchurch Hospital
City
Christchurch
ZIP/Postal Code
8011
Country
New Zealand
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tony Walls, A/Prof
Email
tony.walls@otago.ac.nz
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The de-identified data set collected for this analysis of the BEST trial will be available six months after publication of the primary outcome.
The study protocol, analysis plan and consent forms will also be available. The data may be obtained from the Murdoch Children's Research Institute by emailing amanda.gwee@rch.org.au
IPD Sharing Time Frame
Time Frame: 6 months after publication of primary outcome
IPD Sharing Access Criteria
Prior to releasing any data the following are required: a data access agreement must be signed between relevant parties, the BEST Trial Principle and Associate Investigators must see and approve the analysis plan describing how the data will be analysed, there must be an agreement around appropriate acknowledgement and any additional costs involved must be covered. Data will only be shared with a recognised research institution which has approved the proposed analysis plan.
Learn more about this trial
BonE and Joint Infections - Simplifying Treatment in Children Trial
We'll reach out to this number within 24 hrs