BonE and Joint Infections - Simplifying Treatment in Children Trial

Osteomyelitis Clinical Trial

— BEST  

Official title:

BonE and Joint Infections - Simplifying Treatment in Children Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04538053
• Other study ID #: 2019.287
• Status: Recruiting
• Phase: Phase 4
• Start date: June 1, 2021
• Est. completion date: December 2026

Study information

• Verified date: August 2023
• Source: Murdoch Childrens Research Institute
• Contact: Alison Boast, MD
• Phone: +61393455522
• Email: alison.boast[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 285
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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:

1. Infection due to bacteria resistant to cefalexin or atypical infection (e.g. mycobacterial, fungal)

2. Features of sepsis as defined by the presence of organ dysfunction (defined using definitions within the Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score)

3. Concomitant severe, invasive infection e.g. necrosing fasciitis

4. 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)

5. History of allergy to cephalosporin antibiotics or immediate, severe reaction to penicillins

6. Received more than three IV or oral dose of an antibiotic with activity against the likely bacteria causing the current infection

7. Prior episode of OM or SA

8. Prior condition predisposing to poor absorption (e.g. inflammatory bowel disease, current gastrointestinal symptoms) or complicated disease (e.g. immunodeficiency)

9. Prior enrolment in the trial

10. Current recipient of another investigational product as part of a clinical trial

Related Conditions & MeSH terms

• Arthritis, Infectious
• Bone and Joint Infection
• Bone Infection
• Communicable Diseases
• Infections
• Osteomyelitis
• Septic Arthritis

Intervention

Drug:
• Oral cefalexin only
High-dose oral cefalexin
• IV cefazolin or IV flucloxacillin followed by oral cefalexin
Standard therapy of IV cefazolin or IV flucloxacillin followed by high dose oral cefalexin

Locations

Country	Name	City	State
Australia	Women's and Children's Hospital	Adelaide	South Australia
Australia	Queensland Children's Hospital	Brisbane	Queensland
Australia	Royal Darwin Hospital	Darwin	Northern Territory
Australia	The Royal Children's Hospital	Melbourne	Victoria
Australia	Perth Children's Hospital	Perth	Western Australia
Australia	Sydney Children's Hospital Network	Sydney	New South Wales
Australia	The Children's Hospital at Westmead	Sydney	New South Wales
New Zealand	Christchurch Hospital	Christchurch

Sponsors (1)

Lead Sponsor	Collaborator
Murdoch Childrens Research Institute

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3 months
Secondary	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.	6 months
Secondary	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.	12 months
Secondary	Proportion of children with complications of their disease at 3 months.	Complications assessed by an independent committee defined as: (i) residual dysfunction (ii) pain	3 months
Secondary	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	12 months
Secondary	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)	Between Day 1-7
Secondary	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).	3 months
Secondary	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.	Once between Day 8 to Day 14
Secondary	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)	12 months
Secondary	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.	Once between Day 8 to Day 14
Secondary	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.	12 months
Secondary	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	Week 3
Secondary	Treatment adherence - Medication Adherence Response Scale at 3 weeks	Outcome will be reported as median adherence score (range 5-25).	Week 3