BonE and Joint Infections - Simplifying Treatment in Children Trial

Phase 4RecruitingNCT04538053

Murdoch Childrens Research Institute285 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

285

Conditions

Bone Infection Septic Arthritis

Eligibility

Sex: ALLMin age: 1 YearMax age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

Nepean Hospital

Kingswood, New South Wales, Australia

RECRUITING

John Hunter Children's Hospital

New Lambton Heights, New South Wales, Australia

RECRUITING

Sydney Children's Hospital Network

Sydney, New South Wales, Australia

RECRUITING

The Children's Hospital at Westmead

Sydney, New South Wales, Australia

ACTIVE_NOT_RECRUITING

Royal Darwin Hospital

Darwin, Northern Territory, Australia

RECRUITING

Queensland Children's Hospital

Brisbane, Queensland, Australia

RECRUITING

Women's and Children's Hospital

Adelaide, South Australia, Australia

RECRUITING

The Royal Children's Hospital

Melbourne, Victoria, Australia

RECRUITING

Perth Children's Hospital

Perth, Western Australia, Australia

RECRUITING

Christchurch Hospital

Christchurch, New Zealand

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: 3 months

Secondary Outcomes

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.

Time frame: 6 months

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.

Time frame: 12 months

Proportion of children with complications of their disease at 3 months.

Complications assessed by an independent committee defined as: (i) residual dysfunction (ii) pain

Time frame: 3 months

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

Time frame: 12 months

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)

Time frame: Between Day 1-7

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).

Time frame: 3 months

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.

Time frame: Once between Day 8 to Day 14

Quality of life - Child Health Utility Scale (CHU9D) 12 months

Time frame: 12 months

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.

Time frame: Once 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.

Time frame: 12 months

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

Time frame: Week 3

Treatment adherence - Medication Adherence Response Scale at 3 weeks

Outcome will be reported as median adherence score (range 5-25).

Time frame: Week 3

BonE and Joint Infections - Simplifying Treatment in Children Trial

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts