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BonE and Joint Infections - Simplifying Treatment in Children Trial (BEST)

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ClinicalTrials.gov Identifier: NCT04538053
Recruitment Status : Recruiting
First Posted : September 3, 2020
Last Update Posted : September 16, 2021
Sponsor:
Information provided by (Responsible Party):
Murdoch Childrens Research Institute

Brief Summary:
This is a single centre trial of children with bone and joint infections (BJIs). 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 2 to 4 days followed by an oral antibiotic course in achieving full recovery 12 months after presentation. Children will be randomly allocated to the 'entirely oral antibiotic' group or the 'standard treatment' group.

Condition or disease Intervention/treatment Phase
Bone Infection Septic Arthritis Bone and Joint Infection Osteomyelitis Drug: Oral cefalexin only Drug: IV cefazolin followed by oral cefalexin Phase 4

Detailed Description:
Children with acute onset BJIs who present to the Royal Children's Hospital 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 2-4 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 214 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: BonE and Joint Infections - Simplifying Treatment in Children Trial
Actual Study Start Date : June 1, 2021
Estimated Primary Completion Date : September 2023
Estimated Study Completion Date : September 2023


Arm Intervention/treatment
Active Comparator: Intervention
Children will receive high-dose oral cefalexin 37.5 mg/kg/dose (max 1.5 g) four-times daily (QID) for 2 to 4 days followed by oral cefalexin 25 mg/kg/dose (max 1 g) QID for a total course of 3 weeks
Drug: Oral cefalexin only
High-dose oral cefalexin

Active Comparator: Standard Therapy
Children will receive IV cefazolin 50 mg/kg/dose (max 2 g) three-times daily (TDS) for 2 to 4 days followed by oral cefalexin 25 mg/kg/dose (max 1 g) four-times daily (QID) for a total course of 3 weeks
Drug: IV cefazolin followed by oral cefalexin
Standard therapy of IV cefazolin followed by high dose oral cefalexin




Primary Outcome Measures :
  1. Proportion of children assessed as having made a full recovery 3 months [ Time Frame: 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 :
  1. Proportion of children with with recurrent disease at 6 months. [ Time Frame: 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.

  2. Proportion of children with with recurrent disease at 12 months. [ Time Frame: 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.

  3. Proportion of children with complications of their disease at 3 months. [ Time Frame: 3 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


  4. Proportion of children with complications of their disease at 12 months. [ Time Frame: 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


  5. Proportion of children with treatment-related adverse effects (AEs). [ Time Frame: Day 4 ]

    Adverse effects assessed between days 2 - 4 by an independent review committee including:

    (i) complications of IV access (e.g. need for replacement, infection, extravasation, drug side effects); or (ii) high-dose oral antibiotics (e.g. drug side effects, inability to tolerate the full dose).


  6. Quality of life - Pediatric Quality of Life Inventory (PedsQL) Day 4 [ Time Frame: Day 4 ]

    Mean quality of life determined by PedsQL questionnaires administered between days 2 - 4 (while receiving initial IV or high-dose oral treatment) by the study team. The questionnaire will be asked of children if aged less over 7 years of age or the parent/guardian if the child is aged under 7 years of age.

    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.


  7. Quality of life - Child Health Utility Scale (CHU9D) Day 4 [ Time Frame: Day 4 ]

    Mean quality of life determined by CHU9D questionnaires administered between days 2 - 4 (while receiving initial IV or high-dose oral treatment) by the study team. The questionnaire will be asked of children if aged less over 7 years of age or the parent/guardian if the child is aged under 7 years of age.

    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.


  8. Cost effectiveness - cost-effectiveness ratio of all resources at 12 months [ Time Frame: 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.

  9. Treatment adherence - medication reconciliation at 3 weeks [ Time Frame: Week 3 ]
    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

  10. Treatment adherence - Morisky Medication Adherence Scale (MMAS) at 3 weeks [ Time Frame: Week 3 ]
    Mean Morisky Medication Adherence Scale (MMAS) score. This includes 8 questions and is scored from a minimum of 0 to a maximum of 8. The higher the score, the more likely the respondents were adherent to treatment.



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

  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; subperiosteal 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 one 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04538053


Contacts
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Contact: Alison Boast, MD +61393455522 alison.boast@gmail.com
Contact: Amanda Gwee, PhD +61393455522 amanda.gwee@rch.org.au

Locations
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Australia, Victoria
The Royal Children's Hospital Recruiting
Melbourne, Victoria, Australia, 3051
Contact: Alison Boast, MD    +61395699551    alison.boast@rch.org.au   
Contact: Amanda Gwee, PhD    +61395699551    amanda.gwee@rch.org.au   
Sponsors and Collaborators
Murdoch Childrens Research Institute
Investigators
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Principal Investigator: Amanda Gwee, PhD Murdoch Childrens Research Institute
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Responsible Party: Murdoch Childrens Research Institute
ClinicalTrials.gov Identifier: NCT04538053    
Other Study ID Numbers: 2019.287
First Posted: September 3, 2020    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: Time Frame: 6 months after publication of primary outcome
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.

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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
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Arthritis, Infectious
Osteomyelitis
Disease Attributes
Pathologic Processes
Arthritis
Joint Diseases
Musculoskeletal Diseases
Bone Diseases, Infectious
Bone Diseases
Cefazolin
Cephalexin
Anti-Bacterial Agents
Anti-Infective Agents