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Trial registered on ANZCTR


Registration number
ACTRN12609000459224
Ethics application status
Approved
Date submitted
10/03/2009
Date registered
15/06/2009
Date last updated
15/06/2009
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Randomised Control Trial Using Oral Antibiotics Following a Short Course of Intravenous Therapy in Children with Acute Osteomyelitis with or without Septic Arthritis
Scientific title
Early switch from intravenous to oral antibiotics in treatment of acute Paediatric Osteomyelitis
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteomyelitis in the paediatric population in New Zealand 4443 0
Condition category
Condition code
Infection 4712 4712 0 0
Studies of infection and infectious agents
Musculoskeletal 237298 237298 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous Cephazolin 50mg/kg every 8 hours or Flucloxacillin 50mg/kg every 6 hours until clinical defervescence, then change to high dose oral Cephalexin 25mg/kg every 6 hours. Antibiotics are given for a minimum 3 week duration. Weekly follow up programme until children are cured clinically, which will be the endpoint of antibiotic treatment . Children are anticipated to have no more that 6 weeks of antibiotics unless clincially indicated, with the reason clearly stated. Children are excluded from the study if they do not acheive clinical defervescence by 10 days.
Intervention code [1] 4189 0
Treatment: Drugs
Comparator / control treatment
Long duration, ie 3-6 weeks, of intravenous Flucloxacillin 50mg/kg every 6 hours or Cephazolin 50mg/kg every 8 hours, via peripherally inserted central catheter, given either by caregivers at home, or given as inpatient. Children will be given antibitoics for a minimun of 3 weeks, and be reviewed weekly to to monitor progress and determine endpoint of treatment. A maximum antibiotic duration of 6 weeks is anticipated unless clinically indicated, the reason for which will be clearly specified.
Control group
Active

Outcomes
Primary outcome [1] 5579 0
Time to disappearance of disease
1) Blood test - normalisation of C-reactive protein
2) Clinical examination - complete resolution of pain and site specific bone tenderness
3) Absence of fever
4) Radiological - no raiodlogical progression of osteomyelitis
Timepoint [1] 5579 0
at 3 and 6 week reviews from time of clinical defervescence.
Primary outcome [2] 5580 0
Time spent in hospital
Timepoint [2] 5580 0
12 months from presentation to hospital
Primary outcome [3] 5581 0
Recurrences of disease
1) Increase in C-reaction protein after defervescence with other symptoms and signs to indicate worsening of disease during tratment.
2) Fever >38 degrees on two occasions in a 24 hr period, with other cause of fever excluded during treatment
3) New xray change beyong expectation from the initial illness within 12 months from presentation
4) Positive blood cutlures relatedto the initial infection
5) Further surgical complications after defervescence
6) Non-resolution of initial symptoms including fever, bone or joint pain indicative of osteomyelitis +/- septic arthritis during course of treatment
7) Reappearance of inital symptoms including fever, bone or joint pain indicative of osteomylitis +/- septic arthritis after completion of treatment.
8) C reactive protein > or = 8 at the end of treatment, with other cause of inflamation or infection exlcuded
Timepoint [3] 5581 0
12 months from presentation to hospital
Secondary outcome [1] 9406 0
Rate of change in C-reactive Protein, which will be modelled using a general linear mixed model to allow for the within person correlation of measures over time, with group and time, plus their interaction as explanatory variables. The 95% confidence interval of the difference in the slopes will be formed.
Timepoint [1] 9406 0
at 6 weeks from defervescence of disease, or when antibiotic treatment is completed, whichever occurs sooner.
Secondary outcome [2] 242321 0
Adverse events which includes peripherally- inserted-central-catheter mechanical malfunction or infection, neutropenia secondary to antibiotic hypersensitivity, rash, gastrointestinal adverse effect, any other antibiotic side effect including intolerance of oral antibiotics.
Timepoint [2] 242321 0
at 12 months from presentation to hospital

Eligibility
Key inclusion criteria
Children who presented with a diagnosis of actute osteomyelitis with or without septic arthritis.
Osteomyelitis is defined as an acute disease with symptoms, clinical or radiological signs compatible with the disease, and with or without positive microbiology from a local bony lesion or blood culture.
Septic arthritis is defined by an acute disease with positive inflammatory or microbiology result in a joint aspirate.
Minimum age
6 Months
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Chronic osteomyelitis
2) Vertebral osteomyelitis
3) Atypical causative organism including gram negative bacteria and resistant organisms
4) Children with a history of compound fracture or penetrating injury
5) Immunodeficiency
6) Multifocal disease
7) Failure to achieve defervescence within 10-14 days from initiation of intravenous antibiotics
8) Children unable to take oral antibiotics
9) History of penicillin anaphylaxis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Children with be identified from the Starship daily admission sheet. Most children with suspected musculoskeletal infections will proceed to imaging and / or surgical aspiration or washout within 48 to 72 hours, and be started on intravenous antibiotics prior to or after the dianostic procedures. Once the diagnosis is confirmed, chidlren and their caregivers are approached for recruitment and consent for the study. Randomisation will occur once participants achive defervescence, which is defined by sustained reduction of temperature to normal levels and improvement of pain and symptoms. Allocation is concealed and performed by contacting the holder of allocation schedule who is off site and by computer. Recruitment is allowed from the time of diagnosis to defervescence. 100 children will be recruited into the study over a period of 2 years.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Once defervescence is achieved and all diagnostic tests are completed, randomisation by minimisation will be performed using variables including sex, age, and number of surgical procedures. Allocation is concealed. Characteristics of the new subject will be fed into a computer containing the file of characteristics of the children already enrolled in the study. The minimisation software will be run to allocate the new patient. Children are radomised to into 2 treatment groups.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/03/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment outside Australia
Country [1] 1660 0
New Zealand
State/province [1] 1660 0

Funding & Sponsors
Funding source category [1] 4636 0
Charities/Societies/Foundations
Name [1] 4636 0
Joan Mary Reynolds Charitable Trust
Country [1] 4636 0
New Zealand
Funding source category [2] 237125 0
Charities/Societies/Foundations
Name [2] 237125 0
Maurice & Phyllis Paykel Trust
Country [2] 237125 0
New Zealand
Primary sponsor type
Individual
Name
Diana Lennon
Address
Office 730-365, School of Population Health, Tamaki Campus, Building 730, 261 Morrin Road, Glen Innes,
Auckland 1130
Country
New Zealand
Secondary sponsor category [1] 4180 0
Individual
Name [1] 4180 0
Karen Tsui
Address [1] 4180 0
5.159, Level 5,
Starship Children's Hospital,
2 Park Road, Grafton,
Auckland 1023
Country [1] 4180 0
New Zealand
Other collaborator category [1] 607 0
Individual
Name [1] 607 0
Haemish Crawford
Address [1] 607 0
Department of Orthopaedics
Starship Children's Hospital
2 park Road, Grafton,
Auckland 1023
Country [1] 607 0
New Zealand
Other collaborator category [2] 608 0
Individual
Name [2] 608 0
Lesley Voss
Address [2] 608 0
Department of Paediatric Infectious Diseases
Starship Children's Hospital,
2 park Road, Grafton,
Auckland 1023
Country [2] 608 0
New Zealand
Other collaborator category [3] 609 0
Individual
Name [3] 609 0
Joanna Stewart
Address [3] 609 0
Office 730-448
School of Population Health,
Tamaki Campus,
Building 730, 261 Morrin Road,
Glen Innes, Auckland 1130
Country [3] 609 0
New Zealand
Other collaborator category [4] 610 0
Individual
Name [4] 610 0
Sue Stott
Address [4] 610 0
Department of Surgery,
Faculty of Medical and Health Sciences,
The University of Auckland,
Private Bag 92019
Auckland 1142
Country [4] 610 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 6674 0
Northern Y Regional Ethics Committee
Ethics committee address [1] 6674 0
Ethics committee country [1] 6674 0
New Zealand
Date submitted for ethics approval [1] 6674 0
28/11/2008
Approval date [1] 6674 0
Ethics approval number [1] 6674 0
NTY/08/12/114

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 29371 0
Address 29371 0
Country 29371 0
Phone 29371 0
Fax 29371 0
Email 29371 0
Contact person for public queries
Name 12618 0
Karen Tsui
Address 12618 0
Room 5.159
Starship Children's Hospital
2 Park Road, Grafton
Auckland 1023
Country 12618 0
New Zealand
Phone 12618 0
649 307 4949
Fax 12618 0
Email 12618 0
karent@adhb.govt.nz
Contact person for scientific queries
Name 3546 0
Karen Tsui
Address 3546 0
Room 5.159
Starship Children's Hospital
2 Park Road, Grafton,
Auckland 1023
Country 3546 0
New Zealand
Phone 3546 0
649 307 4949
Fax 3546 0
Email 3546 0
karent@adhb.govt.nz

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.