Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12610000407099
Ethics application status
Approved
Date submitted
18/05/2010
Date registered
21/05/2010
Date last updated
10/12/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
This is a randomised study to assess the safety and efficacy of a combined drug and orthopaedic standard care compared to the standard orthopaedic care and treatment for Perthes Disease in children.
Scientific title
A study to assess the safety and efficacy of bisphosphonate treatment in childhood femoral avascular necrosis due to Perthes Disease compared to the standard orthopaedic treatment and care.
Secondary ID [1] 251764 0
Nil
Universal Trial Number (UTN)
Trial acronym
Zoledronic Acid in Perthes (ZAP)Disease.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Avascular Necrosis due to Perthes Disease. 256930 0
Condition category
Condition code
Musculoskeletal 257073 257073 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1.An intravenous intervention of 0.025mg/Kg Zoledronic Acid (ZA) at each visit, the first being within 4 weeks of screening, then at 3 monthly intervals, (5 doses).
2.The calculated dose of reconstituted ZA will be diluted in 50ml of (0.9%) Normal Saline and infused over 30 minutes. The maximum dose to be given is 2 mg/infusion.
3. Vitamin D 400 International Units (IU) oral capsule supplementation daily for 15 months for duration of study
Intervention code [1] 256120 0
Treatment: Drugs
Comparator / control treatment
Standard treatment with Vitamin D 400 IU oral capsule supplementation daily for 24 months for duration of study.
Control group
Active

Outcomes
Primary outcome [1] 258420 0
To determine if 12 months of intravenous zoledronic acid improves femoral head sphericity in children and adolescents with Perthes disease. Deformity Index (DI) using Anteroposterior (AP) radiograph of the pelvis the DI compares the affected hip to the unaffected side. All measurements performed blinded at 24 months by a single observer.
Timepoint [1] 258420 0
At 24 months following randomisation.
Secondary outcome [1] 264192 0
To determine if 12 months of intravenous zoledronic acid improves hip function and pain in children and adolescents with Perthes disease. Assessment using the modified Harris Hip Score and Faces Pain Scale.
Timepoint [1] 264192 0
Baseline, 3,6,9,12,18 and 24 months visits.
Secondary outcome [2] 264193 0
To determine the safety of 12 months of intravenous zoledronic acid in children and adolescents with Perthes disease. Measured by: 1. Biochemistry and Haematology: urea, electrolytes, creatinine, calcium, magnesium, phosphorus and full blood count. Urine-Beta Human Chorionic Gonadotropin or Pregnancy Test (BHCG). Analysis will occur at the local treatment centre and be performed only on the intervention group (B) Mineral homeostasis and Bone turnover markers: 25-hydroxyvitamin D, parathyroid hormone (PTH), Serum Osteocalcin, Bone Specific Alkaline Phosphatase, aminoterminal propeptide of type 1 procollagen (P1NP), serum collagen-type I Ntelopeptides (NTX). These will be performed in both intervention (Group B) and control group (Group A) 2. Dual energy X-ray Absorptiometry (DXA scan): Lumbar spine, total body and bilateral femoral neck will be assessed. The magnitude of any increase in bone mass from ZA will be recorded. If age matched z-score for total body or lumbar spine becomes >3.0 ZA therapy will be discontinued. These will be performed in both intervention (Group B) and control group. (Group A) 3. Bone Age: There is a known delay in bone age in Perthes Disease. Radiographs will be evaluated by a single investigator. This will be performed in both intervention (Group A) and control group Group B) 4. Pelvic X-Ray.This will be performed in both intervention (Group A) and control group Group B) 4. Auxology: Height and Weight
Timepoint [2] 264193 0
Biochemistry and Haemotology: Baseline, 6,12 and 24 months visit. DXA Scan: Baseline, 12 and 24 months visit. Bone Age: Baseline, 12 and 24 months visit. X-Ray: Baseline,,12 and 24 months visit. Height and Weight: Baseline, 6,12 and 24 months visit.
Secondary outcome [3] 264194 0
To determine the Quality of Life of 12 months of intravenous zoledronic acid in children and adolescents with Perthes disease.
Assessment will be made using the Paediatric Outcomes Data Collection Instrument (PODCI)
Timepoint [3] 264194 0
Baseline, 6,12 and 24 months visit.
Secondary outcome [4] 264269 0
Femoral head subluxation (femoral head coverage) Extrusion can be measured as a percentage measured by AP X-ray.
Timepoint [4] 264269 0
At 24 months.

Eligibility
Key inclusion criteria
Diagnosis of unilateral Perthes Disease within the preceeding 6 months and with lateral pillar >50% of the contralateral side at the time of enrolment.
Minimum age
5 Years
Maximum age
16 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Diagnosis of Avascular Necrosis of the femoral head not due to Perthes Disease.
Previous treatment of bisphosphonates.
Current pregnancy or sexually active and not using a medically acceptable form of birth control.
Untreated rickets within 1 year of enrolment.
History of clinically significant organic or psychiatric findings on physical examination, which in the opinion of the investigator would prevent the patient from completing the study.
History of using any of the following medications: regardless of dose, for at least one month, within 3 months of enrolment: Anabolic agents, Calcitriol, Calcitonin, Fluroide (except dental health products), Glucocorticoids (does not include inhaled Glucocorticoids), Growth Hormone, Parathyroid hormone (PTH), Strontium, anticonvulsant medication.
At screening: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 upper limit of normal, thyroid-stimulating hormone (TSH) outside of the normal reference range, Vitamin D < 50nmol/l or Glommerula Filtration Rate (GFR) < 60 ml/min as per the Schwartz formula.

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)
Consent obtained after diagnosis of unlateral Perthes Disease with >50% involvement of the opposite lateral femoral head pillar for randomised treatment into either the a) Standard Care or b) intravenous Zoledronic Acid and Standard Care.
Allocation Concealment procedures using minimisation, with strata being gender, treating centre and age being conducted by phone at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be achieved via a web based system by the National Health and Medical Research Centre, Clinical Trials Centre.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/05/2010
Actual
12/01/2011
Date of last participant enrolment
Anticipated
31/12/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,WA,VIC
Recruitment postcode(s) [1] 2896 0
2145
Recruitment postcode(s) [2] 12432 0
4101 - South Brisbane
Recruitment postcode(s) [3] 12433 0
3052 - Parkville
Recruitment postcode(s) [4] 12434 0
5006 - North Adelaide
Recruitment postcode(s) [5] 12435 0
6840 - Perth
Recruitment outside Australia
Country [1] 7406 0
New Zealand
State/province [1] 7406 0
Auckland

Funding & Sponsors
Funding source category [1] 256960 0
Government body
Name [1] 256960 0
National Health and Medical Research Council
Country [1] 256960 0
Australia
Funding source category [2] 256961 0
Hospital
Name [2] 256961 0
The Royal Alexandria Hospital for Children
Country [2] 256961 0
Australia
Primary sponsor type
Hospital
Name
The Royal Alexandria Hospital for Children
Address
Cnr Hainsworth Street and Hawkesbury Road
Westmead 2145
NSW
Country
Australia
Secondary sponsor category [1] 256224 0
Commercial sector/Industry
Name [1] 256224 0
Novartis Australasia Pty Ltd
Address [1] 256224 0
PO Box 101
North Ryde NSW 2113
Country [1] 256224 0
Australia
Secondary sponsor category [2] 256225 0
Commercial sector/Industry
Name [2] 256225 0
BIOCeuticals and PharmaFoods
Address [2] 256225 0
16/37-41 O'Riordan Street
Alexandria NSW 2015
Country [2] 256225 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258980 0
The Royal Alexandria Hospital for CHildren Ethics Committee
Ethics committee address [1] 258980 0
Cnr Hainsworth and Hawkesbury Roads
Westmead NSW 2145
Ethics committee country [1] 258980 0
Australia
Date submitted for ethics approval [1] 258980 0
Approval date [1] 258980 0
29/05/2015
Ethics approval number [1] 258980 0
15/SCHN/127

Summary
Brief summary
This study is a randomised study that will investigate the safety and effacy of intravenous Zoledronic Acid and standard care compared to Standard Care in children and young adolescents, diagnosed with Perthes Disease.
The hypothesis is that 12 months of intravenous zoledronic acid will retard femoral head collapse resulting in: improved femoral head sphericity at 24 months and improved hip function and reduced hip pain at 24 months
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30845 0
Prof Chris Cowell
Address 30845 0
Director Kids Research Insititute
Sydney Children's Hospital Network(Westmead)
Cnr Hainsworth Street and Hawkesbury Road
Westmead NSW 2145
Country 30845 0
Australia
Phone 30845 0
+61 29845 3200
Fax 30845 0
Email 30845 0
[email protected]
Contact person for public queries
Name 14092 0
Professor Chris Cowell
Address 14092 0
Director The Kids Research Insitutue
The Children's Hospital at Westmead
Cnr Hainsworth Street and Hawkesbury Road
Westmead NSW 2145
Country 14092 0
Australia
Phone 14092 0
+61 2 9845 3200
Fax 14092 0
+61 2 9845 3170
Email 14092 0
[email protected]
Contact person for scientific queries
Name 5020 0
Professor David Little
Address 5020 0
Head Orthopaedics BioResearch
The Children's Hospital at Westmead
Cnr Hainsworth Street and Hawkesbury Road
Westmead NSW 2145
Country 5020 0
Australia
Phone 5020 0
+61 2 9845 0000
Fax 5020 0
+ 61 2 9845 3170
Email 5020 0
[email protected]

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

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