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Intravenous Bisphosphonate in Stress Fracture Treatment -A Randomised Controlled Double Blinded Multicenter Trial

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ClinicalTrials.gov Identifier: NCT03576599
Recruitment Status : Terminated (difficult to include patients)
First Posted : July 3, 2018
Last Update Posted : September 13, 2019
Sponsor:
Collaborators:
Betanien Hospital
Sykehuset Ostfold
Information provided by (Responsible Party):
Elisabeth Ellingsen Husebye, Oslo University Hospital

Tracking Information
First Submitted Date  ICMJE June 22, 2018
First Posted Date  ICMJE July 3, 2018
Last Update Posted Date September 13, 2019
Actual Study Start Date  ICMJE June 29, 2017
Actual Primary Completion Date June 26, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
The American Orthopedic Foot and Ankle Score (AOFAS) mid foot scale [ Time Frame: 1 year ]
a scale evaluating pain, function and alignment of the foot. 0-100, With 100 as maximum score
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
AOFAS mid foot scale [ Time Frame: 1 year ]
a scale evaluating pain, function and alignment of the foot
Change History Complete list of historical versions of study NCT03576599 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
  • Visual analoge scale (VAS) for pain [ Time Frame: 3, 6, 8, 10 and 12 months ]
    Patient Reported Outcome Measure (PROM) for evaluating local pain
  • Change in bone marrow lesions evaluated by magnetic resonance imaging (MRI) [ Time Frame: 1 year ]
    the intensity and the amount of bone marrow oedema is evaluated
  • The American Orthopedic Foot and Ankle Score (AOFAS) mid foot scale [ Time Frame: 3, 6, 8, 10, 12 months ]
    a scale evaluating pain, function and alignment of the foot
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2018)
  • VAS [ Time Frame: 3, 6, 8, 10 and 12 months ]
    PROM evaluating local pain
  • Change in bone marrow lesions evaluated by MRI [ Time Frame: 1 year ]
    the intensity and the amount of bone marrow oedema is evaluated
  • AOFAS mid foot scale [ Time Frame: 3, 6, 8, 10, 12 months ]
    a scale evaluating pain, function and alignment of the foot
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous Bisphosphonate in Stress Fracture Treatment -A Randomised Controlled Double Blinded Multicenter Trial
Official Title  ICMJE Intravenous Bisphosphonate in Stress Fracture Treatment
Brief Summary The effect of an intravenous bisphosphonate (zoledronic acid) on healing and symptoms of stress fractures that do not respond to conservative/conventional treatment within 6 months, will be investigated.
Detailed Description

Randomised controlled multicenter trial. Prospective study. The trial will be performed in accordance with the CONSORT-statement. The inclusion period will be two years. The patients will be randomised to standard treatment (casting, partial weight-bearing, orthotic insoles) in addition to either zoledronic acid or placebo (saline) infusions. The randomization process will be carried out through a web based randomization service (Norwegian University of Science and Technology, Unit for applied clinical research). Patient data will be kept and organized by a study coordinator (nurse) and will not be revealed for the clincal investigators, except in medical emergency situations. In such cases, the patient will be excluded from the study. A number of bottles containing zoledronic acid or placebo will be available in each of the participating hospitals. The bottles containing zoledronic acid and placebo are visually identical, numbered from 1 through 80 (two bottles with similar number, the second bottle will be kept for the second infusion). The patients will be randomised in blocks, creating evenly sized groups given zoledronic acid or placebo. When a patient is included and thereafter randomised, the study coordinator decides which bottle number to be given and provides this information to the physician. The study coordinator is the only person in the study group which is not blinded.

On the first visit, the included patients will undergo clinical examination and baseline parameters will be registered. If MRI is not previously obtained, this will be performed as quickly as possible. The clinical controls will be scheduled 4 and 12 and 26 weeks thereafter, the latter including MRI. If healing has still not occured, the patients will be given the second infusion and meet for clinical examination every 4 weeks until healing. Clinical healing is defined as painless or near painless (VAS pain 0-2) weight bearing. If healing has not occured 12 months after inclusion, surgery will be considered.

MRI will be obtained at (or before) baseline, 6 months and one year. MRIs will be examined by a blinded radiologist. Bone marrow lesions (BMLs) will be measured (area and volume) and fracture lines registered.

All patients (both groups) will be prescribed calcium and vitamin D (Calcigran Forte 500mg/400IE) taken orally once daily in the whole study period. This is recommended as an adjunct to bisphosphonate treatment on a general basis/standard treatment and is not to be investigated separately.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Stress Fracture Foot
  • Stress Fracture Ankle
Intervention  ICMJE
  • Drug: Zoledronic Acid Injectable Product
    One Group are randomiced to Zoledronic Acid Injectable Product and one Group to Placebo
    Other Name: Aclasta
  • Drug: Placebo
    Placebo
Study Arms  ICMJE
  • Active Comparator: Zoledronic Acid Injectable Product
    Patients randomized to treatment with Zoledronic Acid 5mg infusion, repeated after 3 months
    Intervention: Drug: Zoledronic Acid Injectable Product
  • Placebo Comparator: Placebo
    Patients randomized to Placebo infusion (saline), repeated after 3 months
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 11, 2019)
5
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2018)
40
Actual Study Completion Date  ICMJE June 26, 2019
Actual Primary Completion Date June 26, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 18-70 years
  • Stress fractures in the foot. A stress fracture is defined as a fracture occured after repetitive trauma, with characteristic MRI findings (ref) and distinctive pain over the fracture site at weight bearing.
  • at least 6 months of pain history
  • compliant patient
  • non-aided ambulatory patient prior to the injury

Exclusion Criteria:

  • Ongoing use of bisphosphonates, PTH/PTH-analogues or use within 12 months prior to the injury
  • Use of bisphophonates for more than 6 months within the last 5 years
  • Intolerance to zoledronic acid
  • Renal failure (GFR<30)
  • S-25(OH)vitD > 25
  • pregnancy
  • breast feeding
  • hypocalcemia
  • MRI contraindications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03576599
Other Study ID Numbers  ICMJE REK 2014/1986
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Elisabeth Ellingsen Husebye, Oslo University Hospital
Study Sponsor  ICMJE Oslo University Hospital
Collaborators  ICMJE
  • Betanien Hospital
  • Sykehuset Ostfold
Investigators  ICMJE
Study Chair: Elisabeth E Husebye, PhD Oslo University Hospital
PRS Account Oslo University Hospital
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP