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

NCT ID: NCT03576599

Last Updated: 2019-09-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-29
• Study Completion Date: 2019-06-26

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.

Conditions

Stress Fracture Foot; Stress Fracture Ankle

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Zoledronic Acid Injectable Product

Patients randomized to treatment with Zoledronic Acid 5mg infusion, repeated after 3 months

Group Type: ACTIVE_COMPARATOR

Zoledronic Acid Injectable Product

Intervention Type: DRUG

One Group are randomiced to Zoledronic Acid Injectable Product and one Group to Placebo

Placebo

Patients randomized to Placebo infusion (saline), repeated after 3 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Zoledronic Acid Injectable Product

One Group are randomiced to Zoledronic Acid Injectable Product and one Group to Placebo

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Aclasta

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Betanien Hospital

OTHER

Sponsor Role: collaborator

Sykehuset Ostfold

OTHER

Sponsor Role: collaborator

Oslo University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Elisabeth Ellingsen Husebye

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Elisabeth E Husebye, PhD

Role: STUDY_CHAIR

Oslo University Hospital

Locations

Oslo University Hospital

Oslo, , Norway

Countries

Norway

Other Identifiers

REK 2014/1986

Identifier Type: -

Identifier Source: org_study_id