Zoledronic Acid in Rheumatoid Arthritis
AZAR
Randomized Clinical Trial on the Prevention of Radiographic Progression With Zoledronic Acid in Patients With Early Rheumatoid Arthritis and Low Disease Activity
1 other identifier
interventional
28
1 country
11
Brief Summary
The progression of structural joint damage is the leading cause of disability and socioeconomic costs associated with rheumatoid arthritis (RA). Remission and low clinical activity not always imply absence of progression of structural damage. The main objective of this study is to evaluate the progression of radiological damage in early RA patients currently treated with disease modifying anti-rheumatic drugs (DMARDs) and low disease activity to which treatment with zoledronic acid is added. The investigators propose a randomized clinical trial in 94 patients with RA of less than 2 years of evolution that, being treated with DMARDs, present criteria of low disease activity (DAS28 \< 3.2). Patients will be randomized into two branches: zoledronic acid and no treatment. The primary study endpoint is the progression of radiological damage assessed in a blinded way by the difference in the Sharp-van der Heijde index (SHI) in radiographs of hands and feet after two years; the secondary variables: radiographic progression after one year, serum bone biomarkers (OPG, RANKL, DKK-1 and sclerostin) and adverse effects. In a subgroup of patients, the investigators shall evaluate the change in the size of hand erosions by multislice computed tomography and the evolution of periarticular osteoporosis and systemic bone mass by dual X-ray absorptiometry (DXA).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started May 2014
Typical duration for phase_3
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 23, 2014
CompletedFirst Posted
Study publicly available on registry
April 25, 2014
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2018
CompletedFebruary 22, 2019
February 1, 2019
4.1 years
April 23, 2014
February 21, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Sharp van der Heijde index
To assess the progression of radiographic damage in patients with early RA in current treatment with DMARDs and low disease activity to which treatment with zoledronic acid is added, compared to a no treatment control population, after two years.
Two years
Study Arms (2)
Zoledronic acid
ACTIVE COMPARATORZoledronic acid: 5 mg/year x 2 years
No intervention
NO INTERVENTIONNo intervention
Interventions
Eligibility Criteria
You may qualify if:
- Age equal or greater than 18 years
- Patients with RA of less than 2 years of evolution
- DMARD therapy (methotrexate alone or methotrexate, leflunomide or methotrexate within COBRA strategy) on stable dose for at least 6 weeks prior to study entry
- Patients not treated with glucocorticoids or under stable dose of prednisone up to 5 mg / day or equivalent dose of another glucocorticoid
- Low disease activity (DAS28 \<3.2)
- In case of premenopausal women, commitment to make contraceptive treatment up to 3 years after the last dose of zoledronic acid
- Signed informed consent
You may not qualify if:
- Previous or current treatment with biological drugs used for the treatment of RA (infliximab, adalimumab, etanercept, certolizumab, golimumab, rituximab, abatacept, tocilizumab)
- Pretreatment with:
- Bisphosphonates in the 5 years prior to the onset of RA
- Calcitonin, raloxifene, bazedoxifene, strontium ranelate, teriparatide and denosumab in the year before the onset of RA
- Contraindication to treatment with zoledronic acid:
- Hypersensitivity to bisphosphonates
- Hypocalcemia
- Glomerular filtration rate \<35 mL / min
- Pregnant (negative pregnancy test) and lactating women
- Poor oral hygiene
- Pending invasive dental procedure
- Serum levels of calcidiol lower than 25 nmol/L (10 ng/mL).
- Simultaneous participation in another clinical trial
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907, Spain
Hospital de Sant Joan Despí Moisés Broggi
Sant Joan Despí, Barcelona, 08970, Spain
Hospital Residència Sant Camil
Sant Pere de Ribes, Barcelona, 08810, Spain
Hospital de Viladecans
Viladecans, Barcelona, 08840, Spain
Hospital Universitario de Cruces
Barakaldo, Bilbao, 48903, Spain
Hospital Universitari Son Espases
Palma de Mallorca, Mallorca, 07120, Spain
Complexo Hospitalario Universitario A Coruña
A Coruña, 15006, Spain
Hospital Clinic I Provincial de Barcelona
Barcelona, 08036, Spain
Hospital Universitario de La Princesa
Madrid, 28006, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Hospital Virgen Macarena
Seville, 41071, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carmen Gómez-Vaquero, MD, PhD
Hospital Universitari de Bellvitge
- STUDY DIRECTOR
Silvia Pérez-Pujol, PhD
UCICEC-Hospital Universitari de Bellvitge
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- MD PhD
Study Record Dates
First Submitted
April 23, 2014
First Posted
April 25, 2014
Study Start
May 1, 2014
Primary Completion
June 1, 2018
Study Completion
June 1, 2018
Last Updated
February 22, 2019
Record last verified: 2019-02