Zoledronic Acid in Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

— AZAR  

Official title:

Randomized Clinical Trial on the Prevention of Radiographic Progression With Zoledronic Acid in Patients With Early Rheumatoid Arthritis and Low Disease Activity

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02123264
• Other study ID #: CGV222
• Status: Terminated
• Phase: Phase 3
• Start date: May 2014
• Est. completion date: June 2018

Study information

• Verified date: February 2019
• Source: Hospital Universitari de Bellvitge
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 28
• Est. completion date: June 2018
• Est. primary completion date: June 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age equal or greater than 18 years

2. Patients with RA of less than 2 years of evolution

3. DMARD therapy (methotrexate alone or methotrexate, leflunomide or methotrexate within COBRA strategy) on stable dose for at least 6 weeks prior to study entry

4. Patients not treated with glucocorticoids or under stable dose of prednisone up to 5 mg / day or equivalent dose of another glucocorticoid

5. Low disease activity (DAS28 <3.2)

6. In case of premenopausal women, commitment to make contraceptive treatment up to 3 years after the last dose of zoledronic acid

7. Signed informed consent

Exclusion Criteria:

1. Previous or current treatment with biological drugs used for the treatment of RA (infliximab, adalimumab, etanercept, certolizumab, golimumab, rituximab, abatacept, tocilizumab)

2. Pretreatment with:

1. Bisphosphonates in the 5 years prior to the onset of RA

2. Calcitonin, raloxifene, bazedoxifene, strontium ranelate, teriparatide and denosumab in the year before the onset of RA

3. Contraindication to treatment with zoledronic acid:

1. Hypersensitivity to bisphosphonates

2. Hypocalcemia

3. Glomerular filtration rate <35 mL / min

4. Pregnant (negative pregnancy test) and lactating women

5. Poor oral hygiene

6. Pending invasive dental procedure

4. Serum levels of calcidiol lower than 25 nmol/L (10 ng/mL).

5. Simultaneous participation in another clinical trial

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Zoledronic acid
Zoledronic acid: 5 mg/year x 2 years

Locations

Country	Name	City	State
Spain	Complexo Hospitalario Universitario A Coruña	A Coruña
Spain	Hospital Universitario de Cruces	Barakaldo	Bilbao
Spain	Hospital Clinic I Provincial de Barcelona	Barcelona
Spain	Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitari Son Espases	Palma de Mallorca	Mallorca
Spain	Hospital de Sant Joan Despí Moisés Broggi	Sant Joan Despí	Barcelona
Spain	Hospital Residència Sant Camil	Sant Pere de Ribes	Barcelona
Spain	Hospital Virgen Macarena	Sevilla
Spain	Hospital de Viladecans	Viladecans	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Carmen Gómez-Vaquero

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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