Study on the ability of zoledronic acid to prevent worsening of radiographs of hands and feet of patients with rheumatoid arthritis diagnosed less than 2 years ago and who have few symptoms in their joints by making treatment with the drugs commonly used for the management of disease.

• Register: EUCTR
• Last refreshed on: 19 September 2016
• Main ID: EUCTR2013-005001-31-ES
• Date of registration: 07/02/2014
• Prospective Registration: Yes
• Primary sponsor: Dra. Carmen Gómez Vaquero (Servicio de Reumatología del Hospital Universiari de Bellvitge - Idibell)
• Public title: Study on the ability of zoledronic acid to prevent worsening of radiographs of hands and feet of patients with rheumatoid arthritis diagnosed less than 2 years ago and who have few symptoms in their joints by making treatment with the drugs commonly used for the management of disease.
• Scientific title: Randomized clinical trial on the prevention of radiographic progression with zoledronic acid in patients with early rheumatoid arthritis and low disease activity - Prevention of radiographic progression in rheumatoid arthritis with zoledronic acid
• Date of first enrolment: 25/03/2014
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005001-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: Blind third-party assessment If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: No treatment Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Spain

Contacts

• Name: Carmen Gómez-Vaquero
• Affiliation: Hospital Universitari de Bellvitge

• Name: Carmen Gómez-Vaquero
• Affiliation: Hospital Universitari de Bellvitge

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age ? 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. Im case of premenopausal women, commitment to make contraceptive treatment up to 3 years after the last dose of zoledronic acid
7. Signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 32

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:
a. Bisphosphonates in the 5 years prior to the onset of RA
b. Calcitonin, raloxifene, bazedoxifene, strontium ranelate, teriparatide and denosumab in the year before the onset of RA
3. Contraindication to treatment with zoledronic acid:
a. Hypersensitivity to bisphosphonates
b. Hypocalcemia
c. Glomerular filtration rate <35 mL / min
d. Pregnant (negative pregnancy test) and lactating women
e. Poor oral hygiene
f. Pending invasive dental procedure
4. Serum levels of calcidiol lower than 25 nmol/L (10 ng/mL).
5. Simultaneous participation in another clinical trial


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid arthritis
MedDRA version: 16.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Trade Name: Zoledronic acid
Product Name: Zoledronic acid
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ZOLEDRONIC ACID
CAS Number: 118072-93-8
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.8-

Primary Outcome(s)

Secondary Objective: a. To assess the progression of radiological damage after one year
b. To compare the loss of periarticular bone mass by DXA bone densitometry of the hands at two years
c. To compare general bone loss by DXA bone densitometry of lumbar spine and proximal femur at two years
d. To determine the size variation of carpal and metacarpophalangeal joints erosions by high resolution computed tomography (CT), at two years
e. To assess the predictive value of response to previous targets of serum OPG, RANKL, DKK-1 and sclerostin assets at the beginning.
f. To determine the proportion of patients that eventually require the addition of biological treatment for presenting sustained disease activity.
g. To determine the proportion of patients that eventually require the addition of biological treatment for presenting radiological progression.
h. To study the safety of zoledronic acid.

Primary end point(s): 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.

Main Objective: 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.

Timepoint(s) of evaluation of this end point: Baseline and after two years

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoints are specified for every secondary endpoint in section E.5.2.

Secondary end point(s): In patients with early RA in current treatment with DMARDs and low disease activity to whom zoledronic acid or no treatment is added:
a. To assess the progression of radiological damage after one year
b. To compare the loss of periarticular bone mass by DXA bone densitometry of the hands at two years
c. To compare general bone loss by DXA bone densitometry of lumbar spine and proximal femur at two years
d. To determine the size variation of carpal and metacarpophalangeal joints erosions by high resolution computed tomography (CT), at two years
e. To assess the predictive value of response to previous targets of serum OPG, RANKL, DKK-1 and sclerostin assets at the beginning of the study treatments.
f. To determine the proportion of patients that eventually require the addition of biological treatment for presenting sustained disease activity.
g. To determine the proportion of patients that eventually require the addition of biological treatment for presenting radiological progression.
h. To study the safety of zoledronic acid.

Secondary ID(s)

CGV222

Source(s) of Monetary Support

Ministerio de Economía y Competitividad