Rheumatoid ArthritisPhase 4TOCRIVARNCT01752335
Effect of Monoclonal Anti-IL6 Antibody (Tocilizumab) on the Cardiovascular Risk in Patients With Rheumatoid Arthritis
A Phase 4 study testing Braquial ecography in people with Rheumatoid Arthritis, run by Hospital Universitario de Canarias at 1 site in Spain.
Trial summary
The purpose of this study is to determine whether tocilizumab changes the cardiovascular risk factors on patients with arthritis rheumatoid. Study hypothesis: the IL-6 contributes to increase the cardiovascular risk factors of patients with rheumatoid arthritis because it produces systemic effects as increasing weight… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Braquial ecography
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteSpain
- Study dates
- Dec 2011to Mar 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 and <70 years.
- Diagnosis of active Rheumatoid Arthritis, moderate to severe (≥ 3.2 DAS28) of ≥ 6 months duration.
- Patients with an inadequate clinical response to a stable dose of non-biological DMARDs or anti-TNF treatment for a period ≥ 8 weeks before treatment.
- If patients are receiving oral corticosteroids, the dose should have been ≤ 10 mg predinosona and stable for at least one month before the start of treatment (day 1).
- Patients who are able and wish to sign the informed consent and comply with the requirements of the study protocol.
Who cannot join
- Major surgery (including joints surgery) within eight weeks prior to the screening visit or major surgery scheduled for six months after first infusion.
- Other Rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis or systemic involvement secondary to AR (such as vasculitis, pulmonary fibrosis or Felty's syndrome). It's allowed the inclusion of patients with interstitial pulmonary fibrosis and be still able to tolerate treatment with MTX. Sjögren's syndrome with RA is not considered exclusion criterion.
- Rheumatoid arthritis with Functional Class IV as defined in the RA Classification of the ACR (complete or significant disability of patients, confined to bed or to the wheelchair and without possibilities to take care themselves).
- Prior or actual inflammatory joint disease different of RA (eg, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease).
- Specific drug criteria
- Treatment with any investigational agent in the four weeks before the screening visit (or time equivalent to five half-lives of the investigational drug, whichever is longer).
Show all 33Show fewer
- Immunization with a live vaccine / attenuated in the four weeks prior to the baseline visit.
- Pretreatment with TCZ Laboratory Tests (at the screening visit)
- Serum creatinine> 142 mmol / l (1.6 mg / dL) in women and> 168 mmol / l (1.9 mg / dl) in men and absence of active renal disease.
- ALT (SGPT) and AST (SGOT)> 1.5 ULN (if the initial sample of ALT [SGPT] or AST [SGOT] gives a value> 1.5 times ULN, you can take and analyze a second sample during the selection period).
- Platelet count <100 x 109 / l (100.000/mm3).
- Hemoglobin <85 g / dl (<8.5 g / l, 5.3 mmol / l).
- Leukocytes <1.0 x 109 / l (1000/mm3), ANC <0.5 x 109 / L (500/mm3).
- RAL <0.5 x 109 / L (500/mm3).
- Positivity for surface antigen of hepatitis B (HBsAg) and antibodies to hepatitis C.
- Total bilirubin> ULN (if the initial sample of bilirubin> ULN, you can take and analyze a second sample during the selection period).
- Triglycerides> 10 mmol / l (> 900 mg / dl) at the screening visit (non fasting).
- Pregnant or lactating women.
- not use of reliable means of contraception, such as a physical barrier (patient and partner), pill or contraceptive patch, spermicide and barrier or IUD.
- Background of serious allergic or anaphylactic reactions to human monoclonal antibodies, humanized or murine.
- RXT evidence of clinically significant abnormality.
- Evidence of uncontrolled concomitant serious illness, cardiovascular, nervous system, lung (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), or gastrointestinal.
- history of diverticulitis, diverticulosis in antibiotic treatment, the physician should consider the benefit-risk ratio.
- Background of lower GI ulcer disease as the Crohn's disease, ulcerative colitis or other symptomatic conditions predisposed to perforations lower GI
- Uncontrolled diseases such as asthma, psoriasis or inflammatory bowel disease,... treated normally with corticosteroids orally or parenterally.
- Ongoing liver disease as determined by the principal investigator. (Patients with a history of elevated ALT (SGPT) will not be excluded)
- Active infections or recurrent infections in the past by mycobacteria, fungus, virus or bacteria (for example: tuberculosis, atypical mycobacterial disease, clinically significant abnormalities in RXT, hepatitis B and C, herpes zoster), or any major episode infection that required hospitalization or IV antibiotic treatment in the 4 weeks preceding the screening visit or oral antibiotic in the 2 weeks prior to the screening visit.
- Primary or secondary immunodeficiency.
- Evidence of active malignancy diagnosed within 5 years before the inclusion(including solid tumors and hematological), or breast cancer diagnosed in the previous 5 years.
- Active tuberculosis (TB) requiring treatment within 3 years above. Patients with a positive skin test tuberculin purified protein derivative (PPD) at the screening visit. Patients treated for tuberculosis no recurrence in the last three years will not be excluded.
- HIV positive patients.
- History of alcoholism, drug addiction or drug abuse in the six months before the screening visit.
- Painful neuropathies or other conditions that may interfere with the pain assessment.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitario de Canarias
San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320
About this study
The purpose of this study is to determine whether tocilizumab changes the cardiovascular risk factors on patients with arthritis rheumatoid.
Study hypothesis: the IL-6 contributes to increase the cardiovascular risk factors of patients with rheumatoid arthritis because it produces systemic effects as increasing weight and atherogenic body fat, changing energy homeostasis and inducing the adipokines production and the insulin resistence.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Braquial ecography
- Keywords
- Rheumatoid Arthritis, tocilizumab, cardiovascular risk factors
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Braquial ecographyOther
At the moment of the ecography, the clinician evaluates the endothelial responses via applying braquial ischemia and administering sublingual nitroglicerin spray to evaluate vasodilation.
| Study group | Role | What they receive |
|---|---|---|
| tocilizumab | Other | All the patients are treated with tocilizumab before inclusion. The doses, frequency and duration are in acordance with the Summary of Characteristics of the Product authorised by EMA.
Usually 8mg/kg (not minor than 480 mg), once each 4 weeks. Receives: Other: Braquial ecography |
What is being measured
The primary outcome is the main question the study is designed to answer.
Framingham Point Scores
Proportion of changes in Framingham Point Scores
Measured: Baseline and 52 weeks
Secondary outcomes (5)
Liver enzymes
Number of patients with liver enzymes elevated.
Measured: Baseline, 12, 24 and 52 weeks
Lipoprotein levels
Number of patients with elevated lipoprotein levels
Measured: Baseline, 12, 24 and 52 weeks
DAS28 score
Variation in DAS28 score after tocilizumab
Measured: Baseline and 52 week
Number of patients with Adverse Drug Reactions
Number of patients with Adverse Drug Reactions as a measure of safety
Measured: up to 52 weeks
Insulinemia
Change in insulinemia 52 weeks later.
Measured: Baseline and 52 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2012 (estimated)
- Study startDec 2011
- Primary completionMar 2017 (estimated)
- Study completionMar 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario de Canarias
- Sponsor type
- University, hospital or other
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Federico Díaz González, MD, PhD, Principal investigator, Hospital Universitario de Canarias
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01752335
- Sponsor's protocol ID
- FRC-TOC-2009-01
- Other IDs
- 2010-018658-12
- Acronym
- TOCRIVAR
- Status last verified
- Feb 2017
- First submitted
- 3 Dec 2012
- Last updated
- 9 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Monoclonal Anti-IL6 Antibody (Tocilizumab) on the Cardiovascular Risk in Patients With Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT01752335
- Acronym / sponsor ID
- TOCRIVAR / FRC-TOC-2009-01
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, tocilizumab, cardiovascular risk factors
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Hospital Universitario de CanariasUniversity, hospital or other
- Collaborators
- Roche Pharma AG
- Study start
- Dec 2011
- Primary completion
- Mar 2017 (estimated)
- Study completion
- Mar 2017 (estimated)
- First posted
- 19 Dec 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether tocilizumab changes the cardiovascular risk factors on patients with arthritis rheumatoid.
Study hypothesis: the IL-6 contributes to increase the cardiovascular risk factors of patients with rheumatoid arthritis because it produces systemic effects as increasing weight and atherogenic body fat, changing energy homeostasis and inducing the adipokines production and the insulin resistence.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| tocilizumab | Other | Other: Braquial ecographyAll the patients are treated with tocilizumab before inclusion. The doses, frequency and duration are in acordance with the Summary of Characteristics of the Product authorised by EMA. Usually 8mg/kg (not minor than 480 mg), once each 4 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 and <70 years.
- Diagnosis of active Rheumatoid Arthritis, moderate to severe (≥ 3.2 DAS28) of ≥ 6 months duration.
- Patients with an inadequate clinical response to a stable dose of non-biological DMARDs or anti-TNF treatment for a period ≥ 8 weeks before treatment.
- If patients are receiving oral corticosteroids, the dose should have been ≤ 10 mg predinosona and stable for at least one month before the start of treatment (day 1).
- Patients who are able and wish to sign the informed consent and comply with the requirements of the study protocol.
Key exclusion criteria (33 listed)
- Major surgery (including joints surgery) within eight weeks prior to the screening visit or major surgery scheduled for six months after first infusion.
- Other Rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis or systemic involvement secondary to AR (such as vasculitis, pulmonary fibrosis or Felty's syndrome). It's allowed the inclusion of patients with interstitial pulmonary fibrosis and be still able to tolerate treatment with MTX. Sjögren's syndrome with RA is not considered exclusion criterion.
- Rheumatoid arthritis with Functional Class IV as defined in the RA Classification of the ACR (complete or significant disability of patients, confined to bed or to the wheelchair and without possibilities to take care themselves).
- Prior or actual inflammatory joint disease different of RA (eg, gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease).
- Specific drug criteria
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Braquial ecographyAt the moment of the ecography, the clinician evaluates the endothelial responses via applying braquial ischemia and administering sublingual nitroglicerin spray to evaluate vasodilation. | Other | tocilizumab |
Primary outcome
Framingham Point Scores
Time frame: Baseline and 52 weeks
Proportion of changes in Framingham Point Scores
5 secondary outcomes
Liver enzymes
Time frame: Baseline, 12, 24 and 52 weeks
Lipoprotein levels
Time frame: Baseline, 12, 24 and 52 weeks
DAS28 score
Time frame: Baseline and 52 week
Number of patients with Adverse Drug Reactions
Time frame: up to 52 weeks
Insulinemia
Time frame: Baseline and 52 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2017.
Related trials for Rheumatoid Arthritis
RecruitingPhase 2
Study of PTC844 in Participants With Active Rheumatoid Arthritis
Rheumatoid Arthritis
Not yet recruitingPhase 1
An Ascending Dose Study of DKB903 in Participants With Rheumatoid Arthritis (RA) and Participants With Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis and Systemic Lupus Erythematosus
Not yet recruitingPhase 1
R-2487 in Patients With Sjogren's Syndrome (SjD)
Sjogren's Syndrome, Sjögren
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
Active, not recruitingPhase 2
A Study Evaluating the Safety and Efficacy of Inhaled AP01 in Participants With Progressive Pulmonary Fibrosis
Pulmonary Fibrosis, Progressive Pulmonary Fibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Federico Díaz González, MD, PhD principal investigator
Hospital Universitario de Canarias
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Braquial ecography in people with Rheumatoid Arthritis, run by Hospital Universitario de Canarias at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Framingham Point Scores (time frame: Baseline and 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2017.