|- candidate number||22389|
|- NTR Number||NTR5265|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||26-jun-2015|
|- Secondary IDs||47550 ABR, CCMO|
|- Public Title||Statins to Prevent Rheumatoid Arthritis (STAPRA)|
|- Scientific Title||Statins to Prevent Rheumatoid Arthritis (STAPRA)
Prevention of Rheumatoid Arthritis by Atorvastatin in Seropositive Arthralgia Patients: a Multicenter Double-Blind Randomized Placebo-Controlled Trial|
|- hypothesis||The use of atorvastatin in persons at high risk of RA is associated with a reduction in de development of arthritis|
|- Healt Condition(s) or Problem(s) studied||Rheumatoid arthritis|
|- Inclusion criteria||1) Age >= 18 years|
-IgM-RF and ACPA positive OR
-High ACPA titer (>3x cut-off)
3) With or without current joint pain, but without current clinical synovitis (ultrasound exam should not be performed in case of doubt, since US was shown to be often false-positive in this patient group)
4) Written informed consent
|- Exclusion criteria||1) Patients with synovitis during clinical examination (any of 44 joints of DAS) at inclusion or synovitis in the past during clinical examination by a rheumatologist. |
2) Patients with typical RA erosions on X-rays of hand and feet.
3) In case of inclusion depending on the presence of RF, the presence of situations with possible false-positive RF: known active infection with hepatitis C or Ebstein-Barr virus or recent radiotherapy.
4) Use of statins or other lipid-lowering agents within the last three months.
5) A history of previous use of statins discontinued due to side effects.
6) Patients with an indication for statin therapy according to local guidelines. All patients will be screened pior to randomisation, patients who fall into this category (SBD>180 mmHg, TC/HDL> 8.0 or have a cardiovasculair risk ¡Ã20% (only for patients between 40-70 years old) with SBD>140 mmHg and/ or LDL>2,5 mmol/L (see appendix H)) will be referred to the general practitioner with treatment advice).
7) Previous use of DMARDs other than hydroxychloroquine, or use of hydroxychloroquine within the last three months.
8) A history of oral or parenteral use of corticosteroids within the last 12 weeks used to treat the current episode of musculoskeletal symptoms.
9) Subjects with current severe, progressive, or uncontrolled hepatic disease (ALT>3x ULN), CK >3x ULN, hematologic disease, gastrointestinal disease, (diabetes with a serum glucose >7.0 mmol/L), pulmonary, cardiac, neurologic, or cerebral disease which, in the opinion of the investigator, might place a subject at unacceptable risk when participating in the study.
10) Subjects who are pregnant or who are breastfeeding or wish to become pregnant.
11) Subjects who currently abuse recreational drugs, or drink alcohol in excess (defined for the purposes of this trial as ¡Ã 21 units of alcohol per week; one unit = 1 glass of wine (125 mL) = 1 measure of spirits = ¡§ö pint of beer).
12) Subjects who have a limited life expectancy.
13) Subjects who are unable to fill out the questionnaires.
14) Subjects who are using ciclosporin (which interacts with statins).
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-aug-2015|
|- planned closingdate||1-jul-2020|
|- Target number of participants||220|
|- Interventions||Patients will be randomized for atorvastatin 40 mg or placebo tablets. Patients will be taken their medication for 3 years or until they develop arthritis|
|- Primary outcome||The occurrence of clinical arthritis confirmed by a rheumatologist participating in the study.|
|- Secondary outcome||Effect on improvement of lipid profile, (sub)clinical CV risk, inflammatory parameters and changes in cIMT and arterial stiffness.|
|- Timepoints||After inclusion at baseline patients will be monitored every 3 months for 3 years (in the outpatient clinic or by telephone). Then they will stop taking the medication and will receive one more visit after 1 year.|
|- Trial web site|
|- CONTACT FOR PUBLIC QUERIES||Dhr. D. Schaardenburg, van|
|- CONTACT for SCIENTIFIC QUERIES||Dhr. D. Schaardenburg, van|
|- Sponsor/Initiator ||Amsterdam Rheumatology & immunology Center, Reade|
(Source(s) of Monetary or Material Support)
|Reumafonds, Amsterdam Rheumatology & immunology Center, Reade|
|- Brief summary||Background and hypothesis|
Rheumatoid arthritis (RA) affects the joints and can lead to serious disability. In RA, a preclinical phase is often present, in which patients do not have arthritis, but do exhibit specific antibodies, often accompanied by vague joint symptoms and general symptoms. The existence of an at-risk phase enables us to investigate interventions with the goal of preventing the development of RA.
One of the major complications of RA is cardiovascular (CV) disease, which is doubled in comparison to the general population. Inflammation is thought to play an important role in this increased risk. Dyslipidaemia is also present, many years before RA becomes clinically apparent.
Therefore, we hypothesize that statin therapy, due to its combined lipid-lowering and anti-inflammatory effects, may be able to prevent the development of clinical arthritis in persons at increased risk for RA.
To investigate whether statin treatment can prevent or delay the development of clinical arthritis in persons at increased risk of RA.
Persons aged 18 years and older, who are either IgM-RF and ACPA positive or have a high ACPA titer (>3x ULN).
Multicenter double-blind randomized placebo-controlled trial.
Atorvastatin 40 mg or placebo OD will be given to 110 seropositive arthralgia patients in each arm during three years.
Main study parameters
The development of arthritis (¡Ý1 swollen joint) is the primary outcome measure. Serum lipids, calculated 10-year risk of cardiovascular events (in participants aged 40 years and over), changes in cIMT and arterial stiffness are secondary outcome measures.
|- Main changes (audit trail)|
|- RECORD||26-jun-2015 - 16-aug-2015|