TRial of Atorvastatin for the primary prevention of Cardiovascular Events in Rheumatoid Arthritis

ISRCTN	ISRCTN41829447
DOI	https://doi.org/10.1186/ISRCTN41829447
Secondary identifying numbers	N/A

Submission date: 14/06/2006
Registration date: 26/07/2006
Last edited: 06/02/2020

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Musculoskeletal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Study website

Contact information

Dr George Kitas
Scientific

Department of Rheumatology
Dudley Group of Hospitals NHS Trust
Russells Hall Hospital
Dudley
DY1 2HQ
United Kingdom

Phone	+44 (0)1384 244842
Email	g.d.kitas@bham.ac.uk

Study information

Study design	Multicentre randomised double-blind placebo-controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Patient information can be found at: http://www.dgoh.nhs.uk/tracera/gp_patientflyer.asp
Scientific title	TRial of Atorvastatin for the primary prevention of Cardiovascular Events in Rheumatoid Arthritis
Study acronym	TRACE/RA
Study hypothesis	The principal research question is to establish whether atorvastatin, used in conjunction with standard therapy for rheumatoid arthritis will protect rheumatoid arthritis sufferers aged 40 years and above from fatal and non-fatal atherosclerotic events. Please note that as of 30/04/2008 this trial was updated. All changes can be found in the relevant field under the above date. Please also note that the overall trial start and end dates have been updated. The previous dates of this trial were: Previous overall trial start date: 01/12/2006 Previous overall trial end date: 01/12/2014
Ethics approval(s)	Southampton and South West Hampshire Research Ethics Committee B, 20/12/2006, ref: 06/Q1704/171
Condition	Rheumatoid arthritis
Intervention	Patients will be randomised to either the atorvastatin arm (40 mg of atorvastatin oral tablet taken once daily) or placebo arm (placebo atorvastatin oral tablet taken once daily) of the trial.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Atorvastatin
Primary outcome measure	Cardiovascular primary endpoint for all patients: all cardiovascular events (analysed by time to FIRST event) briefly defined as: fatal myocardial infarction, other acute coronary heart disease death, definite or probable hospital-verified non-fatal acute myocardial infarction, resuscitated cardiac arrest, definite silent myocardial infarction verified by an electrocardiogram (ECG), coronary revascularisation procedures, hospital admission for acute coronary syndrome, fatal stroke or peripheral arterial event (using predefined standard definitions) and hospital-verified non-fatal stroke or peripheral atherosclerotic events. The endpoints assessment committee will adjudicate this. Rheumatology primary outcome (disease activity substudy only): Disease Activity Score 28 (DAS28) at six months, response will be judged using the European League Against Rheumatism (EULAR) response criteria.
Secondary outcome measures	Secondary endpoints for all patients: 1. All-cause mortality 2. Changes in fasting lipids and C-Reactive Protein (CRP) 3. Functional outcome (assessed by the Health Assessment Questionnaire [HAQ] and EuroQoL instrument [EQ5D]) 4. Statin safety-related outcomes. Rheumatology secondary outcomes (disease activity substudy only): Disease-Modifying Anti-Rheumatic Drug (DMARD) changes, DAS28 at years one, two and five. Not applicable as of 30/04/2008: Radiological outcome (assessed by the Larsen score in X-rays of hands and wrists - only at year two.
Overall study start date	07/08/2007
Overall study end date	01/08/2014

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	3,700 (3,808 as of 30/04/2008)
Total final enrolment	3002
Participant inclusion criteria	Current inclusion criteria as of 30/04/2008: 1. Patients must satisfy the 1987 ACR criteria for rheumatoid arthritis applied cumulatively 2. Patients must be aged more than 50 or have had RA disease duration for more than 10 years 3. Patients must provide their written informed consent Previous inclusion criteria: 1. Patients must satisfy the 1987 ACR criteria for rheumatoid arthritis applied cumulatively 2. Patients must be 40 years or older 3. Patients must provide their written informed consent
Participant exclusion criteria	Current exclusion criteria as of 30/04/2008: 1. Patients who are pregnant or women of child-bearing age not using adequate contraception 2. Known primary muscle disorder 3. Known atherosclerotic disease 4. Known familial hyperlipidamia requiring drug therapy 5. Known diabetes 6. Known hypersensitivity or intolerance to statins 7. Active liver disease or hepatic dysfunction with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) more than two times Upper Limit of Normal (ULN) 8. Severe renal dysfunction (creatinine >150 micromol/l) 9. Creatinine phosphokinase (CK) more than three times ULN 10. Uncontrolled hypothyroidism (defined as any elevation of Thyroid-Stimulating Hormone [TSH] above ULN) 11. Participation in another clinical trial concurrently or within 30 days prior to screening for entry into this study (patients may be participating in an observational study such as the British Society for Rheumatology Biologics register) 12. Other serious illness or significant abnormalities that may compromise the patient's safety or successul participation in the study 13. Any illness which, in the doctor's opinion, means that the patient is unable to give informed consent 14. Known alcohol abuse Previous exclusion criteria: 1. Patients who are pregnant or women of child-bearing age not using adequate contraception 2. Known primary muscle disorder 3. Known atherosclerotic disease 4. Known familial hyperlipidamia requiring drug therapy 5. Known diabetes 6. Calculated absolute ten year Cardio-Vascular Disease (CVD) risk of 20% or higher, using the Joint British Societies revised risk calculator 7. Known hypersensitivity or intolerance to statins 8. Active liver disease or hepatic dysfunction with Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) more than two times Upper Limit of Normal (ULN) 9. Severe renal dysfunction (creatinine >150 micromol/l) 10. Creatinine phosphokinase (CK) more than three times ULN 11. Uncontrolled hypothyroidism (defined as any elevation of Thyroid-Stimulating Hormone [TSH] above ULN) 12. Participation in another clinical trial concurrently or within 30 days prior to screening for entry into this study (patients may be participating in an observational study such as the British Society for Rheumatology Biologics register) 13. Other serious illness or significant abnormalities that may compromise the patient's safety or successul participation in the study 14. Any illness which, in the doctor's opinion, means that the patient is unable to give informed consent 15. Known alcohol abuse
Recruitment start date	07/08/2007
Recruitment end date	01/08/2014

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Dudley Group of Hospitals NHS Trust

Dudley
DY1 2HQ
United Kingdom

Sponsor information

University of Manchester (UK)
University/education

University Research Office
Christie Building
Oxford Road
Manchester
M13 9PL
England
United Kingdom

Phone	+44 (0)161 275 2227
Email	karen.shaw@manchester.ac.uk
Website	http://www.manchester.ac.uk
"ROR"	https://ror.org/027m9bs27

Funders

Funder type

Research organisation

British Heart Foundation (UK)
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): the_bhf, The British Heart Foundation, BHF
Location: United Kingdom

Arthritis Research Campaign (ARC) (UK) (ref: 16514)

No information available

Pfizer UK Ltd (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	20/04/2015		Yes	No
Results article	results	01/09/2019	06/02/2020	Yes	No

Editorial Notes

06/02/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.