Clinical trial NCT00447759: The Standard Care Versus Celecoxib Outcome Trial
Official title: Phase 4 Study A Large Streamline Safety Study Designed to Compare the Cardiovascular Safety od Celecoxib Versus Traditional Non-selective NSAID's
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis
Rheumatoid Arthritis
Keywords: Celecoxib
Celebrex
Ibuprofen
Diclofenac
NSAID
Osteoarthritis
Rheumatoid Arthritis
Arthritis
Safety study
Cardiovascular safety
Clinical trial
PROBE design
University of Dundee
Medicines Monitoring Unit
MEMO
Professor Tom MacDonald
Lead sponsor: University of Dundee
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: University of Nottingham
First posted: 2007-03-15
Enrollment: 7297
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective Randomised Open Blinded-Endpoint Study (PROBE)
Primary purpose: TREATMENT

Brief summary: The Standard Care versus Celecoxib Outcome Trial (SCOT) is a large streamline safety study designed to compare the cardiovascular safety of celecoxib versus traditional non-selective Non Steroidal Anti-Inflammatory Drug (NSAID) therapy.Traditional NSAID's are associated with significant morbidity and mortality from gastrointestinal toxicity. Cyclooxygenase 2 (Cox-2)selective agents are associated with reduced upper gastrointestinal toxicity.Traditional NSAID's and Cox-2 inhibitors may also be associated with cardiovascular and renal disorders. Data from both randomised and observational studies suggest that celecoxib has similar or reduced cardiovascular toxicity when compared to traditional NSAID's. However, the overall safety balance of a strategy of celecoxib therapy versus a strategy of NSAID therapy is unknown. The European Medicines Evaluation Agency (EMEA) has requested that studies of the cardiovascular safety of celecoxib be carried out within the indicated population of Europe. This study addresses these issues by comparing the cardiovascular safety of celecoxib therapy with traditional NSAID therapy in the setting of the EU healthcare system.

As of May 2013, 7300 patients had been randomised, and had accrued an average 4.2 years of follow up by the end of May 2014.

Detailed description: Aims

The present proposal seeks to compare the cardiovascular and gastrointestinal safety and effectiveness of a strategy of initial randomisation to treatment with the selective COX-2 inhibitor celecoxib or to 'usual-care' with their current non-selective NSAID therapy (with or without cyto-protection with ulcer healing drug use in either celecoxib or 'usual-care' limbs).

Trial Design

This trial utilises the Prospective Randomised Open Blinded End point (PROBE) design . Patients with clinically diagnosed osteoarthritis (OA) or rheumatoid arthritis (RA) 60 years of age or more who are free from established cardiovascular disease and who require chronic NSAID therapy will be identified in the setting of primary care. Patients will be randomised to receive either celecoxib or to continue their previous standard NSAID therapy. They will then be followed up for an average of 4.2 years in the setting of the local National Healthcare system. The study will terminate when 277 adjudicated cardiovascular events have accrued. A summary is shown in the diagram below.

Eligibility criteria: Inclusion Criteria:

* Subjects 60 years or over Male \& Female
* Chronic NSAIDs use for 90 days or more in a 12 month period
* Subjects who have a licensed indication for chronic non-selective NSAID or Celecoxib.
* Eligible for treatment with either Celecoxib or alternative traditional non-selective NSAID.
* Subjects who are willing to consent to their paper and electronic medical records and prescribing data to be accessed.
* Subjects who are willing to be contacted and interviewed by trial investigators.

Exclusion Criteria:

* Established cardiovascular disease including ischaemic heart disease, Myocardial Infarction, angina or acute coronary syndrome, cerebrovascular disease or cerebrovascular accident or transient ischaemic attack, established peripheral vascular disease and moderate to severe heart failure.

Primary outcomes:
measure: compare cardiovascular safety of celecoxib and traditional NSAIDs prescribed for the treatment of arthritis.
timeFrame: 4 years
Secondary outcomes:
measure: demonstrate the superiority of celecoxib over traditional NSAIDs on ulcer-related upper gastrointestinal complications.
timeFrame: 4 years
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: University of Southern Denmark
city: Zeist
country: Netherlands
facility: Julius Clinical Research
city: Aberdeen
country: United Kingdom
facility: University of Aberdeen
city: Birmingham
country: United Kingdom
facility: University of Birmingham
city: Dundee
country: United Kingdom
facility: University of Dundee
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh
city: Glasgow
country: United Kingdom
facility: University of Glasgow
city: Inverness
country: United Kingdom
facility: NHS Highlands
city: Nottingham
country: United Kingdom
facility: University of Nottingham
city: Oxford
country: United Kingdom
facility: University of Oxford
Study officials:
affiliation: University of Dundee
name: Thomas M MacDonald, MD MRCP FRCP
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Glasgow
name: Ian Ford, FRCP FRSE
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Nottingham
name: Christopher J Hawkey, MRCP DM FRC
role: PRINCIPAL_INVESTIGATOR
References:
citation: MacDonald TM. A European's perspective of COX-2 drug safety. J Cardiovasc Pharmacol. 2006;47 Suppl 1:S92-7. doi: 10.1097/00005344-200605001-00017.
citation: MacDonald TM, Hawkey CJ, Ford I, McMurray JJV, Scheiman JM, Hallas J, Findlay E, Grobbee DE, Hobbs FDR, Ralston SH, Reid DM, Walters MR, Webster J, Ruschitzka F, Ritchie LD, Perez-Gutthann S, Connolly E, Greenlaw N, Wilson A, Wei L, Mackenzie IS. Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT). Eur Heart J. 2017 Jun 14;38(23):1843-1850. doi: 10.1093/eurheartj/ehw387.
citation: Jennings CG, MacDonald TM, Wei L, Brown MJ, McConnachie L, Mackenzie IS. Does offering an incentive payment improve recruitment to clinical trials and increase the proportion of socially deprived and elderly participants? Trials. 2015 Mar 7;16:80. doi: 10.1186/s13063-015-0582-8.
citation: Macdonald TM, Mackenzie IS, Wei L, Hawkey CJ, Ford I; SCOT study group collaborators. Methodology of a large prospective, randomised, open, blinded endpoint streamlined safety study of celecoxib versus traditional non-steroidal anti-inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis: protocol of the standard care versus celecoxib outcome trial (SCOT). BMJ Open. 2013 Jan 29;3(1):e002295. doi: 10.1136/bmjopen-2012-002295.