Arthritis, Rheumatoid
Conditions
Brief summary
To answer the question of overall benefit: risk of celecoxib when compared to two most commonly prescribe traditional (non-selective) nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of arthritis pain. For this purpose, patients with osteoarthritis or rheumatoid arthritis with or at risk of developing cardiovascular disease will be recruited. The cardiovascular, gastrointestinal and renal safety and symptomatic benefit in each treatment group will be assessed accordingly.
Interventions
DRUGcelecoxib
100 to 200 mg twice daily, taken by mouth
DRUGIbuprofen
ibuprofen 600 mg to 800 mg three times daily, taken by mouth
DRUGNaproxen
naproxen 375mg to 500 mg twice daily, taken by mouth
Sponsors
The Cleveland Clinic
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with osteoarthritis or rheumatoid Arthritis with or at risk of developing cardiovascular disease and who require and eligible for chronic, daily therapy with an NSAID to control arthritis sign and symptoms.
Exclusion criteria
* Subjects have had a recent cardiovascular event, unstable cardiovascular conditions, or any major surgery (cardiac or non-cardiac) within 3 months prior to randomization; * Subjects with medical or laboratory abnormality that would make the subject inappropriate for entry into this trial * Subjects require treatment with aspirin \> 325 mg /day * Subjects with known hypersensitivity to celecoxib, ibuprofen, naproxen, aspirin or esomeprazole, etc.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | Intent to Treat (ITT) Population - 30 months; Modified ITT (MITT) Population - 42 months | APTC events are defined as a composite of any of the following events: Death due to CV causes (including cardiac, cerebrovascular, venous thromboembolic, haemorrhagic, other vascular, or unknown cause); Non-fatal MI; Non-fatal stroke (including intracranial hemorrhages, stroke of ischemic or unknown etiology). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | ITT Population - 30 months; MITT Population - 42 months | MACE defined as the composite of CV death (including hemorrhagic death), non-fatal MI, non-fatal stroke, hospitalization for UA, revascularization or hospitalization for TIA |
| The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | ITT Population - 30 months; MITT Population - 42 months | CSGIE include: Gastroduodenal (GD) hemorrhage, Gastric outlet obstruction, Gastroduodenal, small bowel or large bowel perforation, Large bowel hemorrhage, Small bowel hemorrhage, Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage, Symptomatic gastric or duodenal ulcer |
| Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | ITT and MITT Population - Baseline to 42 months | VAS question How much pain do you have was graded on a scale from 0 to 100 with 0 indicating No pain and 100 indicating Worst possible pain. |
Countries
Australia, Brazil, Canada, Colombia, Costa Rica, Hong Kong, Mexico, Panama, Peru, Philippines, Taiwan, Ukraine, United States
Participant flow
Recruitment details
The study was conducted at 950 centers in Australia (11), Brazil (30), Canada (64), Colombia (7), Costa Rica (12), Hong Kong (4), Mexico (11), Panama (2), Peru (5), Philippines (8), Taiwan (10), Ukraine 19), and United States (767); a total of 24 sites were activated but did not randomized any subject.
Pre-assignment details
All eligible participants were enrolled in to the study.
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib Celecoxib 100-200 mg twice daily with placebo to match ibuprofen 600-800 mg thrice daily and placebo to match naproxen 375-500 mg twice daily | 8,072 |
| Ibuprofen Ibuprofen 600-800 mg thrice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match naproxen 375-500 mg twice daily | 8,040 |
| Naproxen Naproxen 375-500 mg twice daily with placebo to match celecoxib 100-200 mg twice daily and placebo to match ibuprofen 600-800 mg thrice daily. | 7,969 |
| Total | 24,081 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 189 | 192 | 228 |
| Overall Study | Does not meet entrance criteria | 13 | 10 | 8 |
| Overall Study | Lost to Follow-up | 611 | 588 | 542 |
| Overall Study | Missing Subject Summary Status | 62 | 61 | 62 |
| Overall Study | No longer willing to participate | 600 | 606 | 585 |
| Overall Study | Other | 181 | 231 | 205 |
| Overall Study | Physician Decision | 80 | 76 | 59 |
| Overall Study | Study terminated by sponsor | 11 | 4 | 8 |
| Overall Study | Withdrawal by Subject | 661 | 692 | 651 |
Baseline characteristics
| Characteristic | Celecoxib | Ibuprofen | Naproxen | Total |
|---|---|---|---|---|
| Age, Continuous | 63.0 Years STANDARD_DEVIATION 9.5 | 63.2 Years STANDARD_DEVIATION 9.4 | 63.3 Years STANDARD_DEVIATION 9.4 | 63.2 Years STANDARD_DEVIATION 9.4 |
| Sex: Female, Male Female | 5175 Participants | 5174 Participants | 5096 Participants | 15445 Participants |
| Sex: Female, Male Male | 2897 Participants | 2866 Participants | 2873 Participants | 8636 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 4,268 / 8,030 | 4,363 / 7,992 | 4,337 / 7,933 |
| serious Total, serious adverse events | 1,473 / 8,030 | 1,624 / 7,992 | 1,611 / 7,933 |
Outcome results
Primary
The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC).
APTC events are defined as a composite of any of the following events: Death due to CV causes (including cardiac, cerebrovascular, venous thromboembolic, haemorrhagic, other vascular, or unknown cause); Non-fatal MI; Non-fatal stroke (including intracranial hemorrhages, stroke of ischemic or unknown etiology).
Time frame: Intent to Treat (ITT) Population - 30 months; Modified ITT (MITT) Population - 42 months
Population: ITT - The ITT population will consist of all subjects randomized for participation in the study.~MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | ITT (N = 8072, 8040, 7969) | 2.3 Percentage of Partcipants |
| Celecoxib | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | MITT (N = 8030, 7990, 7933) | 1.7 Percentage of Partcipants |
| Ibuprofen | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | ITT (N = 8072, 8040, 7969) | 2.7 Percentage of Partcipants |
| Ibuprofen | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | MITT (N = 8030, 7990, 7933) | 1.9 Percentage of Partcipants |
| Naproxen | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | ITT (N = 8072, 8040, 7969) | 2.5 Percentage of Partcipants |
| Naproxen | The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | MITT (N = 8030, 7990, 7933) | 1.8 Percentage of Partcipants |
Comparison: ITT Populationp-value: 0.000295% CI: [0.76, 1.13]Regression, Cox
Comparison: MITT Populationp-value: 0.000195% CI: [0.72, 1.14]Regression, Cox
Comparison: ITT Populationp-value: <0.000195% CI: [0.7, 1.04]Regression, Cox
Comparison: MITT Populationp-value: <0.000195% CI: [0.64, 1.02]Regression, Cox
Comparison: ITT Populationp-value: 0.018295% CI: [0.89, 1.31]Regression, Cox
Comparison: MITT Populationp-value: 0.02595% CI: [0.89, 1.4]Regression, Cox
Secondary
Change From Baseline in Patient's Assessment of Arthritis Pain (VAS)
VAS question How much pain do you have was graded on a scale from 0 to 100 with 0 indicating No pain and 100 indicating Worst possible pain.
Time frame: ITT and MITT Population - Baseline to 42 months
Population: ITT - The ITT population will consist of all subjects randomized for participation in the study.~MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 MITT N=6224, 6128, 6155 | -11.7 Number of participants | Standard Deviation 28.93 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 (ITT) N=5792, 5696, 5846 | -11.0 Number of participants | Standard Deviation 29.15 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 MITT N=4815, 4769, 4782 | -11.4 Number of participants | Standard Deviation 29.44 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 MITT N=6772, 6686, 6732 | -11.4 Number of participants | Standard Deviation 27.7 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 (ITT) N=5310, 5181. 5246 | -11.3 Number of participants | Standard Deviation 29.11 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 (ITT) N=4818, 4776, 4785 | -11.3 Number of participants | Standard Deviation 29.44 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 MITT N=7170, 7078, 7142 | -10.5 Number of participants | Standard Deviation 26.38 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 (ITT) N=3692, 3627, 3635 | -10.1 Number of participants | Standard Deviation 29.61 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 MITT N=3691, 3623, 3635 | -10.2 Number of participants | Standard Deviation 29.61 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 MITT N=7372, 7367, 7321 | -8.2 Number of participants | Standard Deviation 24.69 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 (ITT) N=3469, 3406, 3439 | -11.4 Number of participants | Standard Deviation 29.78 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 MITT N=5305, 5175, 5242 | -11.3 Number of participants | Standard Deviation 29.11 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (MITT) N=7974, 7954, 7894 | 54.0 Number of participants | Standard Deviation 23.53 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 (ITT) N=4140, 4069, 4086 | -10.5 Number of participants | Standard Deviation 29.81 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 (ITT) N=7382, 7379, 7325 | -8.2 Number of participants | Standard Deviation 24.69 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (ITT) N= 8014, 8001, 7928 | 54.0 Number of participants | Standard Deviation 23.53 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 (ITT) N=7180, 7090, 7149 | -10.5 Number of participants | Standard Deviation 26.39 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 MITT N=4139, 4067, 4085 | -10.5 Number of participants | Standard Deviation 29.81 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 MITT N=5787, 5689, 5844 | -11.0 Number of participants | Standard Deviation 29.16 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 (ITT) N=6777, 6696, 6740 | -11.4 Number of participants | Standard Deviation 27.7 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 (ITT) N=6230, 6137, 6159 | -11.7 Number of participants | Standard Deviation 28.92 |
| Celecoxib | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 MITT N=3468, 3404, 3438 | -11.4 Number of participants | Standard Deviation 29.78 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 MITT N=5787, 5689, 5844 | -11.6 Number of participants | Standard Deviation 29.3 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (ITT) N= 8014, 8001, 7928 | 54.1 Number of participants | Standard Deviation 23.58 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 (ITT) N=7382, 7379, 7325 | -9.0 Number of participants | Standard Deviation 25.69 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 (ITT) N=6777, 6696, 6740 | -11.7 Number of participants | Standard Deviation 28.1 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 (ITT) N=5310, 5181. 5246 | -11.3 Number of participants | Standard Deviation 29.1 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 (ITT) N=4818, 4776, 4785 | -11.5 Number of participants | Standard Deviation 28.98 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (MITT) N=7974, 7954, 7894 | 54.1 Number of participants | Standard Deviation 23.58 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 (ITT) N=7180, 7090, 7149 | -10.6 Number of participants | Standard Deviation 26.92 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 (ITT) N=6230, 6137, 6159 | -12.1 Number of participants | Standard Deviation 28.97 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 (ITT) N=5792, 5696, 5846 | -11.6 Number of participants | Standard Deviation 29.29 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 (ITT) N=4140, 4069, 4086 | -11.2 Number of participants | Standard Deviation 29.71 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 (ITT) N=3692, 3627, 3635 | -10.7 Number of participants | Standard Deviation 29.62 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 (ITT) N=3469, 3406, 3439 | -11.1 Number of participants | Standard Deviation 30.14 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 MITT N=7372, 7367, 7321 | -9.0 Number of participants | Standard Deviation 25.67 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 MITT N=7170, 7078, 7142 | -10.6 Number of participants | Standard Deviation 26.92 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 MITT N=6772, 6686, 6732 | -11.7 Number of participants | Standard Deviation 28.1 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 MITT N=6224, 6128, 6155 | -12.1 Number of participants | Standard Deviation 28.97 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 MITT N=5305, 5175, 5242 | -11.3 Number of participants | Standard Deviation 29.12 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 MITT N=4815, 4769, 4782 | -11.5 Number of participants | Standard Deviation 29 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 MITT N=4139, 4067, 4085 | -11.2 Number of participants | Standard Deviation 29.71 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 MITT N=3691, 3623, 3635 | -10.7 Number of participants | Standard Deviation 29.62 |
| Ibuprofen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 MITT N=3468, 3404, 3438 | -11.1 Number of participants | Standard Deviation 30.14 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 MITT N=6772, 6686, 6732 | -12.3 Number of participants | Standard Deviation 27.81 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 (ITT) N=6230, 6137, 6159 | -12.1 Number of participants | Standard Deviation 28.83 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 (ITT) N=7382, 7379, 7325 | -9.9 Number of participants | Standard Deviation 25.53 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon8 MITT N=6224, 6128, 6155 | -12.1 Number of participants | Standard Deviation 28.84 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 (ITT) N=7180, 7090, 7149 | -11.1 Number of participants | Standard Deviation 26.83 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (MITT) N=7974, 7954, 7894 | 54.1 Number of participants | Standard Deviation 24.02 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 MITT N=5787, 5689, 5844 | -11.9 Number of participants | Standard Deviation 29.3 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 (ITT) N=4818, 4776, 4785 | -11.4 Number of participants | Standard Deviation 29.27 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 MITT N=3468, 3404, 3438 | -12.1 Number of participants | Standard Deviation 30.27 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 MITT N=5305, 5175, 5242 | -11.7 Number of participants | Standard Deviation 29.33 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon18 (ITT) N=5310, 5181. 5246 | -11.7 Number of participants | Standard Deviation 29.33 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 MITT N=3691, 3623, 3635 | -11.6 Number of participants | Standard Deviation 29.8 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon24 MITT N=4815, 4769, 4782 | -11.3 Number of participants | Standard Deviation 29.26 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon42 (ITT) N=3469, 3406, 3439 | -12.1 Number of participants | Standard Deviation 30.27 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon36 (ITT) N=3692, 3627, 3635 | -11.6 Number of participants | Standard Deviation 29.8 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon4 (ITT) N=6777, 6696, 6740 | -12.3 Number of participants | Standard Deviation 27.8 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon1 MITT N=7372, 7367, 7321 | -9.9 Number of participants | Standard Deviation 25.53 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 (ITT) N=4140, 4069, 4086 | -11.3 Number of participants | Standard Deviation 29.71 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Baseline (ITT) N= 8014, 8001, 7928 | 54.1 Number of participants | Standard Deviation 24.04 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon2 MITT N=7170, 7078, 7142 | -11.1 Number of participants | Standard Deviation 26.84 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon12 (ITT) N=5792, 5696, 5846 | -11.9 Number of participants | Standard Deviation 29.3 |
| Naproxen | Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | Change-Baseline to Mon30 MITT N=4139, 4067, 4085 | -11.3 Number of participants | Standard Deviation 29.7 |
Comparison: Change from baseline to Month 1 (ITT)p-value: <0.000195% CI: [1.01, 2.53]Mixed Models Analysis
Comparison: Change from baseline to Month 1 (ITT)p-value: 0.037395% CI: [0.05, 1.56]Mixed Models Analysis
Comparison: Change from baseline to Month 1 (ITT)p-value: 0.012995% CI: [0.2, 1.72]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (ITT)p-value: 0.18395% CI: [-0.25, 1.29]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (ITT)p-value: 0.777795% CI: [-0.88, 0.66]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (ITT)p-value: 0.107295% CI: [-0.14, 1.4]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (ITT)p-value: 0.823795% CI: [-0.12, 1.46]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (ITT)p-value: 0.823795% CI: [-0.88, 0.7]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (ITT)p-value: 0.058795% CI: [-0.03, 1.55]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (ITT)p-value: 0.312995% CI: [-0.39, 1.23]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (ITT)p-value: 0.652695% CI: [-0.63, 1]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (ITT)p-value: 0.577495% CI: [-0.58, 1.05]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (ITT)p-value: 0.063295% CI: [-0.04, 1.62]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (ITT)p-value: 0.45495% CI: [-0.52, 1.15]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (ITT)p-value: 0.270595% CI: [-0.37, 1.3]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (ITT)p-value: 0.522595% CI: [-0.58, 1.14]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (ITT)p-value: 0.599695% CI: [-1.1, 0.63]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (ITT)p-value: 0.246195% CI: [-0.35, 1.38]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (ITT)p-value: 0.812795% CI: [-0.79, 1]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (ITT)p-value: 0.964195% CI: [-0.92, 0.87]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (ITT)p-value: 0.778495% CI: [-0.77, 1.03]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (ITT)p-value: 0.210595% CI: [-0.34, 1.56]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (ITT)p-value: 0.290995% CI: [-0.44, 1.46]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (ITT)p-value: 0.845995% CI: [-0.86, 1.05]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (ITT)p-value: 0.111695% CI: [-0.19, 1.8]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (ITT)p-value: 0.975195% CI: [-0.98, 1.01]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (ITT)p-value: 0.120295% CI: [-0.21, 1.79]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (ITT)p-value: 0.376795% CI: [-0.56, 1.48]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (ITT)p-value: 0.112395% CI: [-1.85, 0.19]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (ITT)p-value: 0.013795% CI: [0.26, 2.31]Mixed Models Analysis
Comparison: Change from Baseline to Month 1 (MITT)p-value: <0.000195% CI: [1.07, 2.47]Mixed Models Analysis
Comparison: Change from Baseline to Month 1 (MITT)p-value: 0.019795% CI: [0.13, 1.54]Mixed Models Analysis
Comparison: Change from Baseline to Month 1 (MITT)p-value: 0.009495% CI: [0.23, 1.64]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (MITT)p-value: 0.124795% CI: [-0.16, 1.31]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (MITT)p-value: 0.827895% CI: [-0.81, 0.65]Mixed Models Analysis
Comparison: Change from baseline to Month 2 (MITT)p-value: 0.080295% CI: [-0.08, 1.39]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (MITT)p-value: 0.082295% CI: [-0.09, 1.46]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (MITT)p-value: 0.831495% CI: [-0.86, 0.69]Mixed Models Analysis
Comparison: Change from baseline to Month 4 (MITT)p-value: 0.051695% CI: [-0.01, 1.54]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (MITT)p-value: 0.320295% CI: [-0.4, 1.24]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (MITT)p-value: 0.589395% CI: [-0.6, 1.05]Mixed Models Analysis
Comparison: Change from baseline to Month 8 (MITT)p-value: 0.65195% CI: [-0.63, 1.01]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (MITT)p-value: 0.079695% CI: [-0.09, 1.62]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (MITT)p-value: 0.506195% CI: [-0.57, 1.15]Mixed Models Analysis
Comparison: Change from baseline to Month 12 (MITT)p-value: 0.279695% CI: [-0.38, 1.33]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (MITT)p-value: 0.672595% CI: [-0.69, 1.08]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (MITT)p-value: 0.638195% CI: [-1.1, 0.67]Mixed Models Analysis
Comparison: Change from baseline to Month 18 (MITT)p-value: 0.373795% CI: [-0.49, 1.29]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (MITT)p-value: 0.913995% CI: [-0.87, 0.97]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (MITT)p-value: 0.999895% CI: [-0.92, 0.92]Mixed Models Analysis
Comparison: Change from baseline to Month 24 (MITT)p-value: 0.914495% CI: [-0.88, 0.98]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (MITT)p-value: 0.22595% CI: [-0.38, 1.61]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (MITT)p-value: 0.275895% CI: [-0.44, 1.55]Mixed Models Analysis
Comparison: Change from baseline to Month 30 (MITT)p-value: 0.90395% CI: [-0.94, 1.06]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (MITT)p-value: 0.09195% CI: [-0.14, 1.94]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (MITT)p-value: 0.766895% CI: [-0.88, 1.2]Mixed Models Analysis
Comparison: Change from baseline to Month 36 (MITT)p-value: 0.165395% CI: [-0.31, 1.78]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (MITT)p-value: 0.432395% CI: [-0.65, 1.52]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (MITT)p-value: 0.143995% CI: [-1.89, 0.28]Mixed Models Analysis
Comparison: Change from baseline to Month 42 (MITT)p-value: 0.025195% CI: [0.16, 2.33]Mixed Models Analysis
Secondary
The First Occurrence of a Major Adverse Cardiovascular Events (MACE)
MACE defined as the composite of CV death (including hemorrhagic death), non-fatal MI, non-fatal stroke, hospitalization for UA, revascularization or hospitalization for TIA
Time frame: ITT Population - 30 months; MITT Population - 42 months
Population: ITT - The ITT population will consist of all subjects randomized for participation in the study.~MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | ITT (N = 8072, 8040, 7969) | 4.2 Percentage of Participants |
| Celecoxib | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | MITT (N = 8030, 7990, 7933) | 3.1 Percentage of Participants |
| Ibuprofen | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | ITT (N = 8072, 8040, 7969) | 4.8 Percentage of Participants |
| Ibuprofen | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | MITT (N = 8030, 7990, 7933) | 3.6 Percentage of Participants |
| Naproxen | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | ITT (N = 8072, 8040, 7969) | 4.3 Percentage of Participants |
| Naproxen | The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | MITT (N = 8030, 7990, 7933) | 3.2 Percentage of Participants |
Comparison: ITT Populationp-value: 0.642795% CI: [0.83, 1.12]Regression, Cox
Comparison: ITT Populationp-value: 0.059795% CI: [0.75, 1.01]Regression, Cox
Comparison: ITT Populationp-value: 0.148195% CI: [0.96, 1.29]Regression, Cox
Comparison: MITT Populationp-value: 0.575895% CI: [0.8, 1.13]Regression, Cox
Comparison: MITT Populationp-value: 0.020495% CI: [0.69, 0.97]Regression, Cox
Comparison: MITT Populationp-value: 0.075195% CI: [0.98, 1.38]Regression, Cox
Secondary
The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE)
CSGIE include: Gastroduodenal (GD) hemorrhage, Gastric outlet obstruction, Gastroduodenal, small bowel or large bowel perforation, Large bowel hemorrhage, Small bowel hemorrhage, Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage, Symptomatic gastric or duodenal ulcer
Time frame: ITT Population - 30 months; MITT Population - 42 months
Population: ITT - The ITT population will consist of all subjects randomized for participation in the study.~MITT - The MITT analysis population consisted of all randomized subjects who had received at least one dose of study drug, and contributed at least one post-baseline visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | ITT (N = 8072, 8040, 7969) | 0.7 Percentage of Participants |
| Celecoxib | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | MITT (N = 8030, 7990, 7933) | 0.3 Percentage of Participants |
| Ibuprofen | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | ITT (N = 8072, 8040, 7969) | 0.9 Percentage of Participants |
| Ibuprofen | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | MITT (N = 8030, 7990, 7933) | 0.7 Percentage of Participants |
| Naproxen | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | ITT (N = 8072, 8040, 7969) | 0.7 Percentage of Participants |
| Naproxen | The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | MITT (N = 8030, 7990, 7933) | 0.7 Percentage of Participants |
Comparison: ITT Populationp-value: 0.857695% CI: [0.67, 1.4]Regression, Cox
Comparison: ITT Populationp-value: 0.120295% CI: [0.53, 1.08]Regression, Cox
Comparison: ITT Populationp-value: 0.173495% CI: [0.9, 1.81]Regression, Cox
Comparison: MITT Populationp-value: 0.004195% CI: [0.32, 0.81]Regression, Cox
Comparison: MITT Populationp-value: 0.000395% CI: [0.27, 0.68]Regression, Cox
Comparison: MITT Populationp-value: 0.424395% CI: [0.8, 1.69]Regression, Cox