Arthritis, Rheumatoid, Osteoarthritis
Conditions
Keywords
GI events in high risk GI arthritis patients
Brief summary
To determine whether celecoxib is superior to combined therapy with diclofenac and omeprazole in the incidence of clinically significant upper and/or lower gastrointestinal (GI) events in high GI risk subjects with osteoarthritis and/or rheumatoid arthritis.
Interventions
DRUGCelecoxib
Participants are assigned to one of two groups in parallel for the duration of the study
DRUGDiclofenac + Omeprazole
Participants are assigned to one of two groups in parallel for the duration of the study
Sponsors
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 a clinical diagnosis of OA or RA and who are expected to require regular anti-inflammatory therapy for arthritis symptom management * Subjects must be aged 60 years or older with or without a history of gastroduodenal (GD) ulceration; or be of any age 18 years or older and have had documented evidence of GD ulceration 90 days or more prior to the screening visit
Exclusion criteria
* Active GD ulceration or GD ulceration within 90 days of the screening visit. * Concomitant use of low dose aspirin * Previous MI, stroke or significant vascular disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Clinically Significant Upper and/or Lower Gastrointestinal Events (CSULGIEs) | 6 month treatment duration | CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With CSULGIES or Symptomatic Ulcers (SUs) | 6 month treatment duration | CSULGIE=any of the following: GD hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU. |
| Change From Baseline in Patient's Global Arthritis Assessment at Month 6/Early Termination (ET) | Month 6/Early Termination (ET) | Subjects rated response to question: Considering all the ways the osteoarthritis or rheumatoid arthritis affects you, how are you doing today? using a 1 to 5 grading scale where 1=very good and 5=very poor. |
| Number of Subjects With SUs | 6 month treatment duration | Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU. |
| Number of Subjects With CSULGIEs by History of GD Ulceration | 6 month treatment duration | CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments. |
| Number of Subjects With Moderate to Severe Abdominal Symptoms | 6 month treatment duration | Abdominal symptoms were defined by the Medical Dictionary for Regulatory Activities MedDRA System Organ Class (SOC) 'Gastrointestinal Disorders' and keeping high level group term (HLGT) equal to Gastrointestinal Signs and Symptoms. |
| Number of Subjects Withdrawn Due to GI Adverse Events (AEs) | 6 month treatment duration | GI AEs were defined using MedDRA SOC Gastrointestinal Disorders but excluding the following HLGTs: Benign Neoplasms Gastrointestinal; Dental and Gingival Conditions; Oral Soft Tissue Conditions; Salivary Gland Conditions; and Tongue Conditions. |
| Change From Baseline in Hemoglobin at Month 6/ET | Month 6/ET | — |
| Change From Baseline in Ferretin to Month 6/ET | Month 6/ET | — |
| Change From Baseline in C-Reactive Protein to Month 6/ET | Month 6/ET | — |
| Change From Baseline in Hematocrit at Month 6/ET | Month 6/ET | — |
| Number of Subjects With a Clinically Significant Decrease From Baseline in Hematocrit and/or Hemoglobin | 6 month treatment duration | A clinically significant decrease from baseline was defined as a fall in hematocrit \> = 10 percentage points and/or hemoglobin \> = 2 g/dL. |
| Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | 6 month treatment duration | GGT ULN was 49 international units (IU)/liter (L) for females and 61 IU/L for males, AST ULN was 37 IU/L for females and 39 IU/L for males, and ALT ULN was 43 IU/L for females and 45 IU/L for males. |
| Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | Month 6/ET | — |
| Change From Baseline in Iron Binding Capacity to Month 6/ET | Month 6/ET | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Alive at the Post Trial Interview | 6 months following last dose | Interview occurred via telephone to obtain follow-up mortality and hospitalization information. |
| Number of Subjects Hospitalized in Last 6 Months at the Post Trial Interview | 6 months following last dose | Interview occurred via telephone to obtain follow-up mortality and hospitalization information. |
Countries
Belgium, Brazil, Canada, China, Colombia, Costa Rica, Croatia, Czechia, Ecuador, Estonia, France, Germany, Greece, Guatemala, Hong Kong, India, Latvia, Lithuania, Netherlands, Panama, Peru, Portugal, Russia, Serbia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Celecoxib 200 mg BID plus omeprazole placebo and diclofenac SR placebo | 2,238 |
| Oral Diclofenac Plus Omeprazole Oral diclofenac SR (75 mg BID) plus omeprazole (20 mg QD) and celecoxib placebo. | 2,246 |
| Total | 4,484 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 233 | 305 |
| Overall Study | Death | 2 | 2 |
| Overall Study | Laboratory Abnormality | 9 | 33 |
| Overall Study | Lack of Efficacy | 21 | 26 |
| Overall Study | Lost to Follow-up | 29 | 32 |
| Overall Study | Other | 87 | 76 |
| Overall Study | Randomized But Did Not Receive Treatment | 15 | 9 |
| Overall Study | Withdrawal by Subject | 112 | 142 |
Baseline characteristics
| Characteristic | Celecoxib | Oral Diclofenac Plus Omeprazole | Total |
|---|---|---|---|
| Age, Customized 55 to 59 years | 122 participants | 113 participants | 235 participants |
| Age, Customized < 55 years | 176 participants | 164 participants | 340 participants |
| Age, Customized 60 to 64 years | 721 participants | 742 participants | 1463 participants |
| Age, Customized 65 to 69 years | 623 participants | 618 participants | 1241 participants |
| Age, Customized 70 to 74 years | 361 participants | 390 participants | 751 participants |
| Age, Customized > = 75 years | 235 participants | 219 participants | 454 participants |
| Sex: Female, Male Female | 1848 Participants | 1822 Participants | 3670 Participants |
| Sex: Female, Male Male | 390 Participants | 424 Participants | 814 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 530 / 2,223 | 669 / 2,237 |
| serious Total, serious adverse events | 61 / 2,223 | 61 / 2,237 |
Outcome results
Primary
Number of Subjects With Clinically Significant Upper and/or Lower Gastrointestinal Events (CSULGIEs)
CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments.
Time frame: 6 month treatment duration
Population: Intent-to-Treat (ITT) = included all randomized subjects. n = number of subjects with events confirmed by the committee.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects With Clinically Significant Upper and/or Lower Gastrointestinal Events (CSULGIEs) | 20 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With Clinically Significant Upper and/or Lower Gastrointestinal Events (CSULGIEs) | 81 participants |
p-value: <0.0001Life Table Extension
Secondary
Change From Baseline in C-Reactive Protein to Month 6/ET
Time frame: Month 6/ET
Population: Safety population. Number of participants analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in C-Reactive Protein to Month 6/ET | 0.058 mg/dL | Standard Error 0.032 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in C-Reactive Protein to Month 6/ET | 0.073 mg/dL | Standard Error 0.032 |
p-value: 0.681995% CI: [-0.09, 0.06]ANCOVA
Secondary
Change From Baseline in Ferretin to Month 6/ET
Time frame: Month 6/ET
Population: Safety population. Number of participants analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in Ferretin to Month 6/ET | -3.396 ug/dL | Standard Error 2.224 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Ferretin to Month 6/ET | -1.990 ug/dL | Standard Error 2.228 |
p-value: 0.59295% CI: [-6.55, 3.74]ANCOVA
Secondary
Change From Baseline in Hematocrit at Month 6/ET
Time frame: Month 6/ET
Population: Safety population. Number of Participants Analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in Hematocrit at Month 6/ET | -0.306 percent | Standard Error 0.059 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Hematocrit at Month 6/ET | -1.425 percent | Standard Error 0.059 |
p-value: <0.000195% CI: [0.98, 1.25]ANCOVA
Secondary
Change From Baseline in Hemoglobin at Month 6/ET
Time frame: Month 6/ET
Population: Safety population = all randomized subjects who received at least 1 dose of study medication. Number of Participants Analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in Hemoglobin at Month 6/ET | -0.017 grams (g)/deciliter (dL) | Standard Error 0.019 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Hemoglobin at Month 6/ET | -0.423 grams (g)/deciliter (dL) | Standard Error 0.019 |
p-value: <0.000195% CI: [0.36, 0.45]ANCOVA
Secondary
Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET
Time frame: Month 6/ET
Population: Safety population. Number of participants analyzed = number of subjects with analyzable data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Celecoxib | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | GGT | -2.689 IU/L | Standard Error 0.591 |
| Celecoxib | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | AST | -0.901 IU/L | Standard Error 0.239 |
| Celecoxib | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | ALT | -1.151 IU/L | Standard Error 0.364 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | GGT | 7.455 IU/L | Standard Error 0.592 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | AST | 1.490 IU/L | Standard Error 0.239 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Hepatic Measures of GGT, AST or ALT to Month 6/ET | ALT | 5.213 IU/L | Standard Error 0.364 |
Comparison: GGTp-value: <0.000195% CI: [-11.51, -8.78]ANCOVA
Comparison: ASTp-value: <0.000195% CI: [-2.94, -1.84]ANCOVA
Comparison: ALTp-value: <0.000195% CI: [-7.2, -5.52]ANCOVA
Secondary
Change From Baseline in Iron Binding Capacity to Month 6/ET
Time frame: Month 6/ET
Population: Safety population. Number of participants analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in Iron Binding Capacity to Month 6/ET | 2.517 microgram (ug)/dL | Standard Error 1.158 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Iron Binding Capacity to Month 6/ET | 1.952 microgram (ug)/dL | Standard Error 1.161 |
p-value: 0.679595% CI: [-2.11, 3.24]ANCOVA
Secondary
Change From Baseline in Patient's Global Arthritis Assessment at Month 6/Early Termination (ET)
Subjects rated response to question: Considering all the ways the osteoarthritis or rheumatoid arthritis affects you, how are you doing today? using a 1 to 5 grading scale where 1=very good and 5=very poor.
Time frame: Month 6/Early Termination (ET)
Population: ITT. Number of Participants Analyzed = number of subjects with data available for the analysis. Last Observation Carried Forward (LOCF) method was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Celecoxib | Change From Baseline in Patient's Global Arthritis Assessment at Month 6/Early Termination (ET) | 0.754 scores on a scale | Standard Error 0.02 |
| Oral Diclofenac Plus Omeprazole | Change From Baseline in Patient's Global Arthritis Assessment at Month 6/Early Termination (ET) | 0.773 scores on a scale | Standard Error 0.019 |
p-value: 0.414695% CI: [-0.06, 0.03]ANCOVA
Secondary
Number of Subjects With a Clinically Significant Decrease From Baseline in Hematocrit and/or Hemoglobin
A clinically significant decrease from baseline was defined as a fall in hematocrit \> = 10 percentage points and/or hemoglobin \> = 2 g/dL.
Time frame: 6 month treatment duration
Population: Safety population. Number of Participants Analyzed = number of subjects with analyzable data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects With a Clinically Significant Decrease From Baseline in Hematocrit and/or Hemoglobin | 45 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With a Clinically Significant Decrease From Baseline in Hematocrit and/or Hemoglobin | 123 participants |
p-value: <0.000195% CI: [1.96, 3.84]Cochran-Mantel-Haenszel
Secondary
Number of Subjects With CSULGIEs by History of GD Ulceration
CSULGIE=any of the following: gastroduodenal (GD) hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects were assessed by an independent GI Events Adjudication Committee, who were blinded to study treatment assignments.
Time frame: 6 month treatment duration
Population: ITT. n = number of subjects who had history or no history of GD ulceration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | Number of Subjects With CSULGIEs by History of GD Ulceration | History of GD Ulceration (n=395, 400) | 7 participants |
| Celecoxib | Number of Subjects With CSULGIEs by History of GD Ulceration | No History of GD Ulceration (n=1843, 1846) | 13 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With CSULGIEs by History of GD Ulceration | History of GD Ulceration (n=395, 400) | 13 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With CSULGIEs by History of GD Ulceration | No History of GD Ulceration (n=1843, 1846) | 68 participants |
Secondary
Number of Subjects With CSULGIES or Symptomatic Ulcers (SUs)
CSULGIE=any of the following: GD hemorrhage; gastric outlet obstruction; GD, small or large bowel perforation; small or large bowel hemorrhage; clinically significant anemia of defined GI origin; acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage; clinically significant anemia of presumed occult GI origin including possible small bowel blood loss. Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU.
Time frame: 6 month treatment duration
Population: ITT. n = number of subjects with CSULGIEs or SUs as confirmed by the committee.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects With CSULGIES or Symptomatic Ulcers (SUs) | 25 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With CSULGIES or Symptomatic Ulcers (SUs) | 92 participants |
p-value: <0.0001Life Table Extension
Secondary
Number of Subjects Withdrawn Due to GI Adverse Events (AEs)
GI AEs were defined using MedDRA SOC Gastrointestinal Disorders but excluding the following HLGTs: Benign Neoplasms Gastrointestinal; Dental and Gingival Conditions; Oral Soft Tissue Conditions; Salivary Gland Conditions; and Tongue Conditions.
Time frame: 6 month treatment duration
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects Withdrawn Due to GI Adverse Events (AEs) | 114 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects Withdrawn Due to GI Adverse Events (AEs) | 167 participants |
p-value: 0.0006Life Table Extension
Secondary
Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN)
GGT ULN was 49 international units (IU)/liter (L) for females and 61 IU/L for males, AST ULN was 37 IU/L for females and 39 IU/L for males, and ALT ULN was 43 IU/L for females and 45 IU/L for males.
Time frame: 6 month treatment duration
Population: Safety population. Number of participants analyzed = number of subjects with analyzable data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Celecoxib | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | GGT | 26 participants |
| Celecoxib | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | AST | 8 participants |
| Celecoxib | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | ALT | 13 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | GGT | 86 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | AST | 12 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With Hepatic AEs in Gamma Glutamyl-Transferase (GGT), Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) of 3 Times the Upper Limit of Normal (ULN) | ALT | 27 participants |
Comparison: GGTp-value: <0.000195% CI: [2.156, 5.141]Fisher Exact
Comparison: ASTp-value: 0.380995% CI: [0.618, 3.684]Fisher Exact
Comparison: ALTp-value: 0.026495% CI: [1.081, 4.038]Fisher Exact
Secondary
Number of Subjects With Moderate to Severe Abdominal Symptoms
Abdominal symptoms were defined by the Medical Dictionary for Regulatory Activities MedDRA System Organ Class (SOC) 'Gastrointestinal Disorders' and keeping high level group term (HLGT) equal to Gastrointestinal Signs and Symptoms.
Time frame: 6 month treatment duration
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects With Moderate to Severe Abdominal Symptoms | 132 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With Moderate to Severe Abdominal Symptoms | 162 participants |
p-value: 0.0495Life Table Extension
Secondary
Number of Subjects With SUs
Subjects with evaluation at an event visit and found to have an ulcer on endoscopy, but did not meet any criteria considered for the primary endpoint by the GI committee were designated as having an SU.
Time frame: 6 month treatment duration
Population: ITT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects With SUs | 5 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects With SUs | 11 participants |
p-value: 0.1132Life Table Extension
Other Pre-specified
Number of Subjects Alive at the Post Trial Interview
Interview occurred via telephone to obtain follow-up mortality and hospitalization information.
Time frame: 6 months following last dose
Population: Safety population. Number of participants analyzed = number of subjects with follow-up information available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects Alive at the Post Trial Interview | 2018 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects Alive at the Post Trial Interview | 2023 participants |
Other Pre-specified
Number of Subjects Hospitalized in Last 6 Months at the Post Trial Interview
Interview occurred via telephone to obtain follow-up mortality and hospitalization information.
Time frame: 6 months following last dose
Population: Safety population. Number of participants analyzed = number of subjects with follow-up information available.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Celecoxib | Number of Subjects Hospitalized in Last 6 Months at the Post Trial Interview | 82 participants |
| Oral Diclofenac Plus Omeprazole | Number of Subjects Hospitalized in Last 6 Months at the Post Trial Interview | 79 participants |