Rheumatoid Arthritis
Conditions
Keywords
Methotrexate (MTX), Ticagrelor
Brief summary
This is an open label study to assess the improvement in the Disease Activity Score for 28-joint counts (DAS28) with ticagrelor given at 90 mg twice daily in patients with RA who have active disease despite MTX therapy (as defined by the inclusion/exclusion criteria). There will also be a cross sectional analysis of baseline platelet activity in subjects with rheumatoid arthritis and osteoarthritis. Subjects in the OA cohort will not receive any study medication, and will only have one study visit. Patients will receive 90 mg ticagrelor orally bid. The patients will receive drug for 30-days. Methotrexate dose will remain stable throughout the study duration.
Detailed description
The two main goals of this study are to demonstrate the heightened cardiovascular risk in RA by comparing platelet activity, inflammation and endothelial function in baseline rheumatoid arthritis versus age- and sex-matched patients with osteoarthritis; and 2) to demonstrate the effect of ticagrelor in rheumatoid arthritis by the pre- and post- measures of clinical RA severity, platelet activity, inflammation and endothelial function in rheumatoid arthritis before and after ticagrelor therapy.
Interventions
DRUGTicagrelor
DRUGMTX therapy
Sponsors
NYU Langone Health
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
RA cohort * Receiving MTX at stable doses of 10 to 25 mg weekly for at least 12 weeks * Have a DAS28 of 3.2 or higher (The level of disease activity is considered to be low if the DAS28 is 3.2 or less) (Prevoo et al., 1995) OA cohort * Diagnosis of osteoarthritis made by physician.
Exclusion criteria
RA cohort * History of sensitivity to study medications or any of their excipients * Previous intolerance to MTX * Current treatment with antiplatelet therapy * Absolute indication for anti-platelet therapy * Need for chronic oral anticoagulant therapy * Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy) * Renal failure (eGFR \<30 or requiring dialysis) * A known bleeding diathesis, hemostatic or coagulation disorder, or prior major bleeding * Prior stroke * Active pathological bleeding * History of intracranial haemorrhage * Life expectancy \<12 months based on investigator's judgement * Patients considered to be at risk of bradycardic events (e.g., known sick sinus syndrome or second or third degree atrioventricular \[AV)\] block) unless already treated with a permanent pacemaker * Anemia (hematocrit \< 27%) * Platelet count \< 100,000/ml * Concomitant use of strong CYP 3A inhibitors or inducers * History of thrombocytopenia or neutropenia * Pregnant or nursing women, or females with a positive pregnancy test at screening * Females of child bearing potential not using acceptable method of birth control prior to or during study * Concern for inability of the patient to comply with study procedures and/or follow up (eg, alcohol or drug abuse) OA cohort: * History of sensitivity to study medications or any of their excipients * Current treatment with antiplatelet therapy * Absolute indication for anti-platelet therapy * Need for chronic oral anticoagulant therapy * Severe hepatic impairment (eg, ascites and/or clinical signs of coagulopathy) * Renal failure (eGFR \<30 or requiring dialysis) * A known bleeding diathesis, hemostatic or coagulation disorder, or prior major bleeding * Prior stroke * Active pathological bleeding * History of intracranial haemorrhage * Life expectancy \<12 months based on investigator's judgement * Anemia (hematocrit \< 27%) * Platelet count \< 100,000/ml * History of thrombocytopenia or neutropenia * Pregnant or nursing women, or females with a positive pregnancy test at screening * Females of child bearing potential not using acceptable method of birth control prior to or during study * Concern for inability of the patient to comply with study procedures and/or follow up (eg, alcohol or drug abuse)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Activity Score for 28-joint Counts (DAS28) | 30 Days | The DAS28 is a composite score derived from 4 of these measures. This '28' version is a simplification of the original DAS score, which requires 44 joints to be counted. Other versions of the DAS28 allow the CRP to be used instead of the ESR, or the omission of either. To calculate the DAS28 your rheumatologist or specialist nurse will:- count the number of swollen joints (out of the 28), count the number of tender joints (out of the 28), take blood to measure the erythrocyte sedimentation rate (ESR) or C reactive protein (CRP), ask you (the patient) to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). These results are then fed into a complex mathematical formula to produce the overall disease activity score. A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission. The total scale range is from 2 to 10, with higher scores indicating more disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Visual Analog Scale Disease Activity | 30 Days | The VAS is a psychometric response scale that ranges from no pain (0) to worst pain (100); patients mark a line on a continuum to indicate how they are feeling. Provides global assessment of RA severity. |
| Change in Brachial Artery Diameter | Baseline, 30 Days | Endothelial function is characterized by flow-mediated vasodilation of the brachial artery, which is measured by comparing the brachial artery diameter at rest the diameter after increased forearm blood flow (reactive hyperemia). Brachial artery reactivity testing (BART) is a noninvasive technique for evaluating endothelial function |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rheumatoid Arthritis -Receiving Methotrexate at stable doses of 10 to 25 mg weekly for at least 12 weeks
Ticagrelor
MTX therapy | 7 |
| Osteoarthritis -Diagnosis of osteoarthritis made by physician.
MTX therapy | 2 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | Rheumatoid Arthritis | Osteoarthritis |
|---|---|---|---|
| Age, Continuous | 48 years STANDARD_DEVIATION 16 | 48 years STANDARD_DEVIATION 16 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 5 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 0 Participants |
| Region of Enrollment United States | 9 participants | 7 participants | 2 participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 2 |
| other Total, other adverse events | 0 / 7 | 0 / 2 |
| serious Total, serious adverse events | 0 / 7 | 0 / 2 |
Outcome results
Primary
Disease Activity Score for 28-joint Counts (DAS28)
The DAS28 is a composite score derived from 4 of these measures. This '28' version is a simplification of the original DAS score, which requires 44 joints to be counted. Other versions of the DAS28 allow the CRP to be used instead of the ESR, or the omission of either. To calculate the DAS28 your rheumatologist or specialist nurse will:- count the number of swollen joints (out of the 28), count the number of tender joints (out of the 28), take blood to measure the erythrocyte sedimentation rate (ESR) or C reactive protein (CRP), ask you (the patient) to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). These results are then fed into a complex mathematical formula to produce the overall disease activity score. A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission. The total scale range is from 2 to 10, with higher scores indicating more disease activity.
Time frame: 30 Days
Population: The Osteoarthritis arm was removed; no data was collected for this arm due to low enrollment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis | Disease Activity Score for 28-joint Counts (DAS28) | Baseline | 5.7 score on a scale | Standard Deviation 0.4 |
| Rheumatoid Arthritis | Disease Activity Score for 28-joint Counts (DAS28) | 30 days | 4.3 score on a scale | Standard Deviation 0.8 |
Secondary
Change in Brachial Artery Diameter
Endothelial function is characterized by flow-mediated vasodilation of the brachial artery, which is measured by comparing the brachial artery diameter at rest the diameter after increased forearm blood flow (reactive hyperemia). Brachial artery reactivity testing (BART) is a noninvasive technique for evaluating endothelial function
Time frame: Baseline, 30 Days
Population: The Osteoarthritis arm was removed; no data was collected for this arm due to low enrollment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis | Change in Brachial Artery Diameter | Baseline | 2.5 mm | Standard Deviation 0.9 |
| Rheumatoid Arthritis | Change in Brachial Artery Diameter | 30 days | 2.5 mm | Standard Deviation 1.1 |
Secondary
Visual Analog Scale Disease Activity
The VAS is a psychometric response scale that ranges from no pain (0) to worst pain (100); patients mark a line on a continuum to indicate how they are feeling. Provides global assessment of RA severity.
Time frame: 30 Days
Population: The Osteoarthritis arm was removed; no data was collected for this arm due to low enrollment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rheumatoid Arthritis | Visual Analog Scale Disease Activity | Baseline | 47 Units on VAS scale | Standard Deviation 22 |
| Rheumatoid Arthritis | Visual Analog Scale Disease Activity | 30 days | 23 Units on VAS scale | Standard Deviation 18 |