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Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis (TIMERA)

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ticagrelor
MTX therapy
Sponsored by
NYU Langone Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Methotrexate (MTX), Ticagrelor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • New York University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Rheumatoid Arthritis

Osteoarthritis

Arm Description

-Receiving Methotrexate at stable doses of 10 to 25 mg weekly for at least 12 weeks

-Diagnosis of osteoarthritis made by physician.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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

Full Information

First Posted
August 17, 2016
Last Updated
September 27, 2021
Sponsor
NYU Langone Health
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1. Study Identification

Unique Protocol Identification Number
NCT02874092
Brief Title
Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis
Acronym
TIMERA
Official Title
Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
November 15, 2016 (Actual)
Primary Completion Date
April 19, 2019 (Actual)
Study Completion Date
June 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Methotrexate (MTX), Ticagrelor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rheumatoid Arthritis
Arm Type
Active Comparator
Arm Description
-Receiving Methotrexate at stable doses of 10 to 25 mg weekly for at least 12 weeks
Arm Title
Osteoarthritis
Arm Type
Active Comparator
Arm Description
-Diagnosis of osteoarthritis made by physician.
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Intervention Type
Drug
Intervention Name(s)
MTX therapy
Primary Outcome Measure Information:
Title
Disease Activity Score for 28-joint Counts (DAS28)
Description
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
Secondary Outcome Measure Information:
Title
Visual Analog Scale Disease Activity
Description
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
Title
Change in Brachial Artery Diameter
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Berger, MD
Organizational Affiliation
New York University Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York University School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States

12. IPD Sharing Statement

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Ticagrelor in Methotrexate-Resistant Rheumatoid Arthritis

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