Escape II Myocardium
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
Data on a small number of patients with Rheumatoid Arthritis (RA) show that patients with RA may have a smaller heart size and altered heart function. There is limited evidence that general inflammation due to RA and inflammation within the heart may lead to a smaller heart size which may precede heart failure in RA. Preliminary data show that all these may improve with treatment with a specific class of medications called Tumor Necrosis Factor (TNF) inhibitors. The investigators hypothesize that RA affects the size and function of the heart via inflammation and that treatment with TNF inhibitors may improve the heart size and function and possibly prevent the development of heart failure in RA.
In order to investigate these hypotheses the investigators are going to identify 50 patients who have joint inflammation that has not responded to treatment with methotrexate. As it would happen under standard of care (even without participation in the study) these patients will receive additional treatment to control their joint disease. The investigators will randomly assign these patients to receive one of two equivalent treatments that are commonly prescribed in clinical practice and in the context of standard of care: either a TNF inhibitor OR the medications sulfasalazine and hydroxychloroquine will be added to methotrexate after randomization. It is known that these two different treatments are equivalent in controlling joint inflammation but is not known if one or the other has a more favorable effect on the heart size and function. The patients will be evaluated at baseline and return 6 months after randomization and will have imaging of their heart with PET scanning and echocardiogram at both time points. Participants will also provide information about their RA, other diseases and will offer blood for testing. The investigators assume (hypothesize) that patients randomly assigned to TNF inhibitor will have improved heart size and better heart function and less inflammation in the heart compared to patients assigned to take the oral medications sulfasalazine and hydroxychloroquine.
| Condition | Intervention |
|---|---|
|
Rheumatoid Arthritis |
Drug: Triple Therapy Drug: TNF inhibitors |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Prevention |
| Official Title: | ESCAPE II MYOCARDIUM: How Rheumatoid Arthritis (RA) and Tumor Necrosis Factor (TNF) Inhibitors Affect the Myocardial Structure and Function. |
- Improvement of left ventricular mass [ Time Frame: 6 months after treatment with TNF inhibitors versus triple therapy ] [ Designated as safety issue: No ]We will evaluate the differential effect TNF inhibitors vs "triple therapy" on LV mass after 6 months of treatment.
- Improvement of Left Ventricular Ejection Fraction. [ Time Frame: After 6 months of treatment with TNF inhibitor versus triple therapy ] [ Designated as safety issue: No ]
- Improvement in the degree of myocardial inflammation (as indicated by FDG uptake in PET scanning) [ Time Frame: 6 months after treatment with TNF inhibitor versus triple therapy ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 50 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | October 2015 |
| Estimated Primary Completion Date: | October 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: TNF Inhibitors |
Drug: TNF inhibitors
Patients will receive one of the FDA approved TNF inhibitors at the approved dosage regimen. Patients will be evaluated during safety visits scheduled every 8 weeks between the 0 and 6 month study visits. At the time of the first safety visit medication tolerability and safety will be evaluated. At the time of the second safety visit if joint disease activity is still moderate or high an increase in the dose or frequency of the TNF inhibitor or a switch to treatment to an alternative/equivalent TNF inhibitor will take place ( there are 5 TNF inhibitors approved at the moment). Other Names:
|
| Active Comparator: Triple Therapy (SSZ+MTX+Plaquenil) |
Drug: Triple Therapy
Patients on triple therapy will be started on 1 gram of sulfasalazine twice daily along with weight adjusted daily Hydroxychloroquine. MTX treatment will be continued. Patients will be evaluated during safety visits scheduled every 8 weeks between the 0 and 6 month study visits. In the first safety visit if joint disease activity is still moderate or high sulfasalazine will be increased to 3 grams daily. At the time of the second safety visit if disease activity remains moderate or high, SSZ and Hydroxychloroquine will be stopped and patients will be switched to Leflunomide (Arava) 10 mg plus methotrexate. Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
INCLUSION CRITERIA
- Diagnosis of Rheumatoid Arthritis by 2010 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) diagnostic criteria
- Age>18 years old
- Moderate to high RA disease activity defined by a CDAI of >10
- Stable dose of Methotrexate for 6 weeks prior to enrollment;
- Stable doses of Nonsteroidal anti-inflammatory drug (NSAID) and prednisone (if already taking these medications) for 2 weeks prior to study
EXCLUSION CRITERIA
- Prior self reported or physician diagnosed CV event (MI; angina; stroke or Transient Ischemic Attach (TIA); Heart Failure (HF); prior CV procedure (e.g., coronary artery bypass graft, angioplasty, valve replacement, pacemaker);
- Contraindications to having a PET-CT scan or receive adenosine or Fludeoxyglucose (FDG).
- Active treatment for Cancer
- Uncontrolled hypertension
- Diabetes
- Smoking
- Treatment with a TNF inhibitor or other biologic currently or within the last 6 months
- Treatment with any non-biologic disease-modifying antirheumatic drug (DMARD) other than MTX in the past two months;
- Untreated positive (tuberculosis skin test) PPD or active tuberculosis
- History of Lymphoma and Melanoma
- Ejection Fraction (EF) < 40% (if not known in advance then the Study Visit I Echocardiogram results will be used to exclude the patient from randomization and follow up)
- Change in NSAID/Prednisone dosage in last 2 weeks
- Participation in other research studies involving imaging/radiation exposure
For control participation (15 controls):
INCLUSION CRITERIA
- Age>18 years old
- Absence of diagnosis of RA. EXCLUSION CRITERIA
- Prior self reported or physician diagnosed CV event (MI; angina; stroke or Transient Ischemic Attach (TIA); Heart Failure (HF); prior CV procedure (e.g., coronary artery bypass graft, angioplasty, valve replacement, pacemaker);
- Contraindications to having a PET-CT scan or receive adenosine or FDG.
- Uncontrolled hypertension.
- Participation in other research studies involving imaging/radiation exposure
Contacts and Locations| Contact: Afshin Zartoshti, MS | 2123054114 | az2200@columbia.edu |
| Contact: Dimitrios Pappas, MD | 2123056327 | dp2544@columbia.edu |
| United States, New York | |
| Columbia University Medical Center | Recruiting |
| New York, New York, United States, 10032 | |
| Contact: Afshin Zartoshti, MS 212-305-4114 az2200@columbia.edu | |
| Contact: Dimitrios Pappas, MD 2123056327 dp2544@columbia.edu | |
| Principal Investigator: Joan M Bathon, MD | |
| Principal Investigator: | Joan M Bathon, MD | Columbia University |
More Information
Additional Information:
No publications provided
| Responsible Party: | Joan M. Bathon, Professor Medicine, Rheumatology, Columbia University |
| ClinicalTrials.gov Identifier: | NCT01548768 History of Changes |
| Other Study ID Numbers: | AAAI1026, 7R01AR050026-07 |
| Study First Received: | March 6, 2012 |
| Last Updated: | January 14, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Columbia University:
|
Rheumatoid Arthritis Cardiovascular disease Myocardium |
TNF-alpha inhibitors ESCAPE Co-morbidities |
Additional relevant MeSH terms:
|
Arthritis Arthritis, Rheumatoid Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Hydroxychloroquine Methotrexate Leflunomide Sulfasalazine Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antirheumatic Agents Therapeutic Uses Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Antineoplastic Agents Dermatologic Agents Folic Acid Antagonists |
ClinicalTrials.gov processed this record on May 19, 2013