The CORRONA Treat to Target Trial: Outcomes and Feasibility in a US Population
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Treating to Target (T2T) for Patients With Rheumatoid Arthritis in a US Population: Outcomes and Feasibility|
- Disease Activity, probability of treatment acceleration conditional on disease activity. [ Time Frame: 1 year ]CDAI Score, rates of acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity.
- Disease activity scores, reasons for ineligibility for treatment acceleration, frequency of toxicity, frequency of TAEs. [ Time Frame: 1 year ]CDAI scores, DAS 28, RAPID 3, reasons/frequency of ineligibility for treatment acceleration, frequency of suspected (RA) drug-related toxicity, frequency of TAEs
|Study Start Date:||July 2011|
|Study Completion Date:||July 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
Experimental: Treat to Target Intervention Strategy
Subjects at sites randomized to this arm will be expected to return to the clinic for Monthly Assessments until low disease activity (LDA) defined as CDAI of 10 or less has been achieved. Providers are prompted to accelerate therapy (Treatment Acceleration) at each visit that CDAI is >10 (unless not felt to be medically appropriate or refused by the subject.) Accelerations are expected at least every 3 months, until/unless LDA has been achieved.
Other: Treatment Acceleration
Other: Monthly Assessment
Subjects in the intervention group will be seen as frequently as monthly for subjects not achieving low disease activity (LDA) as defined as CDAI ≤10. Treatment acceleration will be expected to occur as frequently as monthly and at least every 3 months in these subjects, unless contraindicated.
Treatment acceleration for the purposes of this trial include the following options: Change in prescribed treatment or dosage of "traditional" or "biologic" Disease Modifying Anti Rheumatic Drugs (DMARDs) or a change in the route of Methotrexate administration (from oral to subcutaneous)
Monthly disease assessments are expected to be scheduled until the subject has achieved a CDAI of 10 or less (low disease activity).
Other Name: Monthly follow-up visits to rheumatologist
No Intervention: Control Group Treated with Usual Care
Subjects in this arm will be expected to complete study visits with their rheumatologist/study doctor at Baseline, Month 3, Month 6, Month 9 and Month 12. Data collection will occur at each of those visits. Subjects and Providers will continue managing disease per usual practices and do not receive protocol prompts relative to visit frequency or acceleration of therapy, regardless of disease activity level (by CDAI)
Hide Detailed Description
New and existing CORRONA sites and patient participants are recruited to participate as subjects in this 12 month trial examining outcomes and feasibility of implementing a Treat to Target approach to RA disease management, requiring routine monthly monitoring and regular escalations of treatment for subjects not achieving low disease activity (LDA) when compared with a control group of subjects treated with usual care.
Purpose The primary purpose of the study is to determine whether practices implementing a multi-dimensional T2T process can more effectively control active Rheumatoid Arthritis (RA) in patients eligible-for-acceleration compared to those practices which continue usual care. The trial will also determine if the process of treating to target for the selected subjects is different between the two groups.
A wide variety of therapies are used in clinical practice to treat patients with RA. The CORRONA Data Collection Program is designed to collect and document utilization patterns, effectiveness, and safety of DMARDs (Disease Modifying Anti-Rheumatic Drugs), biologic agents, and many other treatments currently used in the management of rheumatic diseases. It is anticipated that the study data may help improve the quality of information upon which clinical decisions are based.
Objectives Co-primary Objectives 1. To measure rates of low disease activity (by CDAI score) between treatment arms (T2T vs usual care) at 12 months.
1a. To assess implementation of a T2T Protocol by comparing rates of acceleration, frequency of visits, time to next visit, and probability of acceleration conditional on disease activity between subjects treated in a T2T intervention group, compared with a control group treated with usual care (UC) at 12 months.
- To determine mediators of differences in LDA rates between the two randomized groups.
- To determine the association between the process of treating to target and LDA (regardless of randomization).
- To determine the proportion of subjects with active RA and moderate to high disease activity by CDAI eligible for acceleration at Baseline that will have achieved low disease activity (LDA) by CDAI at 6 months in subjects treated in a T2T intervention group compared with a control group treated with usual care (UC), and to baseline disease activity.
To compare performance of derived outcome metrics between the T2T intervention and usual care at 6 and 12 months, including:
- DAS28 ESR
- Patient Reported Outcomes- RAPID 3
- To determine the frequency of ineligibility for treatment acceleration due to risks, comorbidities, concomitant medication or clinician judgment in potential T2T study enrollees.
- To compare rates of drug toxicities between the T2T and UC groups over 12 months.
- To compare rates of Targeted Adverse Events (TAEs) between the T2T intervention and UC arms.
Exploratory Objectives To determine the rates and reasons for non-acceleration of subjects with qualifying CDAIs, enrolled in the T2T and UC arms.
Subjects with moderate to severe Rheumatoid Arthritis disease activity (defined as CDAI score >10) will be enrolled in the trial at participating sites. Sites will be randomized to either the Treat to Target or Usual Care arms. Visits will include a Baseline, Month 3, 6,9, and 12 visit for all subjects. In addition, subjects enrolled at sites participating in the Treat to Target Arm that have not achieved low disease activity (CDAI ≤10) will be expected to return for Monthly Assessment visits. Treatment acceleration will be expected to occur as frequently as monthly and at least every 3 months in these subjects, unless contraindicated.
Treatment acceleration for the purposes of this trial include the following options: Initiation or Change in prescribed treatment or dosage of "traditional" or "biologic" Disease Modifying Anti Rheumatic Drugs (DMARDs) or a change in the route of Methotrexate administration (from oral to subcutaneous)
Upon enrollment, physicians and subjects complete Enrollment Questionnaires, including a 28 joint assessment.
Targeted Adverse Event Reporting Qualifying adverse events which occur during participation in the study and are reported on the Targeted Adverse Event (TAE) Questionnaires. TAE Questionnaires are completed and submitted when a flagged event on a Physician Follow-up Questionnaire has been selected. Submission of de-identified source documents (i.e. hospital records, laboratory results, etc.) in support of the reported TAE is required in order to be valid, unless otherwise determined by the CORRONA Organization. The TAE should be simultaneously reported on both the TAE Questionnaire and on the CORRONA Data Collection Program Physician Follow-up Questionnaire visit date that most closely follows the event (unless the TAE occurs on the date of the Follow-up Visit).
In addition, sites will be encouraged to forward CORRONA, Inc.de-identified reports on qualifying Serious Adverse Events within 24 hrs of learning of them using the CORRONA SAE report form.
Data submitted for inclusion in the Database does not include the names, addresses, telephone numbers, email addresses, or social security numbers of subjects. Data from Questionnaires are tracked in the CORRONA Database by a unique CORRONA identifier assigned at the physician's office. A link is maintained at the physician's office between patient-identifying information (e.g., name, address, telephone number) and the unique CORRONA identifier. The physician's office does not share information with CORRONA that is needed to match subject names with these unique CORRONA identifiers.
Site Enrollment: Selected rheumatologists are invited to participate as investigators in the Treat to Target study.Not all rheumatologists who are involved in the CORRONA Data Collection Program will be involved in this study. Physicians are selected carefully to identify sites that have appropriate qualifications and infrastructure to support the trial and comply with applicable regulations and Good Clinical Practices to protect the rights of human subjects. All potential sites are screened for clinical research experience and GCP (Good Clinical Practice) training. Investigators must obtain Institutional Review Board (IRB) approval. Private physician offices and those not affiliated with an academic institution may submit to New England IRB (NEIRB). Sites at academic centers submit to their local institutional IRBs using approved templates and guidelines for submission, or to the NEIRB if this is approved by their institutional IRB.
Subject Informed Consent Informed consent will be obtained by the investigator and/or designee(s). Informed consent is obtained in the office setting, and in accordance with FDA regulations and guidelines prior to commencement of any study-specific related activities. Patient participation is voluntary, and participants may withdraw their consent at any time.
The CORRONA Organization conducts systematic reviews of submitted records. Additionally, all sites participating in the Treat to Target trial are expected to have at least one on-site monitoring visit during the course of the trial. This frequency may be adjusted, as needed, to address data quality issues.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01407419
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01407419
|United States, New York|
|The Center for Rheumatology|
|Albany, New York, United States, 12206|
|Principal Investigator:||Joel Kremer, MD||CORRONA, Inc.|