Evaluation of EULAR-RAID Score in Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

— Rainbow  

Official title:

Open-Label Study To Evaluate The EULAR-RAID Score, Rheumatoid Arthritis Impact Of Disease Score, In Rheumatoid Arthritis Patients Eligible To Etanercept And Who Will Receive Etanercept

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00768053
• Other study ID #: 0881X1-4508
• Secondary ID: B1801019
• Status: Completed
• Phase: Phase 4
• First received: October 3, 2008
• Last updated: July 28, 2011
• Start date: October 2008
• Est. completion date: April 2010

Study information

• Verified date: July 2011
• Source: Wyeth is now a wholly owned subsidiary of Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

The Disease Activity Score (DAS) is a system of measurement developed in the 1980s that uses certain criteria, including joint counts and patient perceived disease activity, to measure disease activity in people with Rheumatoid Arthritis . More recently, the European League against Rheumatism (EULAR) has developed a new system of measurement known as the Rheumatoid Arthritis Impact of Disease score, or EULAR-RAID score. The EULAR-RAID score is a composite score based on patient reported outcomes, and includes such criteria as pain, functional disability, fatigue, sleep disturbances, coping, overall assessment of physical well being and overall assessment of psychological well being. The objective of this study is to evaluate the practical modalities and performance of the EULAR- RAID score in patients with rheumatoid arthritis who have been prescribed etanercept as part of usual medical practice.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 108
• Est. completion date: April 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient aged up to or equal 18 years

• Meet the 1987 ACR Revised Criteria for Rheumatoid Arthritis.

• Active rheumatoid arthritis with a DAS greater than 3,2 and one of the two followings : Objective evidence of 4 clinical synovitis or CRP (plasma C-reactive protein) greater than 10 mg/l or ESR (erythrocyte sedimentation rate) greater than 28 mm/h

• Failure of MTX, taken for at least 3 months and at least 15 mg/wk or maximal tolerated dosage . In patients with contraindications or intolerance to MTX, failure of another drug with structural efficacy (leflunomide or sulfasalazine), taken for at least 3 months at the optimal tolerated dosage Concomitant treatment for RA : DMARDs, corticosteroids, NSAIDs and analgesics are permitted. DMARDs and corticosteroids should be stable between screening and baseline visits.

• Functional status Class I, II or III as defined by American College of Rheumatology (ACR) Revised Criteria.

• Negative serum beta-human chorionic gonadotropin (beta-HCG) pregnancy test at screening for all women of childbearing potential. Sexually active women of childbearing potential must use a medically acceptable form of contraception. Medically acceptable forms of contraception include oral contraceptives, injectable or implantable methods, intrauterine devices, or properly used barrier contraception. Sexually active men must agree to use a medically accepted form of contraception during the study.

• Able and willing to self-inject ETN or have a designee who can do so.

• Able to store injectable test article at 2 Celcius degree to 8 Celcius degree

Exclusion Criteria:

• Prior experience of biologic treatment for their RA including ETN.

• Sepsis or risk of sepsis.

• Current or recent infections, including chronic or localized.

• Planned orthopedic surgery within 3 months (for RA disease)

• History of orthopedic surgery 1 month before screening

• Latex sensitivity.

• Vaccination with live vaccine in the last 4 weeks, or expected to require such vaccination during the course of the study.

• Previous clinical trial involvement in the last 3 months.

• Patients with the following conditions or risk factors should only be entered into the study if the investigator has conducted and documented a full risk/benefit evaluation

• History of recurring or chronic infection, or underlying condition which may predispose patients to infections e.g. tuberculosis (TB) infection (Note: follow SmPC and French guidelines for appropriate screening and treatment of TB in the setting of anti-tumor necrosis factor (anti-TNF) therapy. Patients with latent TB (contact with TB patients, history of primary TB, intradermal test with 5 IU of tuberculin greater than 5 mm, or radiographic lung density greater than 1 cm and consistent with TB) should receive appropriate prophylactic therapy as recommended by the French Agency for healthcare Product Safety (AFSSAPS, http//afassaps.sante.fr/), serious infection (infection associated with hospitalization and/or intravenous antibiotics) within 1 month of test article administration or active infection at screening, open cutaneous ulcers, known human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) positive.

• Current or prior history of blood dyscrasias. Abnormal safety baseline blood test e.g. hemoglobin <= 85 g/L; hematocrit less than 27 %; platelet count less than 125 x 109/L; white blood cell count less than 3.5 x 109/L; serum creatinine greater than 175 µmol/L; aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) greater than 2 times the laboratory's upper limit of normal.

• Pre-existing or recent onset central nervous system (CNS) demyelinating disease.

• Cardiovascular conditions, e.g., myocardial infarction within 12 months of the screening visit, unstable angina pectoris, class III or IV congestive heart failure as defined by the New York Heart Association classification or decompensated congestive heart failure.

• Uncontrolled conditions, e.g., diabetes mellitus, hypertension (defined as screening systolic blood pressure greater than 160 mm Hg or screening diastolic blood pressure greater than 100 mm Hg), severe pulmonary disease requiring hospitalization or supplemental oxygen.

• At increased risk of malignancy.

• Reasonable expectation that the subject will not be able to satisfactorily complete the study.

• History of or current psychiatric illness, alcohol or drug abuse that would interfere with the subject's ability to comply with protocol requirements or give informed consent.

• Employment by the investigator or reporting directly or indirectly to the investigator.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Etanercept
Etanercept 50 mg once a week

Locations

Country	Name	City	State
France	Pfizer Investigational Site	Amiens
France	Pfizer Investigational Site	Amiens
France	Pfizer Investigational Site	Belfort
France	Pfizer Investigational Site	Berck sur Mer
France	Pfizer Investigational Site	Bonneville Cedex
France	Pfizer Investigational Site	Cahors
France	Pfizer Investigational Site	Corbeil-Essonnes
France	Pfizer Investigational Site	Créteil
France	Pfizer Investigational Site	Dijon
France	Pfizer Investigational Site	Lomme
France	Pfizer Investigational Site	Montpellier
France	Pfizer Investigational Site	Mulhouse
France	Pfizer Investigational Site	Paris
France	Pfizer Investigational Site	PARIS Cedex 14
France	Pfizer Investigational Site	Rodez Cedex 9
France	Pfizer Investigational Site	Saint-priest En Jarez
France	Pfizer Investigational Site	Valenciennes
Monaco	Pfizer Investigational Site	Monaco

Sponsors (5)

Lead Sponsor	Collaborator
Wyeth is now a wholly owned subsidiary of Pfizer	depolabo, Lincoln Medical and Mental Health Center, SODIA, Umanis

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reliability of the European League Against Rheumatism - Rheumatism Arthritis Impact of Disease (EULAR-RAID) Score	EULAR-RAID score reliability assessed using an intraclass correlation coefficient (using a consistency definition where the between-measure variance is excluded from the denominator variance and its 95% confidence interval) and the standard error of measurement (SEM) and its 95% confidence interval (CI). A higher intraclass correlation coefficient (ICC) indicates greater score reliability (0.0 to 0.10=virtually none; 0.11 to 0.40=slight; 0.41 to 0.60=fair; 0.61 to 0.80=moderate; 0.81 to 1.00=substantial).	Screening, baseline	No
Primary	Simplicity: Time for Completion of the EULAR-RAID Questionnaire	EULAR-RAID is an assessment of patient reported outcomes for pain, functional disability, fatigue, sleep disturbance, coping, overall assessments of physical well-being and emotional well-being based on 7 numerical rating scales (NRS) questions. NRS individual questions with range of 0 (not affected, very good) to 10 (most affected) weighted and calculated with a total score range of 0 (not affected, very good) to 10 (most affected).	Baseline up to Week 12	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Disease Activity Score Based on 28-joints Count (DAS28)	DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity question measured on an 11-point rating scale scored 0 [none] to 10 [extreme]). Face validity assessed using a correlation coefficient between the EULAR-RAID score and the DAS28. A higher correlation coefficient indicates greater EULAR-RAID score validity.	Baseline, Week 4	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Disease Activity Score Based on 28-joints Count (DAS28): Week 12	DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity question measured on an 11-point rating scale scored 0 [none] to 10 [extreme]). Face validity assessed using a correlation coefficient between the EULAR-RAID score and the DAS28. A higher correlation coefficient indicates greater EULAR-RAID score validity.	Week 12	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Disease Activity Score Based on 28-joints Count (DAS28): Time-normalized Average	Time-normalized average is the area under the curve (AUC) / time between first and last observations. DAS28 calculated from number of swollen joints and painful joints using 28 joints count, ESR (mm/hour) and patient's global assessment of disease activity (participant rated arthritis activity question measured on an 11-point rating scale scored 0 [none] to 10 [extreme]). Face validity assessed using a correlation coefficient between the EULAR-RAID and DAS28 scores. A higher correlation coefficient indicates greater EULAR-RAID score validity.	Baseline, Last observation up to Week 12	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Patient Global Assessment (PGA) of Health Status	PGA of health status is a single-item participant rated response to the question "in general, how would you rate your health over the last 2 to 3 weeks"; scored 0 (very well) to 10 (extremely bad). Face validity assessed using a correlation coefficient between the EULAR-RAID score and the PGA. A higher correlation coefficient indicates greater EULAR-RAID score validity (best >0.85).	Baseline, Week 4	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Patient Global Assessment (PGA) of Health Status: Week 12	PGA of health status is a single-item participant rated response to the question "in general, how would you rate your health over the last 2 to 3 weeks"; scored 0 (very well) to 10 (extremely bad). Face validity assessed using a correlation coefficient between the EULAR-RAID score and PGA health status score. A higher correlation coefficient indicates greater EULAR-RAID score validity (best >0.85).	Week 12	No
Primary	Face Validity: Correlation Coefficients of the EULAR-RAID Score With the Patient Global Assessment (PGA) of Health Status: Time-normalized Average	Time-normalized average is the area under the curve (AUC) / time between first and last observations. PGA of health status is a single-item participant rated response to the question "in general, how would you rate your health over the last 2 to 3 weeks"; scored 0 (very well) to 10 (extremely bad). Face validity assessed using a correlation coefficient between the EULAR-RAID score and PGA health status score. A higher correlation coefficient indicates greater EULAR-RAID score validity (best >0.85).	Baseline, Last observation up to Week 12	No
Primary	Sensitivity to Change of the EULAR-RAID Score: Change From Baseline to Week 4	Sensitivity to change analyzed by testing if the difference of change from baseline of EULAR-RAID score minus the change from baseline of each component (pain, functional disability, fatigue, sleep disturbance, coping, overall physical and emotional well-being with score range 0 [not affected, very good] to 10 [most affected]) was different from 0 or not. Results expressed as standardized response mean (SRM) calculated as ratio of mean change over standard deviation of the change. A non significant test (p value =0.05) means the component had a significant influence to global EULAR RAID score.	Baseline, Week 4	No
Primary	Sensitivity to Change of the EULAR-RAID Score: Change From Baseline to Week 12	Sensitivity to change analyzed by testing if the difference of change from baseline of EULAR-RAID score minus the change from baseline of each component (pain, functional disability, fatigue, sleep disturbance, coping, overall physical and emotional well-being with score range 0 [not affected, very good] to 10 [most affected]) was different from 0 or not. Results expressed as standardized response mean (SRM) calculated as ratio of mean change over standard deviation of the change. A non significant test (p value =0.05) means the component had a significant influence to global EULAR RAID score.	Baseline, Week 12	No
Secondary	Percentage of Participants Achieving a Moderate or Good EULAR Response Rate at Week 12	EULAR response rate is based on DAS28. For DAS28 =3.2 at observation (low disease activity), change from baseline of <-1.2=good response or =-1.2 to <-0.6=moderate response; DAS28 >3.2 to 5.1 at observation (moderate or high disease activity), change from baseline of <-1.2 or =-1.2 to <-0.6=moderate response; DAS28 >5.1 (high disease activity) at observation, change from baseline of <-1.2=moderate response. DAS28 calculated using the 28 joints count, ESR mm/hour, and PGA of disease activity (participant rated arthritis activity measured on 11-point rating scale: 0 [none] to 10 [extreme]).	Week 12	No
Secondary	Minimal Clinically Important Improvement (MCII) of the EULAR-RAID Score: 75th Percentile of Change at Week 4 and Week 12	MCII is a 2-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours. Question 1: in comparison to study start (Improved, No Change, or Worse). Question 2: if response was Improved, participant rated how important the improvement was (Very important, Moderately important, Slightly important, or Not important at all). The MCII score is defined as the 75th percentile of the change in EULAR-RAID score between baseline and observation among participants whose evaluation of the response therapy at observation was Moderately or Slightly important improvement.	Week 4, Week 12	No
Secondary	Percentage of Participants Achieving a Minimal Clinically Important Improvement (MCII) Score at Week 4 Who Had Moderately or Slightly Important Improvement at Week 4, Week 12, or Last Observation (Last Obs)	MCII is a 2-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours. Question 1: in comparison to study start (Improved, No change, or Worse). Question 2: if response was Improved, participant rated how important the improvement was (Very important, Moderately important, Slightly important, or Not important at all). MCII score at Week 4 calculated on participants with Moderately or Slightly important improvement (Mod/Slightly Imp Improvement) achieved at observation.	Week 4, Week 12, and Last observation up to Week 12	No
Secondary	Percentage of Participants Achieving a Minimal Clinically Important Improvement Score at Week 12 Who Had Moderately or Slightly Important Improvement at Week 4, Week 12, or Last Observation (Last Obs)	MCII is a 2-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours. Question 1: in comparison to study start (Improved, No change, or Worse). Question 2: if response was Improved, participant rated how important the improvement was (Very important, Moderately important, Slightly important, or Not important at all). MCII score at Week 12 calculated on participants with Moderately or Slightly important improvement (Mod/Slightly Imp Improvement) achieved at observation.	Week 4, Week 12, and Last observation up to Week 12	No
Secondary	Patient Acceptable Symptom State (PASS) of the EULAR-RAID Score: 75th Percentile of Change at Week 4 and Week 12	PASS is a 1-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours (If you were to remain in the next few months as you were during the last hours, would this be Acceptable or Unacceptable to you?). PASS score is defined as the 75th percentile of the change in EULAR-RAID score between baseline and observation among participants whose evaluation of their symptom state at observation was Acceptable.	Week 4, Week 12	No
Secondary	Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) Score at Week 4 Who Had an Acceptable Symptom State at Week 4, Week 12, or Last Observation (Last Obs)	PASS is a 1-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours (If you were to remain in the next few months as you were during the last hours, would this be acceptable or unacceptable to you?). PASS score at Week 4 calculated on participants with Acceptable symptom state achieved at observation.	Week 4, Week 12, and Last observation up to Week 12	No
Secondary	Percentage of Participants Achieving a Patient Acceptable Symptom State (PASS) Score at Week 12 Who Had an Acceptable Symptom State at Week 4, Week 12, or Last Observation (Last Obs)	PASS is a 1-question assessment of how rheumatoid arthritis has affected the participant in the last 48 hours (If you were to remain in the next few months as you were during the last hours, would this be acceptable or unacceptable to you?). PASS score at Week 12 calculated on participants with Acceptable symptom state achieved at observation.	Week 4, Week 12, and Last observation up to Week 12	No
Secondary	Percentage of Participants Achieving > 1.2 Improvement in DAS28 at Week 12	DAS28 calculated from number of painful and swollen joints using 28 joints count (PJC, SJC), ESR (mm/hour), and patient's global assessment of disease activity (arthritis activity measured on 11-point rating scale scored 0 [none] to 10 [extreme]). DAS28 score calculated as 0.56*square root (v) (PJC28) + 0.28 *v (SJC28) + 0.70*ln ESR + 0.014*PGA*10. DAS28 score >5.1=higher disease activity; =3.2=low disease activity; <2.6=clinical remission. Achievement of >1.2 improvement defined as decrease in DAS28 >1.2 (i.e., change in DAS28 < -1.2).	Week 12	No
Secondary	Percentage of Participants Achieving Remission (DAS28 <2.6) at Week 12	DAS28 calculated from number of painful and swollen joints using 28 joints count (PJC, SJC), ESR (mm/hour), and patient's global assessment of disease activity (arthritis activity measured on 11-point rating scalescored 0 [none] to 10 [extreme]). DAS28 score calculated as 0.56*square root (v) (PJC28) + 0.28 *v (SJC28) + 0.70*ln ESR + 0.014*PGA*10. DAS28 score >5.1=higher disease activity; =3.2=low disease activity; <2.6=clinical remission.	Week 12	No
Secondary	Percentage of Participants Achieving Low Disease Activity (DAS28 =3.2) at Week 12	DAS28 calculated from number of painful and swollen joints using 28 joints count (PJC, SJC), ESR (mm/hour), and patient's global assessment of disease activity (arthritis activity measured on 11-point rating scale scored 0 [none] to 10 [extreme]). DAS28 score calculated as 0.56*square root (v) (PJC28) + 0.28 *v (SJC28) + 0.70*ln ESR + 0.014*PGA*10. DAS28 score >5.1=higher disease activity; =3.2=low disease activity; <2.6=clinical remission.	Week 12	No
Secondary	Percentage of Participants Achieving > 0.6 DAS28 Response at Week 12	DAS28 calculated from number of painful and swollen joints using 28 joints count (PJC, SJC), ESR (mm/hour), and patient's global assessment of disease activity (arthritis activity measured on 11-point rating scale scored 0 [none] to 10 [extreme]). DAS28 score calculated as 0.56*square root (v) (PJC28) + 0.28 *v (SJC28) + 0.70*ln ESR + 0.014*PGA*10. DAS28 score >5.1=higher disease activity; =3.2=low disease activity; <2.6=clinical remission. Achievement of >0.6 DAS28 response defined as decrease in DAS28 > 0.6 (i.e. change in DAS28 < -0.6).	Week 12	No
Secondary	Time to Achievement of Sustained Low Disease Activity Score (LDAS): DAS28 =3.2	Time to sustained LDAS measured as maintenance of low disease activity score beyond Week 12. DAS28 calculated from number of painful and swollen joints using 28 joints count (PJC, SJC), ESR (mm/hour), and patient's global assessment of disease activity (arthritis activity measured on 11-point rating scale scored 0 [none] to 10 [extreme]). DAS28 score calculated as 0.56*square root (v) (PJC28) + 0.28 *v (SJC28) + 0.70*ln ESR + 0.014*PGA*10. DAS28 score >5.1=higher disease activity; =3.2=low disease activity; <2.6=clinical remission.	Baseline up to Week 12	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 12	American College of Rheumatology 20% (ACR20) response: responder = =20% improvement in tender and swollen joint count and =20% improvement in at least 3 of 5 ACR core measures: patient assessment of pain (scored 1=extreme pain to 6=no pain; score transformed to 0 to 100: higher score indicates less pain), Patient's Global Assessment and Physician's Global Assessment of disease activity (assess arthritis activity; both scored 0=none to 10=extreme), Modified Health Assessment Questionnaire (assess amount of difficulty to perform an activity scored 0=no difficulty to 3=unable to do), and ESR.	Week 12	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 50 Response at Week 12	American College of Rheumatology 50% (ACR50) response: responder = =50% improvement in tender and swollen joint count and =50% improvement in at least 3 of 5 ACR core measures: patient assessment of pain (scored 1=extreme pain to 6=no pain; score transformed to 0 to 100: higher score indicates less pain), Patient's Global Assessment and Physician's Global Assessment of disease activity (assess arthritis activity; both scored 0=none to 10=extreme), Modified Health Assessment Questionnaire (assess amount of difficulty to perform an activity scored 0=no difficulty to 3=unable to do), and ESR.	Week 12	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 70 Response at Week 12	American College of Rheumatology 70% (ACR70) response: responder = =70% improvement in tender and swollen joint count and =70% improvement in at least 3 of 5 ACR core measures: patient assessment of pain (scored 1=extreme pain to 6=no pain; score transformed to 0 to 100: higher score indicates less pain), Patient's Global Assessment and Physician's Global Assessment of disease activity (assess arthritis activity; both scored 0=none to 10=extreme), Modified Health Assessment Questionnaire (assess amount of difficulty to perform an activity scored 0=no difficulty to 3=unable to do), and ESR.	Week 12	No
Secondary	Percentage of Participants With American College of Rheumatology (ACR) 90 Response at Week 12	American College of Rheumatology 90% (ACR90) response: responder = =90% improvement in tender and swollen joint count and =90% improvement in at least 3 of 5 ACR core measures: patient assessment of pain (scored 1=extreme pain to 6=no pain; score transformed to 0 to 100: higher score indicates less pain), Patient's Global Assessment and Physician's Global Assessment of disease activity (assess arthritis activity; both scored 0=none to 10=extreme), Modified Health Assessment Questionnaire (assess amount of difficulty to perform an activity scored 0=no difficulty to 3=unable to do), and ESR.	Week 12	No

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