A Study of MabThera (Rituximab) in Patients With Rheumatoid Arthritis Who Have Failed on One Prior Anti-TNF Therapy (RESET)
2017年7月6日 更新者：Hoffmann-La Roche
Rituximab Phase IIIb Open-label, Multi-centre Assessment of Safety and Effectiveness in Patients With RA Following an Inadequate Response to One Prior Anti-TNF Inhibitor (RESET)
This study will evaluate the safety and effectiveness of MabThera (rituximab) in patients with active rheumatoid arthritis who are receiving methotrexate, and who have a previous or current inadequate response to one prior anti-TNF therapy.
All patients will receive MabThera 1000 mg as an intravenous infusion on days 1 and 15.
After the initial study phase of 24 weeks, eligible patients may receive one re-treatment with MabThera.
The anticipated time on study treatment is 48 weeks.
調査の概要
研究の種類
介入
入学 (実際)
120
段階
- フェーズ 3
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alberta
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Edmonton、Alberta、カナダ、T6G 2B7
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Edmonton、Alberta、カナダ、T5M 0H4
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British Columbia
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Kelowna、British Columbia、カナダ、V1Y 3G8
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Vancouver、British Columbia、カナダ、V5Z 3Y1
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Victoria、British Columbia、カナダ、V8V 3P9
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Manitoba
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Winnipeg、Manitoba、カナダ、R3A 1M4
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Newfoundland and Labrador
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St John's、Newfoundland and Labrador、カナダ、A1A 5E8
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St John's、Newfoundland and Labrador、カナダ、A1C 5B8
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Ontario
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Hamilton、Ontario、カナダ、L8N 1Y2
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Hamilton、Ontario、カナダ、L8S 4J9
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Mississauga、Ontario、カナダ、L5M 2V8
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Nepean、Ontario、カナダ、K2G 6E2
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Ottawa、Ontario、カナダ、K1H 8L6
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Ottawa、Ontario、カナダ、K1S 1C2
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Thunder Bay、Ontario、カナダ、P7B 5G3
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Toronto、Ontario、カナダ、M4K 1N2
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Toronto、Ontario、カナダ、M5T 2S8
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Toronto、Ontario、カナダ、M5G 1X5
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Windsor、Ontario、カナダ、N8X 5A6
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Quebec
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Laval、Quebec、カナダ、H7G 2E6
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Montreal、Quebec、カナダ、H1T 2M4
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Montreal、Quebec、カナダ、H3T 1E2
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Montreal、Quebec、カナダ、H2L 1S6
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Montreal、Quebec、カナダ、H2L 4M1
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Quebec City、Quebec、カナダ、G1V 3M7
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Sainte-foy、Quebec、カナダ、G1W 4R4
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Sherbrooke、Quebec、カナダ、J1H 5N4
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St-eustache、Quebec、カナダ、J7P 4J2
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Trois-rivieres、Quebec、カナダ、G8Z 1Y2
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Boras、スウェーデン、50182
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Falun、スウェーデン、79182
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Goeteborg、スウェーデン、41345
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Jonkoping、スウェーデン、551 85
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Kalmar、スウェーデン、39185
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Karlskrona、スウェーデン、37185
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Lulea、スウェーデン、97180
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Malmoe、スウェーデン、20502
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Oskarstroem、スウェーデン、31392
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Skoevde、スウェーデン、54185
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Stockholm、スウェーデン、18288
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Sundsvall、スウェーデン、85186
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～80年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
Inclusion Criteria:
- Adult patients, 18-80 years of age
- Moderate to severe active rheumatoid arthritis
- Inadequate response to a single previous or current treatment with an anti-TNF agent
- Methotrexate for at least 12 weeks, at a stable dose over the past 4 weeks
Exclusion Criteria:
- Previous treatment with MabThera
- Use of an anti-TNF agent within past 8 weeks (4 in the case of etanercept)
- Concurrent treatment with any Disease Modifying Anti-Rheumatic Drug (DMARD) other than methotrexate
- Active infection, or history of serious or chronic infection
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：シングルアーム
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1000 mg intravenously on Days 1 and 15
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Percentage of Participants With Adverse Events During the Initial Treatment Period - Overall Summary
時間枠：Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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Percentage of participants who reported an AE or serious AE (SAE), a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
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Days 1, 2, 15, and 16 and Week 48 of Initial treatment period
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Percentage of Participants With Adverse Events During the Re-Treatment Period - Overall Summary
時間枠：Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.
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Days 1, 2, 15, and 16 and Week 48 of Re-treatment period
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Percentage of Participants Meeting American College of Rheumatology (ACR) Response Criteria During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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ACR20/50/70, defined as ≥20 percent (%), 50%, or 70% improvement, respectively, compared to baseline in tender joint count (TJC) and swollen joint count (SJC), and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; Health Assessment Questionnaire - Disability Index (HAQ-DI); and an acute phase reactant (erythrocyte sedimentation rate [ESR] or C-Reactive Protein [CRP]).
If CRP was missing or not done, then ESR was used.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting ACR Response Criteria During the Re-treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
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ACR20/50/70, defined as ≥20%, 50%, or 70% improvement, respectively, compared to baseline in TJC and SJC, and 20%/50%/70% improvement in at least 3 of 5 additional ACR core set variables: Patient Assessment of Pain; Patient's Global Assessment of Disease Activity; Physician's Global Assessment of Disease Activity; HAQ-DI; and an acute phase reactant (ESR or CRP).
If CRP was missing or not done, then ESR was used.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants With Complete Clinical Response Per ACR Criteria During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
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Complete clinical response was defined as having an ACR70 for at least 13 weeks.
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Weeks 12 and 24 of Re-treatment period
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Percentage of Participants Meeting European League Against Rheumatism (EULAR) Response Criteria During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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The EULAR response criteria were based on the assessment of disease activity using the DAS28.
The EULAR response criteria included not only change in disease activity but current disease activity.
To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity.
There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score less than or equal to [≤]3.2), moderate (DAS28 score greater than [>]3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Percentage of Participants Meeting EULAR Response Criteria During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
The EULAR response criteria were based on the assessment of disease activity using the DAS28.
The EULAR response criteria included not only change in disease activity but current disease activity.
To be classified as responders, participants had to have a significant change in DAS28 and a low current disease activity.
There were 4 categories of EULAR response rates: good, moderate, good/moderate, and none.
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in DAS28 During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in DAS28 During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score <2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
A change of 1.2 units in DAS28 in an individual participant was considered a significant change.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in SJC During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in SJC During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in TJC During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in TJC During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
Joints assessed for swelling consisted of shoulders, elbows, wrists, interphalangeal (digit 1), distal interphalangeal joints (digits 2-5), proximal interphalangeal joints (digits 2-5), metacarpophalangeal joints (digits 1-5), and knees.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Physician Global Assessment of Disease Activity was measured using a 100-mm visual analog scale (VAS) where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The physician marked the line and the distance from the left edge was measured in mm.
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Weeks 4, 12, 24, 36, and 48 of Initial treatment period
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Change From Baseline in Physician's Global Assessment of Disease Activity During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
Physician Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The physician marked the line and the distance from the left edge was measured in mm.
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Weeks 12 and 24 of Re-treatment period
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Change From Baseline in Patient Global Assessment of Disease Activity Score During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The participant was asked to marked the line and the distance from the left edge was measured in mm.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in Patient Global Assessment of Disease Activity During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
|
Patient Global Assessment of Disease Activity was measured using a 100-mm VAS where the extreme left end of the line was 0 = no disease activity and the extreme right end of the line was 100 = maximum disease activity.
The participant was asked to marked the line and the distance from the left edge was measured in mm.
|
Weeks 12 and 24 of Re-treatment period and Week 4 after last maintenance
|
|
Change From Baseline in Patient Global Assessment of Pain During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain.
The participant was asked to mark the line and the distance from the left edge was measured in mm.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in Patient Global Assessment of Pain During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
Patient Global Assessment of Pain was measured using a 100-mm VAS where the extreme left end of the line was 0 = no pain and the extreme right end of the line was 100 = unbearable pain.
The participant was asked to mark the line and the distance from the left edge was measured in mm.
|
Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline HAQ-DI Score During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities.
Participants report amount of difficulty in performing 2-3 specific subcategory items.
Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do).
The highest component score in each of the 8 categories determined the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3).
The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability).
HAQ-DI not computed if > 2 categories were missing.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline HAQ-DI Score During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
HAQ-DI: 20 questions, 8 categories of functioning: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and common usual activities.
Participants report amount of difficulty in performing 2-3 specific subcategory items.
Difficulty score is from 0 to 3 (0 = without any difficulty; 1 = with some difficulty; 2 = with much difficulty; and 3 = unable to do).
The highest component score in each of the 8 categories determines the score for that category, unless aids, devices, and/or help from another person were required which = a score of 2 (unless already 2 or 3).
The 8 category scores were averaged into overall HAQ-DI score ranging from 0 to 3 (0 to 1 = mild to moderate difficulty; 1 to 2 = moderate to severe disability; and 2 to 3 = severe to very severe disability).
HAQ-DI not computed if >2 categories were missing.
|
Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in ESR During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
ESR was measured in mm/hour and was used to determine the acute phase response.
Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in ESR During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
ESR was measured in mm/hour and was used to determine the acute phase response.
Lower ESR values indicate reduction in disease activity; normal reference range: 0-20 mm/hr.
|
Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in CRP During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
CRP levels were measured in milligrams/liter (mg/L) and were used to determine the acute phase response.
A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline CRP During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
CRP levels were measured in mg/L and were used to determine the acute phase response.
A reduction in CRP levels is considered an improvement; normal reference range ≤10 mg/L.
|
Weeks 12 and 24 of Re-treatment period
|
|
Percentage of Participants With Disease Remission According to DAS28 in the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Percentage of Participants With Disease Remission According to DAS28 in the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
The DAS28 scoring used 4 core components: SJC, TJC, Patient's Global Assessment of Disease Activity, and ESR.
The DAS28 has a continuous scale ranging from 0 to 9.4.
The level of disease activity was interpreted as low (DAS28 score ≤3.2), moderate (DAS28 score >3.2 but ≤5.1), or high (DAS28 score >5.1).
A DAS28 score ≤2.6 corresponded to a state of remission according to American Rheumatism Association criteria.
|
Weeks 12 and 24 of Re-treatment period
|
|
Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Total Score During the Initial Treatment Period
時間枠：Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale.
The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue.
Score changes of 4 points or more were considered clinically meaningful.
The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
|
Weeks 4, 12, 24, 36, and 48 of Initial treatment period
|
|
Change From Baseline in FACIT-F Total Score During the Re-Treatment Period
時間枠：Weeks 12 and 24 of Re-treatment period
|
Participant fatigue was evaluated using the FACIT-F scale, a 13-item questionnaire in which the participants were requested to score each item on a 5-point scale.
The FACIT-F scores ranged from 0 to 52, with higher scores representing less fatigue.
Score changes of 4 points or more were considered clinically meaningful.
The total score was a summation of all 13 items, where 2 of the positive items (I have energy; I am able to do my usual activities) were reversed for scoring.
|
Weeks 12 and 24 of Re-treatment period
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2006年7月18日
一次修了 (実際)
2009年3月12日
研究の完了 (実際)
2009年3月12日
試験登録日
最初に提出
2011年1月7日
QC基準を満たした最初の提出物
2011年1月7日
最初の投稿 (見積もり)
2011年1月10日
学習記録の更新
投稿された最後の更新 (実際)
2017年8月15日
QC基準を満たした最後の更新が送信されました
2017年7月6日
最終確認日
2017年6月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。