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Musculoskeletal Ultrasound in Predicting Early Dose Titration With Tocilizumab (RASTS)

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ClinicalTrials.gov Identifier: NCT01717859
Recruitment Status : Completed
First Posted : October 31, 2012
Results First Posted : November 29, 2018
Last Update Posted : May 15, 2019
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Dr. Veena Ranganath, University of California, Los Angeles

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Rheumatoid Arthritis
Intervention Drug: Tocilizumab
Enrollment 74
Recruitment Details Patients were recruited through printed and internet advertisements, direct recruitment of study participants, referrals, review of medical records to identify potential participants, and through IRB approved screening protocol and IRB approved study. Patients were recruited starting on 9/24/14. The recruitment continued through November of 2016.
Pre-assignment Details

16 did not pass inclusion criteria, these patients were not able to be assigned to a study arm: 8 had PDUS<10 4 lab values outside limits

  1. pregnant
  2. changed their mind

1 was taking prednisone.

Also:

4 other patients were assigned to the study arm but were deleted from the study due to the considerations mentioned in the protocol

Arm/Group Title Tocilizumab
Hide Arm/Group Description

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Period Title: Overall Study
Started 54
3 Month 50
Completed 44
Not Completed 10
Reason Not Completed
Adverse Event             5
Moved out of state             1
Patient concerned about mental health             1
Lost to Follow-up             1
Withdrawal by Subject             2
Arm/Group Title Tocilizumab
Hide Arm/Group Description

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Baseline Participants 54
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants
51.87  (15.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants
Female
49
  90.7%
Male
5
   9.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 54 participants
American Indian or Alaska Native
1
   1.9%
Asian
4
   7.4%
Native Hawaiian or Other Pacific Islander
1
   1.9%
Black or African American
9
  16.7%
White
34
  63.0%
More than one race
0
   0.0%
Unknown or Not Reported
5
   9.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 54 participants
54
 100.0%
Disease duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 54 participants
9.94  (7.50)
Disease Activity Score All Joints (DAS28)/ Erythrocyte Sedimentation Rate (ESR)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants
6.30  (1.03)
[1]
Measure Description: DAS28 is a measure of disease activity in rheumatoid arthritis (RA). DAS stands for 'disease activity score' and the number 28 refers to the 28 joints that are examined in this assessment. The calculation takes into account the number of swollen joints, the number of tender joints (both out of 28 assessed joints), the erythrocyte sedimentation rate (ESR), and a self-reported global assessment of health from the patient. DAS28 ranges from 0 to a maximum of 9.48. A DAS28 more than 5.1 implies active disease, less than 3.2 implies low disease activity, and less than 2.6 implies remission.
Clinical Disease Activity Index (CDAI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants
39.04  (11.90)
[1]
Measure Description: CDAI stands for "Clinical Disease Activity Index" and is a measure used to assess rheumatoid arthritis activity. This scale sums the count of swollen joints, the count of tender joints (both out of 28 assessed joints), and the final scores of both a patient global health assessment and a care provider global health assessment for the patient on a continuous scale from 0-10. CDAI ranges from 0 to 76, and <2.8 implies remission, <10.0 implies low disease activity, <22.0 implies moderate disease activity, and >22.0 implies high disease activity.
Health Assessment Questionnaire- Disability Index (HAQ-DI)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants
1.47  (0.60)
[1]
Measure Description: HAQ-DI stands for Health Assessment Questionnaire- Disability Index. HAQ-DI is derived from the HAQ, Health Assessment Questionnaire, developed in the 1980's. The HAQ-DI measures the quality of life of the patient by asking the patient to report answers to their abilities to perform daily life tasks such as getting in and out of bed. It ranges from 0 to a maximum value of 3. Values in the range of 0 to 1 implies the patient has mild difficulties to moderate disability, 1 to 2 implies that the patient has a moderate to severe disability, and 2 to 3 implies a very severe disability.
Max Joint Power Doppler Ultrasound (PDUS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants
29.59  (16.06)
[1]
Measure Description: 34 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents PDUS. The Power Doppler Synovitis Score (PDUS) ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for PDUS represents more severe disease level.
Max Joint Grey-Scale Ultrasound (GSUS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 54 participants
43.61  (14.68)
[1]
Measure Description: 34 joints will be evaluated using a 0 to 3 point scale for each joint and the sum of these represents GSUS. The grey scale synovial hypertrophy score (GSUS) ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. A higher value of the total score for GSUS represents more severe disease level.
1.Primary Outcome
Title Baseline to Month 3 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
Hide Description

34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Power Doppler scores.

This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level.

Time Frame Baseline, 3 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change of Total Power Doppler Synovitis Score 3 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
6.84  (13.09)
2.Secondary Outcome
Title Baseline to Month 6 Change in Total Power Doppler Synovitis Score of 34 Joints (Range 0 - 102)
Hide Description

34 joints will be evaluated using a 0 to 3 point scale for each joint. Power Doppler synovitis score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Power Doppler scores.

This scale is called the Power Doppler Synovitis Score (PDUS). It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for PDUS represents more severe disease level.

Time Frame Baseline, 6 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change of Total Power Doppler Synovitis Score 6 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
13.16  (15.68)
3.Secondary Outcome
Title Baseline to Month 3 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
Hide Description

34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 3 Month Synovial Hypertrophy Scores.

This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level.

Time Frame Baseline, 3 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change Total B-mode Synovial Hypertrophy Score 3 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
5.26  (12.55)
4.Secondary Outcome
Title Baseline to Month 6 Change in Total B-mode Synovial Hypertrophy Score of 34 Joints
Hide Description

34 joints will be evaluated using a 0 to 3 point scale for each joint. Synovial hypertrophy score is the sum of all the joint scores. Change scores are calculated by subtracting Baseline minus 6 Month Synovial Hypertrophy Scores.

This scale is called the Grey Scale Synovial Hypertrophy Score (GSUS). Please note that B-mode is the same as GSUS. It ranges from 0 to 102. Scores of 0 indicate the least amount of inflammation of the joint while scores of 3 indicate the most amount of inflammation. Therefore, a higher value of the total score for GSUS represents more severe disease level.

Time Frame Baseline, 6 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change Total B-mode Synovial Hypertrophy Score 6 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
11.00  (15.32)
5.Secondary Outcome
Title Baseline to Month 3 Change in DAS28/ESR
Hide Description

28 joints will be evaluated for Tender Joint Count (TJC) and Swollen Joint Count (SJC) as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 3 Month Disease Activity Score (DAS) scores.

The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease.

Time Frame Baseline, 3 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change in DAS28/ESR 3 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.20  (1.08)
6.Secondary Outcome
Title Baseline to Month 6 Change in DAS28/ESR
Hide Description

28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit, finally the ESR lab value will be included in the total calculation. Change scores are calculated by subtracting Baseline minus 6 Month DAS scores.

The scale being used is called the Disease Activity Score for 28 Joints (DAS28) using the Erythrocyte Sedimentation Rate (ESR) in the calculation rather than the C Reactive Protein (CRP). The scale ranges from 0 to 9.4. Values of DAS28 below 2.6 imply remission, below 3.2 imply low disease activity and greater than 5.1 implies active disease.

Time Frame Baseline, 6 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change in DAS28/ESR 6 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.32  (1.22)
7.Secondary Outcome
Title Baseline to Month 3 Change in CDAI
Hide Description

28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 3 Month CDAI scores.

The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity.

Time Frame Baseline, 3 month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change in CDAI 3 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
9.64  (10.72)
8.Secondary Outcome
Title Baseline to Month 6 Change in CDAI
Hide Description

28 joints will be evaluated for TJC and SJC as well as patient and physician global values assessed at the time of each visit. Change scores are calculated by subtracting Baseline minus 6 Month CDAI scores.

The scale being used is called the Clinical Disease Activity Index (CDAI) and has a range of 0 to 76. Values of CDAI below 2.8 imply remission, below 10 imply low disease activity, below 22 imply moderate disease activity, and above 22 implies high disease activity.

Time Frame Baseline, 6 Month
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mean Change in CDAI 6 Month
Hide Arm/Group Description:

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
16.70  (12.27)
Time Frame 3 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tocilizumab
Hide Arm/Group Description

All subjects will receive tocilizumab.

Tocilizumab: All subjects will start at 4mg/kg. After 3 months, if DAS28 > 3.2, dosage will be escalated to 8 mg/kg.

All-Cause Mortality
Tocilizumab
Affected / at Risk (%)
Total   0/54 (0.00%)    
Hide Serious Adverse Events
Tocilizumab
Affected / at Risk (%) # Events
Total   1/54 (1.85%)    
Reproductive system and breast disorders   
Breast Cancer   1/54 (1.85%)  1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Tocilizumab
Affected / at Risk (%) # Events
Total   51/54 (94.44%)    
Blood and lymphatic system disorders   
Anemia   5/54 (9.26%) 
Dyslipidemia   3/54 (5.56%) 
Hypokalemia   8/54 (14.81%) 
Leukopenia   12/54 (22.22%) 
Neutropenia   4/54 (7.41%) 
Thrombocytopenia   4/54 (7.41%) 
Cardiac disorders   
Hypercholesterolemia   17/54 (31.48%) 
Gastrointestinal disorders   
Abdominal Pain   3/54 (5.56%) 
Diarrhea   6/54 (11.11%) 
Loose Stool   3/54 (5.56%) 
General disorders   
Falling Down   3/54 (5.56%) 
Fatigue   4/54 (7.41%) 
Headaches   10/54 (18.52%) 
Increased Pain   3/54 (5.56%) 
Insomnia   4/54 (7.41%) 
Musculoskeletal and connective tissue disorders   
Rheumatoid Arthritis Flare   21/54 (38.89%) 
Renal and urinary disorders   
Urinary Tract Infection   3/54 (5.56%) 
Respiratory, thoracic and mediastinal disorders   
Dry Cough   5/54 (9.26%) 
Upper Respiratory Infection   21/54 (38.89%) 
Vascular disorders   
Bruises on Different Body Sites   6/54 (11.11%) 
Hypertension   3/54 (5.56%) 
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Veena K. Ranganath
Organization: UCLA
Phone: 310-825-4321
EMail: vranganath@mednet.ucla.edu
Layout table for additonal information
Responsible Party: Dr. Veena Ranganath, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT01717859    
Other Study ID Numbers: ML28542
ML28542 ( Other Identifier: Genentech Inc. )
First Submitted: October 19, 2012
First Posted: October 31, 2012
Results First Submitted: July 9, 2018
Results First Posted: November 29, 2018
Last Update Posted: May 15, 2019