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Trial record 53 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis (RATE-RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01382940
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : February 19, 2014
Last Update Posted : August 1, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: rituximab
Drug: methotrexate
Drug: methylprednisolone
Drug: acetaminophen
Drug: antihistamine
Enrollment 351
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rituximab
Hide Arm/Group Description Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Period Title: Overall Study
Started 351
Received Day 1 Infusion 351
Received Day 15 Infusions 341
Received Day 168 Infusion 290
Received Day 182 Infusion 278
Completed 278
Not Completed 73
Reason Not Completed
Adverse Event             19
Lost to Follow-up             4
Physician Decision             7
Withdrawal by Subject             23
Protocol Violation             20
Arm/Group Title Rituximab
Hide Arm/Group Description Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Baseline Participants 351
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 351 participants
55.5  (11.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 351 participants
Female
279
  79.5%
Male
72
  20.5%
1.Primary Outcome
Title Percentage of Participants Experiencing Any Infusion-related Reaction (IRR) Associated With the Second Rituximab Infusion
Hide Description The primary criterion for assessing safety of the faster infusion was the incidence of infusion related reaction (IRRs). IRRs were adverse events (AEs) that occurred within 24 hours of beginning infusion that were among a pre-specified list of preferred terms from the Medical Dictionary for Regulatory Activities (MedDRA). "Incidence" is defined as the percentage of participants experiencing an IRR.
Time Frame Within 24 hours of beginning infusion on Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 337
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.5
(4.1 to 9.7)
2.Secondary Outcome
Title Percentage of Participants Experiencing Any Serious IRR (SIRR) Associated With the Second Rituximab Infusion
Hide Description A serious infusion-related reaction (SIRR) is an IRR that meets the definition of a serious adverse event. A serious adverse event (SAE) is any experience that suggests a significant hazard, contraindication, side effect or precaution.
Time Frame Within 24 hours of beginning infusion on Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 337
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 1.1)
3.Secondary Outcome
Title Percentage of Participants Experiencing Any IRR or SIRR Associated With the Third Rituximab Infusion
Hide Description IRRs are AEs that occurred within 24 hours of beginning infusion that were included on a pre-specified list of MedDRA preferred terms, and an SIRR is an IRR that suggests a significant hazard, contraindication, side effect or precaution.
Time Frame Within 24 hours of beginning infusion on Day 168
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 289
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Any IRR
5.9
(3.5 to 9.3)
Any SIRR
0.0
(0.0 to 1.3)
4.Secondary Outcome
Title Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Second Rituximab Infusion
Hide Description The intensity of AEs were graded on a 5-point scale (Grade 1 to 5) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v. 4.0), where Grade 1 indicates "Mild" severity and Grade 5 indicates "Death". The CTCAE defines Grades 3 and 4 as follows: - Grade 3 means "Severe", indicating considerable interference with the patient's daily activities; medical intervention/therapy required; and hospitalization possible. - Grade 4 means "Life-threatening, Disabling", based on extreme limitation in activity; significant medical intervention/therapy required, and hospitalization probable.
Time Frame Within 24 hours of beginning infusion on Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 337
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.6
(0.1 to 2.1)
5.Secondary Outcome
Title Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Second Rituximab Infusion
Hide Description Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment. The CTCAE includes the following severity descriptions: - “Moderate” means mild to moderate interference with the patient’s daily activities, no or minimal medical intervention/therapy required; - "Severe" means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible. If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.
Time Frame During the infusion (a 2-hour period) on Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 15. Four participants who received the Day 15 rituximab infusion were excluded from the primary analysis population because their infusion rates could not be determined.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 337
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
3.9
(2.1 to 6.5)
6.Secondary Outcome
Title Percentage of Participants Experiencing Any Common Toxicity Criteria (CTC) Grade 3 or 4 Adverse Events (AEs) Associated With the Third Rituximab Infusion
Hide Description The intensity of AEs experienced within 24 hours of beginning infusion were graded on NCI's CTCAE (v. 4.0) intensity scale from Grade 1 ("Mild") to Grade 5 ("Death"). Grade 3 AEs are "Severe" and Grade 4 AEs are "Life-threatening, Disabling".
Time Frame Within 24 hours of beginning infusion on Day 168
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 289
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 1.3)
7.Secondary Outcome
Title Percentage of Participants Experiencing the Stopping, Slowing or Interrupting of the Third Rituximab Infusion
Hide Description Participants who experienced a moderate or serious IRR had their infusion interrupted immediately and received aggressive symptomatic treatment. The CTCAE includes the following severity descriptions: - “Moderate” means mild to moderate interference with the patient’s daily activities, no or minimal medical intervention/therapy required; - "Severe" means considerable interference with the patient's daily activities, medical intervention/therapy required, hospitalization possible. If the IRR was moderate, the infusion was not to be restarted before all the symptoms disappeared, and then at half the rate. If the participant tolerated the reduced rate for 30 minutes, the infusion rate was increased to the next rate on the protocol-specified infusion schedule. If the symptoms did not resolve with treatment, the participant was withdrawn from the treatment period of the study. Participants who experienced a severe IRR to rituximab treatment were discontinued from the study.
Time Frame During the infusion (a 2-hour period) on Day 168
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received infusion at the faster rate on Day 168. One participant received the Day 168 rituximab infusion at the labeled rate rather than at the faster rate and was excluded from the analysis population.
Arm/Group Title Rituximab
Hide Arm/Group Description:
Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
Overall Number of Participants Analyzed 289
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.6
(4.0 to 10.1)
Time Frame Adverse events were collected at each visit and during a follow-up telephone visit four weeks after the last rituximab infusion (Day 210).
Adverse Event Reporting Description The safety evaluable population included all participants who received rituximab during the study and had at least one safety assessment during or after the rituximab infusion.
 
Arm/Group Title Rituximab
Hide Arm/Group Description Rituximab intravenous (IV) infusions were administered over a 4.25-hour period on Day 1, and over a 2-hour period on Day 15 (first course) and on Days 168 and 182 (second course). All participants continued to receive methotrexate as prescribed by their treating physician. Premedication included methylprednisolone, an antihistamine and acetaminophen.
All-Cause Mortality
Rituximab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Rituximab
Affected / at Risk (%)
Total   30/351 (8.55%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/351 (0.28%) 
Cardiac disorders   
Atrial fibrillation  1  2/351 (0.57%) 
Cardiac failure congestive  1  1/351 (0.28%) 
Myocardial infarction  1  1/351 (0.28%) 
Pericardial effusion  1  1/351 (0.28%) 
Ear and labyrinth disorders   
Deafness neurosensory  1  1/351 (0.28%) 
Gastrointestinal disorders   
Colitis ischaemic  1  1/351 (0.28%) 
General disorders   
Device breakage  1  1/351 (0.28%) 
Chest discomfort  1  1/351 (0.28%) 
Infections and infestations   
Pneumonia  1  4/351 (1.14%) 
Sepsis  1  1/351 (0.28%) 
Septic shock  1  1/351 (0.28%) 
Urosepsis  1  1/351 (0.28%) 
Diverticulitis  1  1/351 (0.28%) 
Injury, poisoning and procedural complications   
Hip fracture  1  2/351 (0.57%) 
Femur fracture  1  1/351 (0.28%) 
Joint dislocation  1  1/351 (0.28%) 
Fall  1  1/351 (0.28%) 
Musculoskeletal and connective tissue disorders   
Rheumatoid arthritis  1  2/351 (0.57%) 
Costochondritis  1  1/351 (0.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Breast cancer  1  1/351 (0.28%) 
Nervous system disorders   
VIIth nerve paralysis  1  1/351 (0.28%) 
Complex partial seizures  1  1/351 (0.28%) 
Convulsion  1  1/351 (0.28%) 
Renal and urinary disorders   
Nephrolithiasis  1  1/351 (0.28%) 
Reproductive system and breast disorders   
Menorrhagia  1  1/351 (0.28%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/351 (0.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Rituximab
Affected / at Risk (%)
Total   37/351 (10.54%) 
Infections and infestations   
Upper Respiratory Tract Infection  1  19/351 (5.41%) 
Nervous system disorders   
Headache  1  20/351 (5.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01382940     History of Changes
Other Study ID Numbers: ML25641
First Submitted: June 24, 2011
First Posted: June 27, 2011
Results First Submitted: January 6, 2014
Results First Posted: February 19, 2014
Last Update Posted: August 1, 2017