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Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis (RAVE)

This study has been completed.
Sponsor:
Collaborators:
Immune Tolerance Network (ITN)
Genentech, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00104299
First received: February 24, 2005
Last updated: March 23, 2017
Last verified: March 2017
Results First Received: February 2, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions: Vasculitis
Wegener's Granulomatosis
Microscopic Polyangiitis
Interventions: Drug: Rituximab plus cyclophosphamide placebo (rituximab group)
Drug: Cyclophosphamide plus rituximab placebo (control group)
Drug: Azathioprine
Drug: Methylprednisolone (or other glucocorticoid)
Drug: Prednisone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Eight centers in the United States and one center in the Netherlands (Groningen) enrolled 197 Antineutrophil cytoplasmic antibodies (ANCA)-positive patients with either Wegener’s granulomatosis or microscopic polyangiitis between December 30, 2004 and June 30, 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form.

Reporting Groups
  Description
Rituximab Participants received intravenous rituximab (Rituxan, Genentech) (at a dose of 375 mg per square meter of body-surface area once weekly for 4 weeks) plus daily placebo−cyclophosphamide. Refer to section titled “Detailed Description” for additional treatment information.
Control Group Participants received placebo−rituximab infusions plus daily cyclophosphamide (2 mg per kilogram of body weight, adjusted for renal insufficiency). Refer to section titled “Detailed Description” for additional treatment information.

Participant Flow:   Overall Study
    Rituximab   Control Group
STARTED   99   98 
COMPLETED   90 [1]   88 [1] 
NOT COMPLETED   9   10 
Adverse Event                3                1 
Death                2                2 
Withdrawal by Subject                2                6 
Physician Decision                1                1 
To have renal transplant                1                0 
[1] Number of participants who completed 18 months post-randomization



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rituximab Participants received intravenous rituximab (Rituxan, Genentech) (at a dose of 375 mg per square meter of body-surface area once weekly for 4 weeks) plus daily placebo−cyclophosphamide. Refer to section titled “Detailed Description” for additional treatment information.
Control Group Participants received placebo−rituximab infusions plus daily cyclophosphamide (2 mg per kilogram of body weight, adjusted for renal insufficiency). Refer to section titled “Detailed Description” for additional treatment information.
Total Total of all reporting groups

Baseline Measures
   Rituximab   Control Group   Total 
Overall Participants Analyzed 
[Units: Participants]
 99   98   197 
Age 
[Units: Participants]
Count of Participants
     
<=18 years      3   3.0%      3   3.1%      6   3.0% 
Between 18 and 65 years      60  60.6%      76  77.6%      136  69.0% 
>=65 years      36  36.4%      19  19.4%      55  27.9% 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.0  (16.8)   51.5  (14.1)   52.8  (15.5) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      52  52.5%      45  45.9%      97  49.2% 
Male      47  47.5%      53  54.1%      100  50.8% 
Region of Enrollment 
[Units: Participants]
     
United States   91   90   181 
Netherlands   8   8   16 
BVAS/WG [1] 
[Units: Score units]
Mean (Standard Deviation)
 8.1  (2.8)   8.0  (3.4)   8.0  (3.1) 
[1] The Birmingham Vasculitis Activity Score for Wegener’s Granulomatosis (WG) is a validated disease activity index. The BVAS/WG is designed to document new or worsening clinically active vasculitis and consists of a set of items divided into nine organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease. In this study, the primary end point was a BVAS/WG score of 0 and successful completion of the prednisone taper at 6 months.
VDI [1] 
[Units: Score units]
Mean (Standard Deviation)
 1.4  (1.8)   1.0  (1.4)   1.2  (1.7) 
[1] Vasculitis Damage Index. The VDI is a validated measure for damage assessment in vasculitis. The index comprises 64 items of damage (divided into 11 organ based systems) representative of damage incurred to patients with systemic vasculitis. Scores for this index range from 0 to 64, with higher scores indicating more severe damage.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Disease Remission   [ Time Frame: 6 months post-randomization ]

2.  Secondary:   Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy   [ Time Frame: Through common close-out (defined as 18 months after the last participant is enrolled in the trial) ]

3.  Secondary:   Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization   [ Time Frame: 6 months post-randomization ]

4.  Secondary:   The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups   [ Time Frame: 18 months post-randomization ]

5.  Secondary:   The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups   [ Time Frame: 18 months post-randomization ]

6.  Secondary:   Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups   [ Time Frame: 18 months post-randomization ]

7.  Secondary:   Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups   [ Time Frame: 18 months post-randomization ]

8.  Post-Hoc:   Number of Subjects Experiencing Serious Adverse Events   [ Time Frame: Randomization to censor at Crossover, Open-label or Best Medical Judgment (up to 18 months post-randomization) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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:  
Name/Title: Associate Director, Clinical Research Program
Organization: DAIT/NIAID
phone: (301) 594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov


Publications of Results:

Other Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00104299     History of Changes
Other Study ID Numbers: DAIT ITN021AI
Study First Received: February 24, 2005
Results First Received: February 2, 2011
Last Updated: March 23, 2017