Rituximab for the Treatment of Wegener's Granulomatosis and Microscopic Polyangiitis - Study Results

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

This study has been completed.

Study NCT00104299 Information provided by National Institute of Allergy and Infectious Diseases (NIAID)

First Received on February 24, 2005. Last Updated on July 27, 2011 History of Changes

Results First Received: February 2, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, 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	93 ^[1]	90 ^[1]
NOT COMPLETED	6	8
Adverse Event	2	1
Death	1	2
Withdrawal by Subject	2	5
Physician Decision	1	0

[1]	completed six months

Baseline Characteristics

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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.

Baseline Measures

	Rituximab	Control Group	Total
Number of Participants [units: participants]	99	98	197
Age [units: participants]
<=18 years	3	3	6
Between 18 and 65 years	60	76	136
>=65 years	36	19	55
Age [units: years] Mean ± Standard Deviation	54.0 ± 16.76	51.5 ± 14.07	52.8 ± 15.49
Gender [units: participants]
Female	52	45	97
Male	47	53	100
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
VDI ^[2] [units: score units] Mean ± Standard Deviation	1.4 ± 1.8	1.0 ± 1.4	1.2 ± 1.7

[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.
[2]	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.

[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.

[2]

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

1. Primary:

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

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2. Secondary:

Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy [ Time Frame: 18 months ]

Results not yet posted. Anticipated Posting Date: 12/2011 Safety Issue: Yes

Serious Adverse Events

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Other Adverse Events

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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.

Limitations and Caveats

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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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:

Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32.

Responsible Party:	Associate Director, Clinical Research Program, DAIT/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:	July 27, 2011
Health Authority:	United States: Food and Drug Administration