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CompletedNCT00104299RAVEUpdated Apr 21, 2017Results posted

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

A Phase 2/3 interventional study of Rituximab plus cyclophosphamide placebo (rituximab group) and Cyclophosphamide plus rituximab placebo (control group) in Vasculitis, Wegener's Granulomatosis and Microscopic Polyangiitis, sponsored by National Institute of Allergy and Infectious Diseases (NIAID). Completed at 8 sites in 2 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2017-04-21.

Sponsored by National Institute of Allergy and Infectious Diseases (NIAID) · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
197
Allocation
Randomized
Ages
15 Years and older
Sex
All
01

Study summary

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common type of small blood vessel inflammation in adults. ANCA-associated vasculitis includes Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Rituximab is a man-made antibody used to treat certain types of cancer. The purpose of this study is to determine the effectiveness of rituximab in treating patients with WG and MPA.

Study hypothesis: Rituximab is not inferior to conventional therapy in its ability to induce disease remission by Month 6.

Read the detailed description

Current conventional therapies for ANCA-associated vasculitis (AAV) are associated with high incidences of treatment failure, disease relapse, substantial toxicity, and patient morbidity and mortality. Rituximab is a monoclonal antibody used to treat non-Hodgkin's lymphoma. This study will evaluate the efficacy of rituximab with glucocorticoids in inducing disease remission in patients with severe forms of AAV (WG and MPA).

The study consists of two phases: a 6-month remission induction phase, followed by a 12-month remission maintenance phase. All participants will receive at least 1 g of pulse intravenous methylprednisolone or a dose-equivalent of another glucocorticoid preparation. Depending on the participant's condition, he or she may receive up to 3 days of intravenous methylprednisolone for a total of 3 g of methylprednisolone (or a dose-equivalent). During the remission induction phase, all participants will receive oral prednisone daily (1 mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6 study visit.

Next, participants will be randomly assigned to one of two arms. Arm 1 participants will receive rituximab (375 mg/m\^2) infusions once weekly for 4 weeks and cyclophosphamide (CYC) placebo daily for 3 to 6 months. Arm 2 participants will receive rituximab placebo infusions once weekly for 4 weeks and CYC daily for 3 to 6 months. During the remission maintenance phase, participants in Arm 1 will discontinue CYC placebo and start oral azathioprine (AZA) placebo daily until Month 18. Participants in Arm 2 will discontinue CYC and start AZA daily until Month 18. Participants who fail treatment before Month 6 will be crossed over to the other treatment arm unless there are specific contraindications. Participants in either group who reach clinical remission before they complete 6 months of therapy may switch from CYC/placebo to AZA/placebo if directed by their physicians.

All participants will be followed for at least 18 months. Initially, study visits are weekly, progressing to monthly and then quarterly visits as the study proceeds. Blood collection will occur at each study visit.

02

Conditions studied

  • Vasculitis
  • Wegener's Granulomatosis
  • Microscopic Polyangiitis

Keywords

  • ANCA
  • Vasculitis
  • Wegener's Granulomatosis
  • microscopic polyangiitis
  • ANCA-positive
  • ANCA-associated
  • ANCA-associated vasculitis
  • MPA
03

Who can participate

Ages eligible
15 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Weight of at least 88 pounds(40 kilograms)
  • Diagnosis of Wegener's granulomatosis or microscopic polyangiitis according to the definitions of the Chapel Hill Consensus Conference
  • Newly diagnosed patient of Wegener's granulomatosis or microscopic polyangiitis OR must be experiencing a disease flare characterized by: (a) active disease with a Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG) of 3 or greater that would normally require treatment with CYC; OR (b) disease severe enough to require treatment with CYC; OR (c) must be positive for either PR3-ANCA (ANCA directed against proteinase 3) or MPO-ANCA (ANCA directed against myeloperoxidase)at the screening
  • Willing to use acceptable forms of contraception for the duration of the study and for up to 1 year after stopping study medications
  • Willing to report pregnancies (female participants or male participants' partners) occurring at any time during the study and for up to 1 year after stopping study medications
  • Parent or guardian willing to provide informed consent, if applicable

Exclusion criteria

Exclusion Criteria:

  • Diagnosis of Churg-Strauss Syndrome according to the definitions of the Chapel Hill Consensus Conference
  • Have limited disease that would not normally be treated with CYC
  • Requires mechanical ventilation because of alveolar hemorrhage
  • History of severe allergic reactions to human or chimeric monoclonal antibodies
  • Active systemic infection
  • Have a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by pleural cavity or lung abscess, within 6 months prior to study entry
  • History of or current hepatitis B or C infection
  • HIV (human immunodeficiency virus) infected
  • Acute or chronic liver disease that, in the opinion of the investigator, may interfere with the study
  • History of or active cancer diagnosed within the last 5 years. Individuals with squamous cell or basal cell carcinomas of the skin and individuals with cervical carcinoma in situ who have received curative surgical treatment may be eligible for this study.
  • History of anti-glomerular basement membrane (anti-GBM) disease
  • Other uncontrolled disease, including drug and alcohol abuse, that may interfere with the study
  • Pregnancy or breastfeeding
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
197 participants (actual)

Study arms

  • Experimental
    Rituximab

    Drug: Rituximab plus cyclophosphamide placebo (rituximab group) · Drug: Methylprednisolone (or other glucocorticoid) · Drug: Prednisone

  • Active comparator
    Control Group

    Drug: Cyclophosphamide plus rituximab placebo (control group) · Drug: Azathioprine · Drug: Methylprednisolone (or other glucocorticoid) · Drug: Prednisone

Interventions

  • DrugRituximab plus cyclophosphamide placebo (rituximab group)

    375 mg/m\^2 infusions once weekly for 4 week

    Also known as: Rituxan

  • DrugCyclophosphamide plus rituximab placebo (control group)

    2 mg/kg/day orally for months 1-3

    Also known as: Cytoxan

  • DrugAzathioprine

    2 mg/kg/day orally for months 4-6

    Also known as: imuran

  • DrugMethylprednisolone (or other glucocorticoid)

    1 g/day intravenously for up to 3 days within 14 days prior to receiving rituximab

    Also known as: Medrol

  • DrugPrednisone

    During the remission induction phase, all participants will receive oral prednisone daily (1 mg/kg/day, not to exceed 80 mg/day). Prednisone tapering will be completed by the Month 6 study visit.

    Also known as: Deltasone, Liquid Pred, Meticorten, Orasone

05

What researchers measure

Primary outcomes

  1. Disease Remission

    A Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) score of 0 with prednisone taper successfully completed at six months. The BVAS/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.

    Time frame: 6 months post-randomization

Secondary outcomes

  1. Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy

    The adverse event rate for the following events considered related to vasculitis: Death; Grade 2 or higher leukopenia or thrombocytopenia; Grade 3 or higher infections; Hemorrhagic cystitis (grade 2 or lower needs confirmation by cytoscopy); Malignancy; Venous thromboembolic event (deep venous thrombosis or pulmonary embolism); Hospitalization resulting either from the disease or from a complication due to study treatment; Infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions (including cytokine release allergic reaction); Cerebrovascular accident

    Time frame: Through common close-out (defined as 18 months after the last participant is enrolled in the trial)

  2. Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization

    The 2-sided 95% CI of the percentage of participants who have a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and have successfully completed the glucocorticoid taper by 6 months post-randomization and the 2-sided 95% CI of the difference between two arms for assessing the superiority of rituximab to control \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

    Time frame: 6 months post-randomization

  3. The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

    Duration of complete remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of Prednisone to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

    Time frame: 18 months post-randomization

  4. The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

    Duration of remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of glucocorticoid by 6 months post-randomization to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing.

    Time frame: 18 months post-randomization

  5. Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups

    Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

    Time frame: 18 months post-randomization

  6. Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups

    Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and completing taper of glucocorticoid by 6 months post-randomization. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

    Time frame: 18 months post-randomization

06

Results

Posted Aug 25, 2011

Participant flow

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.

Participant flow — Overall Study
MilestoneRituximabControl Group
Started9998
Completed9088
Not completed910
Withdrew: Adverse event31
Withdrew: Death22
Withdrew: Withdrawal by subject26
Withdrew: Physician decision11
Withdrew: To have renal transplant10

Outcome measures

PrimaryDisease Remission

A Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) score of 0 with prednisone taper successfully completed at six months. The BVAS/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.

Time frame:
6 months post-randomization
Reported as:
Number · Participants
Disease Remission
ParticipantsRituximabControl Group
Disease Remission6352
Statistical analysis
  • Rituximab vs Control Group · 95.1% CI of difference · p = <0.001 (P-value is adjusted for interim analysis using a Lan-DeMets alpha spending function with an O'Brien-Fleming boundary, allocating 0.003 alpha to the interim analysis and 0.049 alpha to the final analysis.) · Difference between group success rates: 10.6 · 95.1% CI -3.2 to 24.3Calculate 95.1% CI around the difference in success rates between arms. Lower bound above non-inferiority margin of -20% indicates non-inferiority.
SecondaryRate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy

The adverse event rate for the following events considered related to vasculitis: Death; Grade 2 or higher leukopenia or thrombocytopenia; Grade 3 or higher infections; Hemorrhagic cystitis (grade 2 or lower needs confirmation by cytoscopy); Malignancy; Venous thromboembolic event (deep venous thrombosis or pulmonary embolism); Hospitalization resulting either from the disease or from a complication due to study treatment; Infusion reactions (within 24 hours of infusion) that result in the cessation of further infusions (including cytokine release allergic reaction); Cerebrovascular accident

Time frame:
Through common close-out (defined as 18 months after the last participant is enrolled in the trial)
Reported as:
Number · participants
Rate of Selected Adverse Events Experienced by Participants Receiving Rituximab Versus Those Receiving Conventional Therapy
participantsRituximabControl Group
Death22
Grade 2 or Higher Leukopenia723
Grade 2 or Higher Thrombocytopenia41
Grade 3 or Higher Infections1816
Hemorrhagic Cystitis (Grade 2 or Lower)21
Malignancy52
Venous Thromboembolic Event68
Hospitalization Resulting from the Disease167
Cerebrovascular Accident (CVA)11
Infusion Reactions Leading to Infusion Disc.10
Statistical analysis
  • Rituximab vs Control Group · Poisson regression model · p = 0.927 (P-value is from the Poisson regression model adjusting for clinical study site and ANCA type. The natural logarithm of participant-months is used as an offset in this model)
SecondaryPercentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization

The 2-sided 95% CI of the percentage of participants who have a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and have successfully completed the glucocorticoid taper by 6 months post-randomization and the 2-sided 95% CI of the difference between two arms for assessing the superiority of rituximab to control \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

Time frame:
6 months post-randomization
Reported as:
Number · participants
Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization
participantsRituximabControl Group
Percentage of Participants Who Have a BVAS/WG Score of 0 and Have Successfully Completed the Glucocorticoid Taper by 6 Months Post-randomization6251
Statistical analysis
  • Rituximab vs Control Group · Chi-squared · p = 0.133 · 95.1% confidence interval of difference: 10.6 · 95.1% CI -3.2 to 24.4At 6 months, the confidence interval is 95.1%.
SecondaryThe Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

Duration of complete remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of Prednisone to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

Time frame:
18 months post-randomization
Reported as:
Number · Days
The Duration of Complete Remission (BVAS=0, Off Glucocorticoids), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
DaysRituximabControl Group
25% Quartile (95%CI)243 (172 to NA)230 (145 to NA)
50% Quartile (95%CI)NA (NA to NA)NA (NA to NA)
75% Quartile (95%CI)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Rituximab vs Control Group · Log Rank · p = 0.761 (The log-rank test assesses the difference between the two treatment arms in the flaring pattern after complete remission) · Cox proportional hazard: 0.9 · 95% CI 0.5 to 1.7The log-rank test assesses the difference between the two treatment arms in the flaring pattern after complete remission
SecondaryThe Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups

Duration of remission is defined as a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and a completing taper of glucocorticoid by 6 months post-randomization to the first flare, BVAS/WG score of greater than 0, or an increase in Prednisone dosing.

Time frame:
18 months post-randomization
Reported as:
Number · Days
The Duration of Remission (BVAS=0), the Time to Limited and/or Severe Flare After Remission in the Two Treatment Groups
DaysRituximabControl Group
25% Quartile (95%CI)246 (152 to 335)168 (141 to 300)
50% Quartile (95%CI)NA (403 to NA)NA (353 to NA)
75% Quartile (95%CI)NA (NA to NA)NA (NA to NA)
Statistical analysis
  • Rituximab vs Control Group · Log Rank · p = 0.861 · Cox proportional hazard: 0.9 · 95% CI 0.6 to 1.5The log-rank test assesses the difference between the two treatment arms in the flaring pattern after remission
SecondaryTime to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups

Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

Time frame:
18 months post-randomization
Reported as:
Number · Days
Time to Remission (BVAS=0) From the Visit 1 Baseline Visit in the Two Treatment Groups
DaysRituximabControl Group
25% Quartile (95%CI)30 (29 to 34)29 (NA to NA)
50% Quartile (95%CI)57 (41 to 63)43 (30 to 58)
75% Quartile (95%CI)119 (69 to 123)112 (61 to 120)
Statistical analysis
  • Rituximab vs Control Group · Log Rank · p = 0.497 · Cox proportional hazard: 1.0 · 95% CI 0.7 to 1.3The hazard ratio and confidence interval are based on a Cox proportional hazard model comparing rituximab to the control group, adjusting for clinical study site, ANCA type, and glucocorticoid use prior to baseline.
SecondaryTime to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups

Time to complete remission is defined as the number of days from baseline visit (Visit 1) to a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG)\[1\] of 0 and completing taper of glucocorticoid by 6 months post-randomization. \[1\] The BVAS/WG is a disease activity index designed to document new or worsening clinically active vasculitis consisting of items divided into 9 organ based systems. BVAS/WG scores range from 0 to 63, with higher scores indicating more active disease

Time frame:
18 months post-randomization
Reported as:
Number · Days
Time to Complete Remission (BVAS=0, Off Glucocorticoids) From the Visit 1 Baseline Visit in the Two Treatment Groups
DaysRituximabControl Group
25% Quartile (95%CI)176 (173 to 177)177 (175 to 178)
50% Quartile (95%CI)180 (178 to 182)183 (180 to 187)
75% Quartile (95%CI)189 (183 to 253)266 (190 to 287)
Statistical analysis
  • Rituximab vs Control Group · Log Rank · p = 0.147 · Cox proportional hazard: 1.3 · 95% CI 0.9 to 1.8The hazard ratio and confidence interval are based on a Cox proportional hazard model comparing rituximab to the control group, adjusting for clinical study site, ANCA type, and glucocorticoid use prior to baseline.
Post-hocNumber of Subjects Experiencing Serious Adverse Events

Number of subjects according to originally received treatment that experienced a serious adverse event through 18 months post-randomization or prior to being censored from analyses due to crossover, switching to open-label treatment, or best medical judgment for censor. Events are categorized by coded system organ classes (SOC). Within each SOC, a participant was counted once if the participant reported one or more events coded to that SOC.

Time frame:
Randomization to censor at Crossover, Open-label or Best Medical Judgment (up to 18 months post-randomization)
Reported as:
Number · participants
Number of Subjects Experiencing Serious Adverse Events
participantsRituximabControl Group
# Participants with at least one SAE4237
Blood and Lymphatic System Disorders45
Cardiac Disorders22
Eye Disorders11
Gastrointestinal Disorders41
General Disorders and Administration Site53
Immune System Disorders22
Infections and Infestations1212
Injury, Poisoning, and Procedural Complications20
Investigations20
Metabolism and Nutrition Disorders22
Musculoskeletal and Connective Tissue Disorders23
Neoplasms Benign, Malignant, and Unspecified12
Nervous System Disorders10
Pregnancy, Puerperium, and Perinatal Conditions10
Psychiatric Disorders11
Renal and Urinary Disorders43
Respiratory, Thoracic, and Mediastinal Disorders88
Vascular Disorders17
Statistical analysis
  • Rituximab vs Control Group · Chi-squared · p = 0.504

Adverse events

Collected over From randomization through common close out (defined as 18 months after the last participant is enrolled in the trial). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Rituximab—60/99 (60.6%)97/99 (98%)
Control Group—47/98 (48%)97/98 (99%)
Most frequent serious events
Showing 10 of 113
Most frequent serious events
EventRituximabControl Group
PneumoniaInfections and infestations8/9910/98
Deep vein thrombosisVascular disorders1/998/98
Wegener's granulomatosisRespiratory, thoracic and mediastinal disorders8/994/98
AnaemiaBlood and lymphatic system disorders3/994/98
Renal failureRenal and urinary disorders4/992/98
Renal failure acuteRenal and urinary disorders2/993/98
LeukopeniaBlood and lymphatic system disorders3/990/98
Pulmonary embolismRespiratory, thoracic and mediastinal disorders3/992/98
Febrile neutropeniaBlood and lymphatic system disorders0/992/98
Pancreatitis acuteGastrointestinal disorders0/992/98
Most frequent other events
Showing 10 of 69
Most frequent other events
EventRituximabControl Group
LeukopeniaBlood and lymphatic system disorders13/9939/98
ArthralgiaMusculoskeletal and connective tissue disorders34/9924/98
CoughRespiratory, thoracic and mediastinal disorders32/9924/98
NauseaGastrointestinal disorders25/9931/98
FatigueGeneral disorders26/9930/98
Upper respiratory tract infectionInfections and infestations29/9924/98
HeadacheNervous system disorders28/9925/98
DiarrhoeaGastrointestinal disorders27/9920/98
RashSkin and subcutaneous tissue disorders14/9923/98
Alanine aminotransferase increasedInvestigations15/9922/98

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)RituximabControl GroupTotal
<=18 years336
Between 18 and 65 years6076136
>=65 years361955
Age, Continuous
Age, Continuous(years)RituximabControl GroupTotal
Mean54.0 ± 16.851.5 ± 14.152.8 ± 15.5
Sex: Female, Male
Sex: Female, Male(Participants)RituximabControl GroupTotal
Female524597
Male4753100
Region of Enrollment
Region of Enrollment(participants)RituximabControl GroupTotal
United States9190181
Netherlands8816
BVAS/WG
BVAS/WG(score units)RituximabControl GroupTotal
Mean8.1 ± 2.88.0 ± 3.48.0 ± 3.1
VDI
VDI(score units)RituximabControl GroupTotal
Mean1.4 ± 1.81.0 ± 1.41.2 ± 1.7
07

Study locations

8 sites
  • University of Alabama
    Birmingham, Alabama 35294, United States
  • Johns Hopkins University
    Baltimore, Maryland 21224, United States
  • Boston University
    Boston, Massachusetts 02118, United States
  • Mayo Clinic Foundation
    Rochester, Minnesota 55905, United States
  • Hospital for Special Surgery
    New York, New York 10128, United States
  • Duke University
    Durham, North Carolina 27710, United States
  • The Cleveland Clinic
    Cleveland, Ohio 44195, United States
  • University Hospital Groningen
    Groningen, 9713 GZ, Netherlands
08

References and documents

Publications

  • Zarin DA. Participant-level data and the new frontier in trial transparency. N Engl J Med. 2013 Aug 1;369(5):468-9. doi: 10.1056/NEJMe1307268. No abstract available. PubMed 23902488 ↗
  • 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. doi: 10.1056/NEJMoa0909905. PubMed 20647199 ↗
  • Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Fessler BJ, Ding L, Viviano L, Tchao NK, Phippard DJ, Asare AL, Lim N, Ikle D, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Mueller M, Sejismundo LP, Mieras K, Stone JH; RAVE-ITN Research Group. Efficacy of remission-induction regimens for ANCA-associated vasculitis. N Engl J Med. 2013 Aug 1;369(5):417-27. doi: 10.1056/NEJMoa1213277. PubMed 23902481 ↗
  • Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Viviano L, Ding L, Sejismundo LP, Mieras K, Ikle D, Jepson B, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Clinical outcomes of remission induction therapy for severe antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2013 Sep;65(9):2441-9. doi: 10.1002/art.38044. PubMed 23754238 ↗
  • Monach PA, Warner RL, Tomasson G, Specks U, Stone JH, Ding L, Fervenza FC, Fessler BJ, Hoffman GS, Ikle D, Kallenberg CG, Krischer J, Langford CA, Mueller M, Seo P, St Clair EW, Spiera R, Tchao N, Ytterberg SR, Johnson KJ, Merkel PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013 Aug;72(8):1342-50. doi: 10.1136/annrheumdis-2012-201981. Epub 2012 Sep 12. PubMed 22975753 ↗
  • Nasrallah M, Pouliot Y, Hartmann B, Dunn P, Thomson E, Wiser J, Butte AJ. Reanalysis of the Rituximab in ANCA-Associated Vasculitis trial identifies granulocyte subsets as a novel early marker of successful treatment. Arthritis Res Ther. 2015 Sep 21;17(1):262. doi: 10.1186/s13075-015-0778-z. PubMed 26387933 ↗
  • Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Ding L, Ikle D, Villareal M, Lim N, Brunetta P, Fervenza FC, Monach PA, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Outcomes of nonsevere relapses in antineutrophil cytoplasmic antibody-associated vasculitis treated with glucocorticoids. Arthritis Rheumatol. 2015 Jun;67(6):1629-36. doi: 10.1002/art.39104. PubMed 25776953 ↗
  • Miloslavsky EM, Specks U, Merkel PA, Seo P, Spiera R, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Tchao NK, Viviano L, Ding L, Ikle D, Villarreal M, Jepson B, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh K, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Stone JH; Rituximab in ANCA-Associated Vasculitis-Immune Tolerance Network Research Group. Rituximab for the treatment of relapses in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol. 2014 Nov;66(11):3151-9. doi: 10.1002/art.38788. PubMed 25047592 ↗
  • Berti A, Hillion S, Hummel AM, Son YM, Chriti N, Peikert T, Carmona EM, Abdulahad WH, Heeringa P, Harris KM, St Clair EW, Brunetta P, Fervenza FC, Langford CA, Kallenberg CG, Merkel PA, Monach PA, Seo P, Spiera RF, Stone JH, Grandi G, Sun J, Pers JO, Specks U, Cornec D; RAVE-ITN Research Group. Circulating autoreactive proteinase 3+ B cells and tolerance checkpoints in ANCA-associated vasculitis. JCI Insight. 2021 Nov 22;6(22):e150999. doi: 10.1172/jci.insight.150999. PubMed 34618687 ↗
  • Kronbichler A, Leierer J, Shin JI, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CGM, St Clair EW, Brunetta P, Fervenza FC, Geetha D, Keogh KA, Monach PA, Ytterberg SR, Mayer G, Specks U, Stone JH; RAVE-ITN Research Group. Association of Pulmonary Hemorrhage, Positive Proteinase 3, and Urinary Red Blood Cell Casts With Venous Thromboembolism in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Rheumatol. 2019 Nov;71(11):1888-1893. doi: 10.1002/art.41017. Epub 2019 Sep 25. PubMed 31216123 ↗
  • Wallace ZS, Miloslavsky EM, Cascino M, Unizony SH, Lu N, Hoffman GS, Kallenberg CGM, Langford CA, Merkel PA, Monach PA, Seo P, Spiera R, St Clair EW, Specks U, Brunetta P, Choi HK, Stone JH. Effect of Disease Activity, Glucocorticoid Exposure, and Rituximab on Body Composition During Induction Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. Arthritis Care Res (Hoboken). 2017 Jul;69(7):1004-1010. doi: 10.1002/acr.23099. PubMed 27696762 ↗
  • Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CM, St Clair EW, Ikle D, Tchao NK, Ding L, Brunetta P, Choi HK, Monach PA, Fervenza F, Stone JH, Specks U; RAVE-ITN Research Group. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis. 2016 Jun;75(6):1166-9. doi: 10.1136/annrheumdis-2015-208073. Epub 2015 Nov 30. PubMed 26621483 ↗

Individual participant data

Plan to share: Yes — Participant level data and additional relevant materials are available to the public in: 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal.

09

Registry details

Key details

Study ID
NCT00104299
Lead sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
Immune Tolerance Network (ITN), Genentech, Inc.
Responsible party
Sponsor
First posted
Feb 25, 2005
Start date
Jan 2005
Primary completion
Dec 2008
Completion
Jan 2010
Results posted
Aug 25, 2011
Last update
Apr 21, 2017

Study contacts

John H. Stone, MD, MPH
study chair · Johns Hopkins University
Ulrich Specks, MD
study chair · Mayo Clinic

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Mar 2017. You cannot join it, but the record below documents what was studied.

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