VasculitisPhase 2NCT00004567
Comparison of Treatments to Maintain Disease Remission in Patients With Wegener's Granulomatosis and Related Vasculitis Syndromes
A Phase 2 study testing Mycophenolate Mofetil in people with Vasculitis and Wegener's Granulomatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This study will compare the safety and effectiveness of two drugs-methotrexate and mycophenolate mofetil (MPM)-in preventing disease recurrence in patients with Wegener's granulomatosis and related inflammatory blood vessel disorders. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Vasculitis, Wegener's Granulomatosis
- What is being tested?
- Mycophenolate Mofetil
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2000to Jun 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documentation of Wegener's granulomatosis (WG) or a related systemic vasculitis based on clinical characteristics and histopathologic and/or angiographic evidence of vasculitis. In the absence of histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the following criteria and in whom infectious and autoimmune diseases that may mimic WG or a related systemic vasculitides have been excluded will also be eligible:
- A positive assay for anti-neutrophil cytoplasmic autoantibodies (C- or P-ANCA) and the presence of glomerulonephritis defined by red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of immune deposits.
- A positive assay for anti-neutrophil cytoplasmic autoantibodies (C- or P-ANCA) and the presence of granulomatous inflammation on biopsy plus abnormal chest radiograph (defined as the presence of nodules, fixed infiltrates, or cavities) plus nasal/oral inflammation on clinical examination.
- Age 10-80 years.
- Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3 or if begun on CYC and glucocorticoid at an outside institution, a history of a Vasculitis Disease Activity Index greater than or equal to 3 at the time of therapy initiation.
Who cannot join
- Evidence of active infection which, in the judgment of the investigator, is of greater danger to the patient than the underlying vasculitis. In those instances in which infection cannot be ruled out by gram stain and culture of secretions or collections of fluid in involved organs, it may be necessary to obtain a biopsy of the affected tissue for microbiological and histopathological studies.
- Patients who are pregnant or who are nursing infants will not be eligible. Fertile women must have a negative pregnancy test within one week prior to study entry and must be using an effective means of birth control.
- Serological evidence of infection with human immunodeficiency virus, hepatitis C, or a positive hepatitis B surface antigen. A serological determination will be performed within two weeks of beginning study participation.
- Acute or chronic liver disease, past history of alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week), ongoing alcohol use of any volume that cannot be discontinued upon entry into the study.
- History of CYC- or methotrexate- induced pneumonitis with past treatment.
- Hypersensitivity to CYC, MPM, or methotrexate.
Show all 9Show fewer
- Transitional cell carcinoma of the bladder.
- Inability to comply with study guidelines.
- Hemocytopenia: platelet count less than 80,000/mm(3), leukocyte count less than 3,000/mm(3), hematocrit less than 20% (in the absence of gastrointestinal bleeding or hemolytic anemia).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
Official title: A Randomized Trial Comparing Methotrexate Versus Mycophenolate Mofetil for Remission Maintenance in Wegener's Granulomatosis and Related Vasculitides
This study will compare the safety and effectiveness of two drugs-methotrexate and mycophenolate mofetil (MPM)-in preventing disease recurrence in patients with Wegener's granulomatosis and related inflammatory blood vessel disorders. The standard treatment for these conditions is combination drug therapy with prednisone plus cyclophosphamide. However, although most patients improve on this therapy and achieve disease remission, many experience a relapse (return of the disease) some time after therapy is stopped. Also, these drugs can produce serious side effects during treatment. This study will test a new treatment regimen to try to maintain disease remission in these patients with minimal side effects.
Patients with Wegener's granulomatosis or other related blood vessel disorders between 10 and 80 years old will be considered for this study. All participants will start therapy with daily doses of prednisone and cyclophosphamide. Prednisone will be reduced gradually and then stopped after symptoms improve significantly. Cyclophosphamide will continue until the disease is in remission. Patients in remission will then be randomly assigned to continue treatment with either MPM or methotrexate. MPM is taken twice a day by mouth. Methotrexate is taken once a week, usually by mouth, but in some cases, by injection into a muscle or under the skin. Patients who do well and have no side effects will continue treatment for 2 years. Then, the drug will gradually be reduced (usually at monthly intervals) and finally stopped. No further treatment will be given unless a relapse occurs. At that time, the type of treatment will depend on various medical factors, including the severity of the recurrence and the patient's history of drug side effects.
Physical examinations and various tests, including blood and urine analyses, and X-rays, will be done periodically to evaluate the response to treatment and monitor drug side effects. The total duration of the study-from the screening evaluation through a 2-year follow up after all medications have been stopped-is about 5 to 6 years.
Read the detailed description
The purpose of this study is to assess the comparative efficacy of using methotrexate versus mycophenolate mofetil for maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis and related vasculitides. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will be randomized to receive either methotrexate or mycophenolate mofetil for remission maintenance. They will continue to receive the agent to which they are randomized for 2 years, after which time it will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events.
- Conditions
- Vasculitis, Wegener's Granulomatosis
- Being tested
- Mycophenolate Mofetil
- Keywords
- Relapse, Immunosuppressive, Toxicity, Purineantimetabolite, Alternative Agents, Wegener's Granulomatosis, Wegener's Disease, Blood Vessel Disorder, Systemic Vasculitis
- Medical subject headings
- Vasculitis, Granulomatosis with Polyangiitis, Recurrence, Vascular Diseases, Systemic Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2000 (estimated)
- Study startFeb 2000
- Study completionJun 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for VasculitisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 75 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004567
- Sponsor's protocol ID
- 000075
- Other IDs
- 00-I-0075
- Status last verified
- Jun 2004
- First submitted
- 11 Feb 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488-98. doi: 10.7326/0003-4819-116-6-488.
PubMed 1739240Nolle B, Specks U, Ludemann J, Rohrbach MS, DeRemee RA, Gross WL. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28-40. doi: 10.7326/0003-4819-111-1-28.
PubMed 2660645Jennette JC. Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Am J Kidney Dis. 1991 Aug;18(2):164-70. doi: 10.1016/s0272-6386(12)80874-2.
PubMed 1867173
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial Comparing Methotrexate Versus Mycophenolate Mofetil for Remission Maintenance in Wegener's Granulomatosis and Related Vasculitides
- ClinicalTrials.gov ID
- NCT00004567
- Acronym / sponsor ID
- 000075
- Conditions
- Vasculitis, Wegener's Granulomatosis
- Keywords
- Relapse, Immunosuppressive, Toxicity, Purineantimetabolite, Alternative Agents, Wegener's Granulomatosis, Wegener's Disease, Blood Vessel Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Feb 2000
- Study completion
- Jun 2004
- First posted
- 14 Feb 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will compare the safety and effectiveness of two drugs-methotrexate and mycophenolate mofetil (MPM)-in preventing disease recurrence in patients with Wegener's granulomatosis and related inflammatory blood vessel disorders. The standard treatment for these conditions is combination drug therapy with prednisone plus cyclophosphamide. However, although most patients improve on this therapy and achieve disease remission, many experience a relapse (return of the disease) some time after therapy is stopped. Also, these drugs can produce serious side effects during treatment. This study will test a new treatment regimen to try to maintain disease remission in these patients with minimal side effects.
Patients with Wegener's granulomatosis or other related blood vessel disorders between 10 and 80 years old will be considered for this study. All participants will start therapy with daily doses of prednisone and cyclophosphamide. Prednisone will be reduced gradually and then stopped after symptoms improve significantly. Cyclophosphamide will continue until the disease is in remission. Patients in remission will then be randomly assigned to continue treatment with either MPM or methotrexate. MPM is taken twice a day by mouth. Methotrexate is taken once a week, usually by mouth, but in some cases, by injection into a muscle or under the skin. Patients who do well and have no side effects will continue treatment for 2 years. Then, the drug will gradually be reduced (usually at monthly intervals) and finally stopped. No further treatment will be given unless a relapse occurs. At that time, the type of treatment will depend on various medical factors, including the severity of the recurrence and the patient's history of drug side effects.
Physical examinations and various tests, including blood and urine analyses, and X-rays, will be done periodically to evaluate the response to treatment and monitor drug side effects. The total duration of the study-from the screening evaluation through a 2-year follow up after all medications have been stopped-is about 5 to 6 years.
Detailed description
The purpose of this study is to assess the comparative efficacy of using methotrexate versus mycophenolate mofetil for maintaining remission that has been induced by cyclophosphamide and glucocorticoids in patients with Wegener's granulomatosis and related vasculitides. In this study, all patients will initially receive daily cyclophosphamide and glucocorticoids and then at disease remission, cyclophosphamide will be discontinued and patients will be randomized to receive either methotrexate or mycophenolate mofetil for remission maintenance. They will continue to receive the agent to which they are randomized for 2 years, after which time it will be tapered and discontinued. Patients will be prospectively monitored for evidence of disease relapse and drug toxicity. Specific parameters that will be obtained include the time to disease remission, the rate and time of disease relapse, and the incidence of drug-related adverse events.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Documentation of Wegener's granulomatosis (WG) or a related systemic vasculitis based on clinical characteristics and histopathologic and/or angiographic evidence of vasculitis. In the absence of histopathologic and/or angiographic evidence of vasculitis, patients who meet one of the following criteria and in whom infectious and autoimmune diseases that may mimic WG or a related systemic vasculitides have been excluded will also be eligible:
- Age 10-80 years.
- Evidence of active disease as defined by a Vasculitis Disease Activity Index of greater than or equal to 3 or if begun on CYC and glucocorticoid at an outside institution, a history of a Vasculitis Disease Activity Index greater than or equal to 3 at the time of therapy initiation.
Key exclusion criteria (9 listed)
- Evidence of active infection which, in the judgment of the investigator, is of greater danger to the patient than the underlying vasculitis. In those instances in which infection cannot be ruled out by gram stain and culture of secretions or collections of fluid in involved organs, it may be necessary to obtain a biopsy of the affected tissue for microbiological and histopathological studies.
- Patients who are pregnant or who are nursing infants will not be eligible. Fertile women must have a negative pregnancy test within one week prior to study entry and must be using an effective means of birth control.
- Serological evidence of infection with human immunodeficiency virus, hepatitis C, or a positive hepatitis B surface antigen. A serological determination will be performed within two weeks of beginning study participation.
- Acute or chronic liver disease, past history of alcohol abuse (greater than 14 oz of 100 proof liquor or equivalent per week), ongoing alcohol use of any volume that cannot be discontinued upon entry into the study.
- History of CYC- or methotrexate- induced pneumonitis with past treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mycophenolate Mofetil | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 1739240Hoffman GS, Kerr GS, Leavitt RY, Hallahan CW, Lebovics RS, Travis WD, Rottem M, Fauci AS. Wegener granulomatosis: an analysis of 158 patients. Ann Intern Med. 1992 Mar 15;116(6):488-98. doi: 10.7326/0003-4819-116-6-488.
- Background: PubMed 2660645Nolle B, Specks U, Ludemann J, Rohrbach MS, DeRemee RA, Gross WL. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28-40. doi: 10.7326/0003-4819-111-1-28.
- Background: PubMed 1867173Jennette JC. Antineutrophil cytoplasmic autoantibody-associated diseases: a pathologist's perspective. Am J Kidney Dis. 1991 Aug;18(2):164-70. doi: 10.1016/s0272-6386(12)80874-2.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mycophenolate Mofetil in people with Vasculitis and Wegener's Granulomatosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00004567, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.