Ignite Creation Date:
2024-05-05 @ 9:27 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001256
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Steroids and Methotrexate to Treat Systemic Vasculitis
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
An Open Trial of the Efficacy of Glucocorticoids and Methotrexate MTX in the Treatment of Systemic Vasculitis
Status:
COMPLETED
Status Verified Date:
2004-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will evaluate the safety and effectiveness of prednisone and methotrexate in treating severe Wegeners granulomatosis and other systemic vasculitides These diseases involve inflammation of blood vessels vasculitis that may affect the brain nerves eyes sinuses lungs kidneys intestinal tract skin joints heart and other sites Current treatment with prednisone and the anti-cancer drug cyclophosphamide is effective but has significant side effects and a high rate of disease recurrence In a small number of patients with vasculitis prednisone and methotrexate another anti-cancer drug have led to marked improvement with fewer side effects than are seen with cyclophosphamide This study will evaluate this drug combination in a larger patient population
Patients 10 to 80 years of age with active Wegeners granulomatosis polyarteritis nodosa Churg-Strauss vasculitis or microscopic polyangiitis overlap may be eligible for this 2 12 to 3-year study In addition patients with glomerulonephritis a type of kidney disease and a positive blood test for C-ANCA antibodies found in certain vasculitic kidney diseases or inflammatory sinusitis or lung nodule or infiltrates in the absence of infection may also be enrolled
Participants will take prednisone daily by mouth and low-dose methotrexate weekly by mouth or by injection either under the skin into a muscle or into a vein Patients who significantly improve with treatment will gradually reduce and eventually stop the prednisone If the remission lasts methotrexate will also be reduced and stopped after 2 12 years If active disease recurs the original treatment program may be started again Patients who never achieve complete remission with treatment but whose symptoms are well controlled and experience no serious side effects may choose to either continue low-dose methotrexate or stop therapy
Patients will be hospitalized 4 to 6 times a year about 2 to 8 days each time depending on their disease severity and response to illness In addition they will have the following tests and procedures
Medical history and physical examination upon admission to the study and then every 1 to 3 months
Blood tests for blood cell counts and for levels of enzymes that indicate liver damage upon admission then weekly and finally no less than monthly
Additional blood tests to measure blood chemistries and evaluate kidney function upon admission and again when clinically indicated
Chest X-rays upon admission and when clinically indicated
Computerized tomography CT and magnetic resonance imaging as needed
Electrocardiogram upon admission and then as clinically indicated
Lung function studies upon admission and at least every 6 months or as clinically indicated
Ear nose and throat evaluations as clinically indicated
Liver biopsy if blood tests to monitor liver function are persistently abnormal This procedure is done in the hospital under sedation to induce relaxation and drowsiness The skin over the liver upper right abdomen is numbed with a local anesthetic and a needle is passed rapidly in and out of the liver to collect a small tissue sample for microscopic examination
Patients 10 to 80 years of age with active Wegeners granulomatosis polyarteritis nodosa Churg-Strauss vasculitis or microscopic polyangiitis overlap may be eligible for this 2 12 to 3-year study In addition patients with glomerulonephritis a type of kidney disease and a positive blood test for C-ANCA antibodies found in certain vasculitic kidney diseases or inflammatory sinusitis or lung nodule or infiltrates in the absence of infection may also be enrolled
Participants will take prednisone daily by mouth and low-dose methotrexate weekly by mouth or by injection either under the skin into a muscle or into a vein Patients who significantly improve with treatment will gradually reduce and eventually stop the prednisone If the remission lasts methotrexate will also be reduced and stopped after 2 12 years If active disease recurs the original treatment program may be started again Patients who never achieve complete remission with treatment but whose symptoms are well controlled and experience no serious side effects may choose to either continue low-dose methotrexate or stop therapy
Patients will be hospitalized 4 to 6 times a year about 2 to 8 days each time depending on their disease severity and response to illness In addition they will have the following tests and procedures
Medical history and physical examination upon admission to the study and then every 1 to 3 months
Blood tests for blood cell counts and for levels of enzymes that indicate liver damage upon admission then weekly and finally no less than monthly
Additional blood tests to measure blood chemistries and evaluate kidney function upon admission and again when clinically indicated
Chest X-rays upon admission and when clinically indicated
Computerized tomography CT and magnetic resonance imaging as needed
Electrocardiogram upon admission and then as clinically indicated
Lung function studies upon admission and at least every 6 months or as clinically indicated
Ear nose and throat evaluations as clinically indicated
Liver biopsy if blood tests to monitor liver function are persistently abnormal This procedure is done in the hospital under sedation to induce relaxation and drowsiness The skin over the liver upper right abdomen is numbed with a local anesthetic and a needle is passed rapidly in and out of the liver to collect a small tissue sample for microscopic examination
Detailed Description:
Previous studies at the NIH have demonstrated that in over 90 of cases of Wegeners granulomatosis WG and other systemic necrotizing vasculitides glucocorticoid GC and daily low dose cyclophosphamide CP therapy has resulted in marked improvement and even remission However such therapy has been associated with about 50 relapses 10 resistance to initial treatment and significant toxicity in almost all patients Consequently we have attempted to identify alternative therapies for the systemic vasculitides that would be less toxic then daily CP An NIH study of the efficacy of intermittent high dose intravenous CP and daily GC Protocol 88-I-56 revealed that 79 of 14 patients with WG either failed to respond to treatment did not sustain improvement or could not tolerate continued treatment during a period of approximately two years In another study Protocol 89-I-18 we evaluated treatment with GC and weekly oral doses of methotrexate MTX in 15 patients with Takayasus arteritis in whom disease previously failed to be controlled with GC GC CP or in whom remission with such treatment was followed by relapse Fifty-three percent 815 of patients previously dependent on GC were able to achieve remission and discontinue GC therapy Five of seven patients who remained on GC were in remission and receiving at least 50 less GC than prior to MTX therapy Only three patients had progressive disease The mean follow-up period was 20 months We have also recently analyzed our results for MTX GC therapy and 29 patients with WG Seventy-six percent of patients had marked improvement and 69 achieved remission Seventy-two percent of those in remission have not required GC therapy for a mean period 10 months We conclude that weekly low dose MTX therapy is a feasible alternative to CP in the treatment of systemic vasculitis Judgement of the ultimate value of such therapy should be deferred until a greater number of patients have been studied over a longer period of time
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 90-I-0086 | None | None | None |