A Staged Therapeutic Approach Using Cyclophosphamide and Methotrexate in the Treatment of Wegener's Granulomatosis and Related Vasculitides
Data Collection
Autoimmune Diseases+15
+ Cardiovascular Diseases
+ Immune System Diseases
Summary
Study start date: March 1, 1995
Actual date on which the first participant was enrolled.The purpose of this study is to assess the efficacy and safety of a staged treatment regimen in Wegener's granulomatosis and related vasculitides in which patients will receive glucocorticoid plus cyclophosphamide at disease onset; cyclophosphamide will be switched to methotrexate upon disease remission. At the current time, cyclophosphamide plus glucocorticoids are the standard of care for the treatment of these disorders. Although this regimen has brought about a marked improvement in survival rate, it has been associated with significant toxicity. Methotrexate plus glucocorticoids have recently been investigated in patients with non life-threatening disease and while this regimen appears to have less toxicity than standard therapy it may be associated with a higher rate of disease relapse. By inducing patients with cyclophosphamide and glucocorticoids then switching to methotrexate at remission, we hope to combine the efficacy of cyclophosphamide with the more favorable toxicity profile of methotrexate. If successful, this regimen could provide a safer, yet effective therapeutic option which would be applicable to all patients regardless of disease severity. In this study, patients will be initially treated with cyclophosphamide and glucocorticoids and then switched from cyclophosphamide to methotrexate upon quiescence of disease activity. If at the end of two full years of methotrexate therapy there is continued evidence of disease remission, the drug will be tapered and ultimately discontinued. Patients will be prospectively monitored for evidence of disease activity 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 effects. This study will be open to patients with systemically active Wegener's granulomatosis or related vasculitis regardless of their degree of disease severity.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.100 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA: Documentation of WG based on clinical characteristics and histopathological evidence of vasculitis. Patients with a positive C- or P-ANCA and glomerulonephritis as evidence by the presence of red blood cell casts and proteinuria or renal biopsy showing necrotizing glomerulonephritis in the absence of positive immunofluorescence for immunoglobulin and complement 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 CTX 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. EXCLUSION CRITERIA: Evidence of active systemic infection which, in the judgement 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. Processes associated with an increased risk of MTX toxicity: 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. 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. Inability to comply with study guidelines.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, United StatesOpen National Institute of Allergy and Infectious Diseases (NIAID) in Google Maps