Clinical trial NCT01940094: The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach
Official title: The Assessment of Prednisone In Remission Trial (TAPIR) - Centers of Excellence Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Granulomatosis With Polyangiitis
Keywords: Granulomatosis with polyangiitis
Wegener's granulomatosis
WG
GPA
ANCA-Associated Vasculitis
AAV
Vasculitis
Prednisone
Glucocorticoid
Taper
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Office of Rare Diseases (ORD)
name: National Center for Advancing Translational Sciences (NCATS)
name: Rare Diseases Clinical Research Network
First posted: 2013-09-11
Enrollment: 159
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a multi-center randomized controlled trial to evaluate the effects of using low-dose prednisone as compared to stopping prednisone treatment entirely. Participants will be randomized 1:1 to taper their prednisone dose down to 5 mg/day or to 0 mg/day for the duration of the study (approximately six months) or until a study endpoint.

Detailed description: Patients with granulomatosis with polyangiitis (GPA, Wegener's) will be recruited at one of the Vasculitis Centers of Excellence. Participants will be randomized 1:1 either to taper their prednisone dose down to 5 mg/day according to a standardized schedule and stay at 5 mg/day of prednisone for the duration of the study or until a study endpoint, or taper their prednisone dose down to 0 mg/day using a standard schedule and stay at 0 mg/day for the duration of the study or until a study endpoint. All study participants will be followed for 6 months (from reaching a prednisone dose of 5 mg/day) or until an increase of prednisone dose (after randomization) occurs, whichever comes first.

Participants will have up to four study visits, a screening visit (visit 1), a baseline (visit 2), a month 3 visit (visit 3) and a month 6 or flare visit (visit 3) and up to two follow-up phone calls from the study coordinator at randomization and at month 1 (randomization and 1 month phone call may be combined if randomization occurs at month 1).

This study is a project of the Vasculitis Clinical Research Consortium (VCRC) funded through the National Institutes of Health Rare Diseases Clinical Research Network (RDCRN) with the purpose of promoting vasculitis research. The VCRC is the major clinical research infrastructure in North America for the study of vasculitis, and eight VCRC Centers of Excellence will be recruiting for this study.

Eligibility criteria: Inclusion Criteria:

1. Established diagnosis of granulomatosis with polyangiitis (GPA) where patients will need to meet at least 2 of the 5 for the classification of GPA, at least one of which must be criterion d or e:

   The modified American College of Rheumatology (ACR) criteria are:

   A. Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge.

   B. Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities.

   C. Active urinary sediment, defined as microscopic hematuria (\>5 red blood cells per high power field) or red blood cell casts.

   D. Granulomatosis inflammation on biopsy, defined as histologic changes showing granulomatous inflammation within the wall of an artery or in the perivascular or extravascular area. Note: Pauci-immune glomerulonephritis seen on kidney biopsy will suffice for this criterion.

   E. Positive anti-neutrophil cytoplasmic antibody (ANCA) test specific for proteinase-3 measures by enzyme-linked immunoassay.

   Patients who are myeloperoxidase (MPO) positive or ANCA negative are still eligible for this study if they meet the criteria above and are felt to have GPA.
2. Active disease within the prior 12 months (initial presentation or relapse) that at time of active disease required treatment with prednisone \>20 mg/day.
3. Disease remission at time of enrollment.
4. Prednisone dose at time of enrollment of ≥ 5 mg/day and ≤ 20 mg/day.
5. Participant age of 18 years or greater.
6. If the patient is taking an immunosuppressive medication agent other than prednisone (maintenance agent) then the maintenance agent must be at a stable dose for one month prior to enrollment with no plans by the treating physician to change the dose (other than for safety purposes/toxicity) for the duration of the study (through the month 6 visit or early termination). Acceptable maintenance agents include azathioprine, leflunomide, 6-mercaptopurine, methotrexate, mycophenolate mofetil, mycophenolate sodium, or rituximab. Patients may be on trimethoprim/sulfamethoxazole (TMP/SMX) for use as either a maintenance agent or for prophylaxis for infection. TMP/SMX may be used in combination with other drugs.

6.1 If the patient is regularly taking trimethoprim/sulfamethoxazole at any dose then the patient is eligible if there no plans by the treating physician to change the dose after enrollment (other than dose reduction or discontinuation for safety purposes/toxicity) for the duration of the study.

Exclusion Criteria:

1. Comorbid condition that has moderate likelihood of requiring a course of prednisone within one year of enrollment (e.g. chronic obstructive pulmonary disease (COPD), asthma, adrenal insufficiency).

Primary outcomes:
measure: Physician decision to increase glucocorticoids for disease relapse.
timeFrame: Six months
Secondary outcomes:
measure: Time to disease flare.
timeFrame: 6 months
measure: Safety outcomes.
timeFrame: 6 months
measure: Protocol performance at VCRC Centers of Excellence.
timeFrame: 6 months
measure: Health-related quality of life survey
timeFrame: Measured at baseline and end of the study
measure: Health-related quality of life surveys
timeFrame: Measured at baseline and the end of the study
measure: Health-related quality of life surveys
timeFrame: Measured at baseline, month 3, and end of the study
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: University of Pennsylvania
name: Peter A Merkel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Florida
name: Jeffery P Krischer, PhD
role: PRINCIPAL_INVESTIGATOR
References: