The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach

NCT ID: NCT01940094

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2024-12-31

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.

Conditions

Granulomatosis With Polyangiitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

5 mg Prednisone

Subjects will be randomized to a prednisone dose of 5 mg per day for a 6 month period.

Group Type: EXPERIMENTAL

5 mg Prednisone

Intervention Type: DRUG

Subjects will remain on daily prednisone dose of 5 mg

0 mg Prednisone

Subjects will be randomized to taper their prednisone dose from 5 mg per day to 0 mg per day for a 6 month period.

Group Type: EXPERIMENTAL

0 mg Prednisone

Intervention Type: DRUG

Subjects will taper their prednisone dose from 5 mg per day to 0 mg per day

Interventions

5 mg Prednisone

Subjects will remain on daily prednisone dose of 5 mg

Intervention Type: DRUG

0 mg Prednisone

Subjects will taper their prednisone dose from 5 mg per day to 0 mg per day

Intervention Type: DRUG

Other Intervention Names

•5 mg/day glucocorticoids; •5 mg/day prednisone; •5 mg/day steroids

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Office of Rare Diseases (ORD)

NIH

Sponsor Role: collaborator

National Center for Advancing Translational Sciences (NCATS)

NIH

Sponsor Role: collaborator

Rare Diseases Clinical Research Network

NETWORK

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Peter Merkel

Chief, Division of Rheumatology, Professor of Medicine and Epidemiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peter A Merkel, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Jeffery P Krischer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

University of Kansas Medical Center

Kansas City, Kansas, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Cleveland Clinic

Cleveland, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

University of Utah

Salt Lake City, Utah, United States

St. Joseph's Healthcare

Hamilton, Ontario, Canada

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Cronholm PF, Applequist J, Krischer J, Fontenot E, Davis T, Burroughs C, McAlear CA, Borchin R, Kullman J, Carette S, Khalidi N, Koening C, Langford CA, Monach P, Moreland L, Pagnoux C, Specks U, Sreih AG, Ytterberg SR, Merkel PA; Vasculitis Clinical Research Consortium. A study of implementation factors for a novel approach to clinical trials: constructs for consideration in the coordination of direct-to-patient online-based medical research. BMC Med Res Methodol. 2024 Oct 18;24(1):244. doi: 10.1186/s12874-024-02352-w.

Reference Type: DERIVED

PMID: 39425055 (View on PubMed)

Related Links

http://rarediseasesnetwork.org/cms/vcrc/

Vasculitis Clinical Research Consortium

Other Identifiers

R01HL115041

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U54AR057319

Identifier Type: NIH

Identifier Source: secondary_id

View Link

VCRC5526A

Identifier Type: -

Identifier Source: org_study_id