The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach (TAPIR)

• ClinicalTrials.gov Identifier: NCT01940094
• Recruitment Status: Recruiting
• First Posted: September 11, 2013
• Last Update Posted: October 12, 2022
• Sponsor: University of Pennsylvania
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Office of Rare Diseases (ORD); National Center for Advancing Translational Sciences (NCATS); Rare Diseases Clinical Research Network
• Information provided by (Responsible Party): Peter Merkel, University of Pennsylvania

Tracking Information

• First Submitted Date: September 6, 2013
• First Posted Date: September 11, 2013
• Last Update Posted Date: October 12, 2022
• Actual Study Start Date: February 2014
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 10, 2013): Physician decision to increase glucocorticoids for disease relapse. [ Time Frame: Six months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 3, 2013)

• Time to disease flare. [ Time Frame: 6 months ]
• Safety outcomes. [ Time Frame: 6 months ]
  Rate and type of serious adverse events and infections.
• Protocol performance at VCRC Centers of Excellence. [ Time Frame: 6 months ]
  Evaluation of patient characteristics, protocol compliance, participant retention, data completeness, timeliness of data entry, and data accuracy.
• Health-related quality of life survey [ Time Frame: Measured at baseline and end of the study ]
  Patient Reported Outcomes Measurement Information System (PROMIS) Assessment
• Health-related quality of life surveys [ Time Frame: Measured at baseline and the end of the study ]
  Measured by Short Form-36
• Health-related quality of life surveys [ Time Frame: Measured at baseline, month 3, and end of the study ]
  Measured by a Patient Global Assessment.

Original Secondary Outcome Measures (submitted: September 10, 2013)

• Time to disease flare. [ Time Frame: 6 months ]
• Health-related quality of life surveys. [ Time Frame: 6 months ]
  Measured by Short Form-36, PROMIS Assessment, and Patient Global Assessment.
• Safety outcomes. [ Time Frame: 6 months ]
  Rate and type of serious adverse events and infections.
• Protocol performance at VCRC Centers of Excellence. [ Time Frame: 6 months ]
  Evaluation of patient characteristics, protocol compliance, participant retention, data completeness, timeliness of data entry, and data accuracy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Granulomatosis With Polyangiitis

Intervention

• Drug: 5 mg Prednisone
  Subjects will remain on daily prednisone dose of 5 mg
  Other Names:

  • •5 mg/day glucocorticoids
  • •5 mg/day prednisone
  • •5 mg/day steroids
• Drug: 0 mg Prednisone
  Subjects will taper their prednisone dose from 5 mg per day to 0 mg per day

Study Arms

• Experimental: 5 mg Prednisone
  Subjects will be randomized to a prednisone dose of 5 mg per day for a 6 month period.
  Intervention: Drug: 5 mg Prednisone
• Experimental: 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.
  Intervention: Drug: 0 mg Prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 7, 2020): 159
• Original Estimated Enrollment (submitted: September 10, 2013): 60
• Estimated Study Completion Date: December 2023
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Carol McAlear, MA; cmcalear@upenn.edu

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01940094
• Other Study ID Numbers: VCRC5526A; R01HL115041 ( U.S. NIH Grant/Contract ); U54AR057319 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Peter Merkel, University of Pennsylvania
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Pennsylvania
• Original Study Sponsor: Same as current

Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Office of Rare Diseases (ORD)
• National Center for Advancing Translational Sciences (NCATS)
• Rare Diseases Clinical Research Network

Investigators

• Principal Investigator: Peter A Merkel, MD, MPH; University of Pennsylvania
• Principal Investigator: Jeffery P Krischer, PhD; University of South Florida

• PRS Account: University of Pennsylvania
• Verification Date: October 2022