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

Primary Purpose

Granulomatosis With Polyangiitis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
5 mg Prednisone
0 mg Prednisone
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Granulomatosis With Polyangiitis focused on measuring Granulomatosis with polyangiitis, Wegener's granulomatosis, WG, GPA, ANCA-Associated Vasculitis, AAV, Vasculitis, Prednisone, Glucocorticoid, Taper

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • University of Kansas Medical Center
  • Brigham and Women's Hospital
  • Mayo Clinic
  • Cleveland Clinic
  • University of Pennsylvania
  • University of Pittsburgh
  • University of Utah
  • St. Joseph's Healthcare
  • Mount Sinai Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

5 mg Prednisone

0 mg Prednisone

Arm Description

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

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

Outcomes

Primary Outcome Measures

Physician decision to increase glucocorticoids for disease relapse.

Secondary Outcome Measures

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

Full Information

First Posted
September 6, 2013
Last Updated
October 13, 2023
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
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1. Study Identification

Unique Protocol Identification Number
NCT01940094
Brief Title
The Assessment of Prednisone In Remission Trial - Centers of Excellence Approach
Acronym
TAPIR
Official Title
The Assessment of Prednisone In Remission Trial (TAPIR) - Centers of Excellence Approach
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 2014 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the 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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granulomatosis With Polyangiitis
Keywords
Granulomatosis with polyangiitis, Wegener's granulomatosis, WG, GPA, ANCA-Associated Vasculitis, AAV, Vasculitis, Prednisone, Glucocorticoid, Taper

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
5 mg Prednisone
Arm Type
Experimental
Arm Description
Subjects will be randomized to a prednisone dose of 5 mg per day for a 6 month period.
Arm Title
0 mg Prednisone
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
5 mg Prednisone
Other Intervention Name(s)
•5 mg/day glucocorticoids, •5 mg/day prednisone, •5 mg/day steroids
Intervention Description
Subjects will remain on daily prednisone dose of 5 mg
Intervention Type
Drug
Intervention Name(s)
0 mg Prednisone
Intervention Description
Subjects will taper their prednisone dose from 5 mg per day to 0 mg per day
Primary Outcome Measure Information:
Title
Physician decision to increase glucocorticoids for disease relapse.
Time Frame
Six months
Secondary Outcome Measure Information:
Title
Time to disease flare.
Time Frame
6 months
Title
Safety outcomes.
Description
Rate and type of serious adverse events and infections.
Time Frame
6 months
Title
Protocol performance at VCRC Centers of Excellence.
Description
Evaluation of patient characteristics, protocol compliance, participant retention, data completeness, timeliness of data entry, and data accuracy.
Time Frame
6 months
Title
Health-related quality of life survey
Description
Patient Reported Outcomes Measurement Information System (PROMIS) Assessment
Time Frame
Measured at baseline and end of the study
Title
Health-related quality of life surveys
Description
Measured by Short Form-36
Time Frame
Measured at baseline and the end of the study
Title
Health-related quality of life surveys
Description
Measured by a Patient Global Assessment.
Time Frame
Measured at baseline, month 3, and end of the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Active disease within the prior 12 months (initial presentation or relapse) that at time of active disease required treatment with prednisone >20 mg/day. Disease remission at time of enrollment. Prednisone dose at time of enrollment of ≥ 5 mg/day and ≤ 20 mg/day. Participant age of 18 years or greater. 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter A Merkel, MD, MPH
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeffery P Krischer, PhD
Organizational Affiliation
University of South Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15261
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
St. Joseph's Healthcare
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Mount Sinai Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 3L9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://rarediseasesnetwork.org/cms/vcrc/
Description
Vasculitis Clinical Research Consortium

Learn more about this trial

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

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