The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach

Sponsor

University of South Florida (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01933724

Collaborator

National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH), Office of Rare Diseases (ORD) (NIH), National Center for Advancing Translational Science (NCATS) (NIH), Rare Diseases Clinical Research Network (Other)

Enrollment

Location

Arms

118.4

Anticipated Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized controlled trial in patients with a diagnosis of granulomatosis with polyangiitis (GPA; Wegener's)that are in remission to evaluate the effects of using low-dose glucocorticoids ( 5 mg/day of prednisone) as compared to stopping glucocorticoid treatment entirely (0 mg/day of prednisone)on rates of disease relapse/disease flares.

This study is a novel approach to conducting a randomized clinical trial in the community setting. This study is being conducted in parallel with a similar study at established vasculitis institutions. This study will have a patient centric approach to research in that subjects will be recruited online and through social media and vasculitis support networks. Participants will be consented online and will receive care through their regular treating physician so no travel or additional doctor visits are required. Study participants will consent to the study and complete online questionnaires about their prednisone dose and about how they are feeling.

Condition or Disease	Intervention/Treatment	Phase
Granulomatosis With Polyangiitis Wegener Granulomatosis Vasculitis	Drug: 5 mg prednisone Drug: 0 mg prednisone	Phase 3

Detailed Description

This open label pilot study will randomize 60 participants with GPA in remission affecting the sinonasal tract, oral mucosa, skin, musculoskeletal system, pulmonary parenchyma, or other disease features that warranted an administration of 20 mg/day or more within the last 12 months. At the time of enrollment, participants will need to be taking prednisone at a dose of ≥ 5mg/day and ≤ 20 mg/day. All enrolled participants will be instructed to reduce the daily dose of prednisone according to their treating physician. Once participants reach a prednisone dose of 5mg/day, they will be randomized at a 1:1 ratio to continue prednisone at 5 mg/day or to taper prednisone to 0 mg/day. Participants will be followed for approximately six months from reaching a prednisone dose of 5 mg/day.

The primary study outcome is the proportion of participants who increase prednisone for disease relapse within 6 months of randomization. Participant data collected via this study will be combined with that from a complementary study conducted at Vasculitis Clinical Research Consortium (VCRC) clinical centers.

Study Design

Study Type:

Interventional

Actual Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach

Actual Study Start Date :

Feb 17, 2014

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 5 mg prednisone Subjects will be randomized to 5 mg per day of prednisone for a 6 month period.	Drug: 5 mg prednisone Subjects will be randomized to take 5 mg per day of prednisone for a 6 month period. Other Names: 5 mg glucocorticoids 5 mg/day prednisone
Experimental: 0 mg prednisone Subjects will be randomized to 0 mg per day of prednisone dose for a 6 month period.	Drug: 0 mg prednisone Subjects will be randomized to taper their prednisone dose to no prednisone for a 6 month period. Other Names: no prednisone no glucocorticoids

Arm

Intervention/Treatment

Experimental: 5 mg prednisone

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

Drug: 5 mg prednisone

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

Other Names:

5 mg glucocorticoids

5 mg/day prednisone

Experimental: 0 mg prednisone

Subjects will be randomized to 0 mg per day of prednisone dose for a 6 month period.

Drug: 0 mg prednisone

Subjects will be randomized to taper their prednisone dose to no prednisone for a 6 month period.

Other Names:

no prednisone

no glucocorticoids

Outcome Measures

Primary Outcome Measures

Prednisone dose increase for disease relapse [6 months]
Physician decision to increase prednisone dose for GPA disease relapse

Secondary Outcome Measures

Rates of disease flare sub types [6 months]
Rates of GPA disease flare sub types: severe versus non-severe
Time to event flare [6 months]
Time from randomization to GPA disease flare
Health related quality of life [6 months]
Health related quality of life as assessed through the Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire
Safety Outcomes [6 months]
Serious adverse events and infections
Protocol performance [6 months]
Patient characteristics Protocol compliance This study is being conducted in parallel to a study at VCRC clinical centers. Protocol performance will be assessed through comparison of participant retention, data completeness, timeliness of data entry, and data accuracy between the two studies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Established diagnosis of granulomatosis with polyangiitis (GPA) (verified by medical record review by the Protocol Oversight Management Team) 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:

Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities.
Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per high power field) or red blood cell casts
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.
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 ≥ 5mg/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, rituximab, or mycophenolate sodium. 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 for dose reduction or discontinuation for safety purposes/toxicity) for the duration of the study.

Agreement from Treating Physician that 0mg/day of prednisone or 5mg/day of prednisone is standard of care
Participant's Treating Physician is located in the United States

Exclusion Criteria:

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).