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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Vasculitis; Granulomatosis With Polyangiitis; Wegener Granulomatosis
• Intervention / Treatment: Drug: 5 mg prednisone; Drug: 0 mg prednisone

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida TAPIR Study Team

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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:

   1. Nasal or oral inflammation, defined as the development of painful or painless oral ulcers or purulent or bloody nasal discharge
   2. Abnormal chest radiograph, defined as the presence of nodules, fixed infiltrates, or cavities.
   3. Active urinary sediment, defined as microscopic hematuria (>5 red blood cells per high power field) or red blood cell casts
   4. 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.
   5. 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 ≥ 5mg/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, 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.

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

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prednisone dose increase for disease relapse	Physician decision to increase prednisone dose for GPA disease relapse	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of disease flare sub types	Rates of GPA disease flare sub types: severe versus non-severe	6 months
Time to event flare	Time from randomization to GPA disease flare	6 months
Health related quality of life	Health related quality of life as assessed through the Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire	6 months
Safety Outcomes	Serious adverse events and infections	6 months
Protocol performance	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.	6 months

Collaborators and Investigators

• Sponsor: University of South Florida
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); National Institutes of Health (NIH); Rare Diseases Clinical Research Network; National Center for Advancing Translational Sciences (NCATS); Office of Rare Diseases (ORD)
• Investigators: Principal Investigator: Peter A Merkel, MD, MPH, University of Pennsylvania; Principal Investigator: Jeffrey P Krischer, PhD, University of South Florida

Publications and helpful links

General Publications

• Krischer J, Cronholm PF, Burroughs C, McAlear CA, Borchin R, Easley E, Davis T, Kullman J, Carette S, Khalidi N, Koening C, Langford CA, Monach P, Moreland L, Pagnoux C, Specks U, Sreih AG, Ytterberg S, Merkel PA; Vasculitis Clinical Research Consortium. Experience With Direct-to-Patient Recruitment for Enrollment Into a Clinical Trial in a Rare Disease: A Web-Based Study. J Med Internet Res. 2017 Feb 28;19(2):e50. doi: 10.2196/jmir.6798.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2014
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 28, 2013
• First Submitted That Met QC Criteria: August 28, 2013
• First Posted (Estimated): September 2, 2013

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases; Antineoplastic Agents; Glucocorticoids; Physiological Effects of Drugs; AAV; Pharmacologic Actions; ANCA-associated vasculitis; glucocorticoid; Therapeutic Uses; Hormones; Antineoplastic Agents, Hormonal; Anti-Inflammatory Agents; taper; Lung diseases; prednisone; vasculitis; GPA; WG; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Hormones, Hormone Substitutes, and Hormone Antagonists; Lung diseases, interstitial; Systemic Vasculitis; granulomatosis with polyangiitis; Wegeners'; Wegener Granulomatosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Respiratory Tract Diseases; Immune System Diseases; Autoimmune Diseases; Lung Diseases; Skin Diseases, Vascular; Lung Diseases, Interstitial; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vasculitis; Granulomatosis with Polyangiitis; Systemic Vasculitis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Glucocorticoids
• Other Study ID Numbers: VCRC 5526B TAPIR; R01HL115041 (U.S. NIH Grant/Contract); 5526B (Other Identifier: VCRC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No