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

NCT01933724 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: VCRC 5526B TAPIR5526BR01HL115041
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Granulomatosis With Polyangiitis; Wegener Granulomatosis; Vasculitis

Keywords

granulomatosis with polyangiitis; GPA; Wegeners'; WG; vasculitis; taper; prednisone; glucocorticoid; ANCA-associated vasculitis; AAV; Wegener Granulomatosis; Systemic Vasculitis; Lung diseases, interstitial; Lung diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Vascular Diseases; Cardiovascular Diseases; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Therapeutic Uses; Anti-Inflammatory Agents

Outcome Measures

Primary Outcomes (1)

• Prednisone dose increase for disease relapse

  Physician decision to increase prednisone dose for GPA disease relapse

  6 months

Secondary Outcomes (5)

• Rates of disease flare sub types

  6 months

• Time to event flare

  6 months

• Health related quality of life

  6 months

• Safety Outcomes

  6 months

• Protocol performance

  6 months

Study Arms (2)

5 mg prednisone

EXPERIMENTAL

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

Drug: 5 mg prednisone

0 mg prednisone

EXPERIMENTAL

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

Drug: 0 mg prednisone

Interventions

5 mg prednisone DRUG

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

Also known as: 5 mg glucocorticoids, 5 mg/day prednisone

5 mg prednisone

0 mg prednisone DRUG

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

Also known as: no prednisone, no glucocorticoids

0 mg prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• \. 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).

Sponsors & Collaborators

• University of South Florida: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator
• Office of Rare Diseases (ORD): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Rare Diseases Clinical Research Network: collaborator

Study Sites (1)

University of South Florida TAPIR Study Team

Tampa, Florida, 33612, United States

Location

Related Publications (2)

• 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.

  PMID: 28246067 RESULT

• 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.

  PMID: 39425055 DERIVED

MeSH Terms

Conditions

Granulomatosis with Polyangiitis; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Systemic Vasculitis; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Vascular Diseases; Cardiovascular Diseases

Interventions

Prednisone; Glucocorticoids

Condition Hierarchy (Ancestors)

Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Peter A Merkel, MD, MPH

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Jeffrey P Krischer, PhD

  University of South Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2013
• First Posted: September 2, 2013
• Study Start: February 17, 2014
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: July 29, 2024

Record last verified: 2024-07

Locations

US (1)