Clinical trial NCT01933724: The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach
Official title: The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: University of South Florida
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
name: Office of Rare Diseases (ORD)
name: National Center for Advancing Translational Sciences (NCATS)
name: Rare Diseases Clinical Research Network
First posted: 2013-09-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Prednisone dose increase for disease relapse
timeFrame: 6 months
Secondary outcomes:
measure: Rates of disease flare sub types
timeFrame: 6 months
measure: Time to event flare
timeFrame: 6 months
measure: Health related quality of life
timeFrame: 6 months
measure: Safety Outcomes
timeFrame: 6 months
measure: Protocol performance
timeFrame: 6 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: University of South Florida TAPIR Study Team
state: Florida
Study officials:
affiliation: University of Pennsylvania
name: Peter A Merkel, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of South Florida
name: Jeffrey P Krischer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.