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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University of South Florida
Sponsor:
Collaborators:
Rare Diseases Clinical Research Network
Information provided by (Responsible Party):
University of South Florida
ClinicalTrials.gov Identifier:
NCT01933724
First received: August 28, 2013
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

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 Intervention
Granulomatosis With Polyangiitis
Wegener Granulomatosis
Vasculitis
Drug: 5 mg prednisone
Drug: 0 mg prednisone

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Assessment of Prednisone In Remission Trial (TAPIR) - Patient Centric Approach

Resource links provided by NLM:


Further study details as provided by University of South Florida:

Primary Outcome Measures:
  • Prednisone dose increase for disease relapse [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Physician decision to increase prednisone dose for GPA disease relapse


Secondary Outcome Measures:
  • Rates of disease flare sub types [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Rates of GPA disease flare sub types: severe versus non-severe

  • Time to event flare [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Time from randomization to GPA disease flare

  • Health related quality of life [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Health related quality of life as assessed through the Patient Reported Outcomes Measurement Information System (PROMIS) questionnaire

  • Safety Outcomes [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Serious adverse events and infections

  • Protocol performance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    • 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.


Estimated Enrollment: 60
Study Start Date: February 2014
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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 ≤ 10 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  2. 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.
  3. Active disease within the prior 12 months (initial presentation or relapse) that at time of active disease required treatment with prednisone >20 mg/day (verified by medical record review by the Protocol Oversight Management Team)
  4. Disease remission at time of enrollment (verified by medical record review by the Protocol Oversight Management Team)
  5. Prednisone dose at time of enrollment of ≥ 5mg/day and ≤ 10 mg/day
  6. Participant age of 18 years or greater
  7. 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, 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.

    7.1 Rituximab is an acceptable maintenance agent if the last dose was given at least one month prior to enrollment and no additional doses are planned) for the duration of the study (through the month 6 visit or early termination). If a patient received rituximab and was then prescribed another maintenance agent, the patient is eligible if there are no plans by the treating physician to change the dose of the maintenance (other than for safety purposes/toxicity) for the duration of the study (through the month 6 visit or early termination).

    7.2 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.

  8. Agreement from Treating Physician that 0mg/day of prednisone or 5mg/day of prednisone is standard of care
  9. 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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01933724

Contacts
Contact: Jeffrey Krischer, PhD 1-888-443-1793 TAPIR@epi.usf.edu

Locations
United States, Florida
University of South Florida TAPIR Study Team Recruiting
Tampa, Florida, United States, 33612
Contact: Cristina Burroughs    888-443-1793    TAPIR@epi.usf.edu   
Principal Investigator: Jeffrey Krischer, PhD         
Sponsors and Collaborators
University of South Florida
Rare Diseases Clinical Research Network
Investigators
Principal Investigator: Peter A Merkel, MD, MPH University of Pennsylvania
Principal Investigator: Jeffrey P Krischer, PhD University of South Florida
  More Information

Additional Information:
No publications provided

Responsible Party: University of South Florida
ClinicalTrials.gov Identifier: NCT01933724     History of Changes
Other Study ID Numbers: VCRC 5526B TAPIR, 5526B, R01HL115041
Study First Received: August 28, 2013
Last Updated: May 30, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Federal Government
United States: Institutional Review Board

Keywords provided by University of South Florida:
vasculitis
ANCA-associated vasculitis
Systemic Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vasculitis
granulomatosis with polyangiitis
GPA
Wegeners'
WG
taper
prednisone
glucocorticoid
AAV
Wegener Granulomatosis
Lung diseases, interstitial
Lung diseases
Respiratory Tract Diseases
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

Additional relevant MeSH terms:
Vasculitis
Systemic Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Wegener Granulomatosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Glucocorticoids
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014