Jan 12, 2016

About GLORIA

 

The Glucocorticoid Low-dose Outcome in RheumatoId Arthritis Study (GLORIA)

Coordinator Center

VU University Medical Center

Funding

H2020 European Commission

Purpose

Comparing the cost-effectiveness and safety of additional low-dose glucocorticoid in treatment strategies for elderly patients with rheumatoid arthritis

Official Title

The Glucocorticoid Low-dose Outcome in RheumatoId Arthritis Study Comparing the Cost-effectiveness and Safety of Additional Low-dose Glucocorticoid in Treatment Strategies for Elderly Patients With Rheumatoid Arthritis

Study Type

Interventional

 

Study Design

Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

The GLORIA study is a randomized, double­blind, placebo-controlled pragmatic multicenter clinical trial to assess the effectiveness and safety of a daily dose of 5 mg prednisolone or matching placebo in elderly RA patients.

Patients will be randomized into two arms: the experimental arm (receiving prednisolone 5 mg/day) or the control arm (receiving placebo). Our design emulates the routine care setting: eligibility criteria are very liberal, assessments and procedures are tailored to represent standard of care, and concurrent antirheumatic treatment is allowed next to the trial medication with minimal limitations.

Furthermore, all patients will have an adherence monitoring device loaded into the cap of the drug bottle; adherence data will be monitored throughout the trial. In addition, to test the effect of adherence reminders, a substudy (another trial) will be nested in the main GLORIA trial.

 

Arms

Assigned Interventions

Experimental

Prednisolone 5 mg

1 capsule per day

Control

Placebo

1 capsule per day

 

The substudy is limited to patients with a smart device (smartphone, tablet, etc.) who have completed 3 months of the main study on treatment. The experimental arm of the substudy will receive an application loaded onto their smart device that communicates with an adherence monitoring device loaded into the cap of the drug bottle and delivers reminders to improve adherence. The control arm of the substudy will not have this application and reminders. The substudy has a duration of three months.
The primary objectives of the GLORIA study are:

 

a) To assess the effectiveness, safety and costeffectiveness of 2 years of low dose GC therapy (5 mg/day) compared to placebo as co­treatment for elderly RA patients in a pragmatic randomized trial


b) Study medication adherence through a medication packaging solution, and test the effectiveness of smart device technology to improve adherence

Deliver an outcome prediction model for individual patient outcome, to tailor treatment strategies for elderly RA patients with comorbidities. Deliver data to support:

 

1) better guidelines on RA treatment in the elderly;

 

2) more accurate information for elderly RA patients, their physicians and researchers;

 

3) improved strategies for trial design and conduct in the elderly.

 

Criteria

Population (base) RA patients of 65 years of age and older requiring antirheumatic therapy.

Inclusion criteria – In order to be eligible to participate in this study, a subject must meet all of the following criteria:

  1. RA according to the 2010 classification criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR);
  2. Inadequate disease control, as evidenced by a disease activity score of 28 joints calculated with erythrocyte sedimentation rate (DAS28) ≥3.20;
  3. age ≥ 65 years.

Exclusion criteria – A potential subject who meets any of the following criteria will be excluded from participation in this study:

 

Change, stop or start of antirheumatic treatment in the last three months prior to eligibility assessment, including methotrexate, sulfasalazine, hydroxychloroquine, leflunomide, azathioprine, intramuscular and oral gold, cyclosporine, biologic agents including antiTNF, anakinra, abatacept, rituximab, tocilizumab (temporary exclusion);

 

Treatment with systemic glucocorticoid (GC): oral or parenteral GC with a cumulative prednisolone equivalent dose of 200 mg or higher in the last 3 months;

 

Treatment with any GC (oral, intraarticular, intravenous or intramuscular) in the last 30 days (temporary exclusion);

 

Note: as this is a pragmatic trial, patients who require start of (other) anti-rheumatic treatment at baseline or during the trial can still be eligible

Exposure to investigational therapy in the last three months;

Current participation in another clinical trial;

 

Major surgery, donation or loss of approximately 500 ml blood within 4 weeks prior to the screening visit (temporary exclusion);

 

Absolute contraindication to low-dose prednisolone, as determined by the treating physician, such as: uncontrolled chronic infections, diabetes mellitus, hypertension, osteoporosis. When these conditions are under control (e.g. with anti-osteoporosis drugs, anti-hypertensive drugs) these patients can enter;

 

Absolute contraindication to Calcium and/or Vitamin D supplement as determined by the treating physician, such as: hyperparathyroidism (when insufficiently treated); Uncontrolled comorbid conditions, short life span, etc. as determined by the treating physician

 

Subjects/patients not capable or willing to provide informed consent

Substudy  

Additional exclusion criteria for subjects participating in the substudy to measure the effect of a reminder via smart device on adherence. Inability/difficulty to measure benefit:

  • Not in the possession of a smart device;
  • Premature discontinuation of study medication within or at 3 months of the main trial.

Primary Outcome Measures

  1. Signs and symptoms: the time-averaged mean value of the DAS28;
  2. The total number of patients experiencing at least one adverse event (AE) of Special Interest (an Serious Adverse Event (SAE), or an AE on a pre-specified list of clinically relevant AEs commonly associated with the disease and glucocorticoid use

Secondary Outcome Measures

  • Damage progression: 2-year change in total Sharp/van der Heijde damage score of hands and forefeet radiographs
  • WHO-ILAR core set of RA outcome measures
  • Severity and duration of morning stiffness
  • Severity and duration of fatigue due to RA
  • SF-36 – The Short Form 36-item Health Survey, a questionnaire about quality of life
  • RA Impact of Disease (RAID) tool – The RAID is a validated questionnaire assessing the seven most important domains of impact of RA on the patients
  • Health Assessment Questionnaire (HAQ)
  • Cost questionnaire, including Activity Limitation (part of cost questionnaire)and Work Disability (for those holding a paid job, part of cost questionnaire)
  • Utility/Quality-adjusted life years (QALY): EuroQoL in 5 dimensions (EQ-5D)
  • Vital signs (heart rate and blood pressure), height, weight, and abdominal circumference
  • Bone mass assessed by Dual-energy X-ray Absorptiometry (DXA)
  • Vertebral Fracture Analysis (by DXA OR lateral radiograph of thoracic and lumbar spine)
  • Discontinuation of study drug with reason: this includes patients in whom treatment with prednisolone becomes clinically indicated or those with unacceptable side effects attributable to study medication
  • Change of antirheumatic treatment, with reason
  • Intensification of treatment for existing comorbidity, e.g. hypertension ordiabetes
  • Joint replacement surgery
  • Cost-effectiveness and cost-utility: Estimate of costs of treatment and monitoring
  • Medication adherence: Adherence to trial drug is measured through the e-communicative packaging solution as the count of days in which the bottle is opened on the appropriate days, as measured by the adherence tool

Estimated Enrollment: 800 patients

Study Start Date: March 2016

Estimated Study Completion Date: August 2019

Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)

Methodology: The project is divided into 8 work packages (WP) (Table 1), which make up three work groups: Clinical Trial Workgroup, Data Translation Workgroup and Dissemination, Communication and Education Workgroup (Figure 1).

 

Trans-disciplinary approach of GLORIA project. Divided into different work groups: Clinical Trial Workgroup, Data Translation Workgroup and Dissemination, Communication and Education Workgroup. Additionally, project management is an important part of the GLORIA project.

Figure 1. Trans-disciplinary approach of GLORIA project. Divided into different work groups: Clinical Trial Workgroup, Data Translation Workgroup and Dissemination, Communication and Education Workgroup. Additionally, project management is an important part of the GLORIA project.

 

The main objectives of the GLORIA project per WP (copied from official pdf):

WP Objectives
1
  • Ensure that the project's main objectives are realized on schedule and within budgetary limits;
  • Ensure that the activities of all partners involved are in conformity with the EC contract and agreements.
2 Preparation of the pragmatic randomized clinical trial to provide evidence for the effective, safe and cost-effective use of chronic low-dose glucocorticoid therapy (GC) in elderby patients with rheumatoid arthritis (RA).
3 Pragmatic randomized clinical trial performed to provide evidence for the effective, safe and cost-effective use of chronic low-dose glucocorticoid therapy (GC) in elderly patients with rheumatoid arthritis (RA).
4
  • Clinical trial closure
  • Deliver a strong evidence base for the effective and safe use of low-dose GC therapy as co-treatment for elderly RA patients that improves outcome compared to the standard of care;
  • Demonstrate the cost-effectiveness of GC treatment for elderly patients through health technology assessment (HTA)

 
5
  • Deliver a medication packaging solution to measure medications adherence in elderly RS patients;
  • Test the effectiveness of smart device technologic to improve adherence

 
6 Deliver an outcome prediction model to determine individual patient outcome to tailor treatment strategies for elderly RA patients with comorbidities.
7

Deliver data to support:

  • Better guidelines on RA treatment in the elderly;
  • More accurate information for elderly RA patients, their prescribes and reseatchers;
  • Improved strategies for trial design and conduct in the elderly.

 
8
  • Ensure efficient and effective dissemination of the results to stakeholders and promote further uptake of the results via education activities.
(C) 2015 GLORIA