The Glucocorticoid Low-dose Outcome in RheumatoId Arthritis Study

NCT02585258 | Completed Phase 4 Results

• 1 other identifier: VUMC-ARC-GLORIA
• Study Type: interventional
• Target: 451
• Locations: 7 countries
• Sites: 28

Brief Summary

Comparing the cost-effectiveness and safety of additional low-dose glucocorticoid in treatment strategies for elderly patients with rheumatoid arthritis: The Glucocorticoid Low-dose Outcome in RheumatoId Arthritis Study (GLORIA)

Conditions

RheumatoId Arthritis

Outcome Measures

Primary Outcomes (2)

• Signs and Symptoms: Mean DAS28 Post Baseline

  mean of the DAS28 (disease activity score-28 joints) post baseline. Range 0-8, higher scores mean more disease activity. See link in reference list.

  0,3,6,12,18,24 months

• The Total Number of Patients Experiencing at Least One Adverse Event (AE) of Special Interest (AESI)

  AESI: (a serious adverse event \[SAE\], or an AE on a prespecified list of clinically relevant AEs commonly associated with the disease and glucocorticoid use

  24 months

Secondary Outcomes (1)

• Joint Damage Progression

  0, 24 months

Study Arms (2)

prednisolone

EXPERIMENTAL

prednisolone 5 mg per day

Drug: Prednisolone

placebo

PLACEBO COMPARATOR

placebo capsules once per day

Drug: Placebo

Interventions

Prednisolone DRUG

1 capsule containing a tablet of 5 mg prednisolone/ day

Also known as: glucocorticoid

prednisolone

Placebo DRUG

1 capsule containing a placebo tablet / day

Also known as: matching placebo

placebo

Eligibility Criteria

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

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• RA according to the 1987 or the 2010 classification criteria of the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) (Aletaha D et al, Ann Rheum Dis 2010;69:1580);
• inadequate disease control, as evidenced by a disease activity score of 28 joints calculated with erythrocyte sedimentation rate (DAS28) ≥2.60;
• age ≥ 65 years.

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Lower probability of benefit:
• Treatment with systemic GC: oral or parenteral GC with a cumulative prednisolone equivalent dose of 200 mg or higher in the last 3 months;
• Note: as this is a pragmatic trial, patients who require start of (other) antirheumatic treatment at baseline or during the trial can still be eligible (see 7.1).
• Higher probability of harm:
• Exposure to investigational therapy in the last three months;
• Current participation in another clinical trial;
• 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 antiosteoporosis drugs, antihypertensive 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.
• Difficulty to measure harm/benefit:
• Absolute indication to start with oral or intravenous GC, according to the treating physician;
• Inability to comply with medical instructions or inability to assess major outcomes at 6-monthly visits, in the assessment of the treating physician.
• Subjects/patients not capable or willing to provide informed consent.
• Substudy

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• European Commission: collaborator

Study Sites (28)

Charite

Berlin, Germany

Location

Facharztpraxis

Magdeburg, Germany

Location

Knappschaftsklinikum Saar

Püttlingen, Germany

Location

University of Debrecen

Debrecen, Hungary

Location

University of Genova

Genova, Italy

Location

Noordwest Ziekenhuis

Alkmaar, Netherlands

Location

Meander

Amersfoort, Netherlands

Location

VUmc

Amsterdam, Netherlands

Location

Gelre

Apeldoorn, Netherlands

Location

Groene Hart Ziekenhuis

Gouda, Netherlands

Location

UMCG

Groningen, Netherlands

Location

MCL

Leeuwarden, Netherlands

Location

LUMC

Leiden, Netherlands

Location

MC Zuiderzee

Lelystad, Netherlands

Location

MUMC

Maastricht, Netherlands

Location

Maasstad

Rotterdam, Netherlands

Location

Antonius Ziekenhuis

Sneek, Netherlands

Location

HAGA

The Hague, Netherlands

Location

UMC Utrecht

Utrecht, Netherlands

Location

VieCurie MC

Venlo, Netherlands

Location

CHU Coimbra

Coimbra, Portugal

Location

Hospital de Egas Moniz

Lisbon, Portugal

Location

Hospital de Santa Maria

Lisbon, Portugal

Location

Instituto Portugues de Reumatologia

Lisbon, Portugal

Location

Hospital de Ponte Lima

Ponte de Lima, Portugal

Location

Carol Davila University of Medicine and Pharmacy

Bucharest, Romania

Location

Carol Davila

Bucharest, Romania

Location

NURCH

Bratislava, Slovakia

Location

Related Publications (17)

• Palmowski Y, Buttgereit T, Dejaco C, Bijlsma JW, Matteson EL, Voshaar M, Boers M, Buttgereit F. "Official View" on Glucocorticoids in Rheumatoid Arthritis: A Systematic Review of International Guidelines and Consensus Statements. Arthritis Care Res (Hoboken). 2017 Aug;69(8):1134-1141. doi: 10.1002/acr.23185. Epub 2017 Jul 10.

  PMID: 28029750 BACKGROUND

• Palmowski Y, Buttgereit F, Boers M. Reply. Arthritis Care Res (Hoboken). 2019 Apr;71(4):577-578. doi: 10.1002/acr.23452. No abstract available.

  PMID: 29073333 BACKGROUND

• Hartman L, Rasch LA, Klausch T, Bijlsma HWJ, Christensen R, Smulders YM, Ralston SH, Buttgereit F, Cutolo M, Da Silva JAP, Opris D, Rovensky J, Szamosi S, Middelink LM, Lems WF, Boers M. Harm, benefit and costs associated with low-dose glucocorticoids added to the treatment strategies for rheumatoid arthritis in elderly patients (GLORIA trial): study protocol for a randomised controlled trial. Trials. 2018 Jan 25;19(1):67. doi: 10.1186/s13063-017-2396-3.

  PMID: 29370811 BACKGROUND

• Hartman L, Lems WF, Boers M. Outcome measures for adherence data from a medication event monitoring system: A literature review. J Clin Pharm Ther. 2019 Feb;44(1):1-5. doi: 10.1111/jcpt.12757. Epub 2018 Sep 1.

  PMID: 30171815 BACKGROUND

• Hartman L, Cutolo M, Bos R, Opris-Belinski D, Kok MR, Griep-Wentink HJRM, Klaasen R, Allaart CF, Bruyn GAW, Raterman HG, Voshaar MJH, Gomes N, Pinto RMA, Klausch LT, Lems WF, Boers M. Medication adherence in older people with rheumatoid arthritis is lower according to electronic monitoring than according to pill count. Rheumatology (Oxford). 2021 Nov 3;60(11):5239-5246. doi: 10.1093/rheumatology/keab207.

  PMID: 33682887 BACKGROUND

• Palmowski A, Nielsen SM, Buttgereit T, Palmowski Y, Boers M, Christensen R, Buttgereit F. Association Between Participant Retention and the Proportion of Included Elderly People in Rheumatology Trials: Results From a Series of Exploratory Meta-Regression Analyses. Arthritis Care Res (Hoboken). 2020 Oct;72(10):1490-1496. doi: 10.1002/acr.24051.

  PMID: 31421022 BACKGROUND

• Palmowski A, Buttgereit T, Palmowski Y, Nielsen SM, Boers M, Christensen R, Buttgereit F. Applicability of trials in rheumatoid arthritis and osteoarthritis: A systematic review and meta-analysis of trial populations showing adequate proportion of women, but underrepresentation of elderly people. Semin Arthritis Rheum. 2019 Jun;48(6):983-989. doi: 10.1016/j.semarthrit.2018.10.017. Epub 2018 Nov 2.

  PMID: 30466715 BACKGROUND

• Palmowski A, Nielsen SM, Buttgereit T, Palmowski Y, Boers M, Christensen R, Buttgereit F. Glucocorticoid-trials in rheumatoid arthritis mostly study representative real-world patients: A systematic review and meta-analysis. Semin Arthritis Rheum. 2020 Dec;50(6):1400-1405. doi: 10.1016/j.semarthrit.2020.02.016. Epub 2020 Mar 2.

  PMID: 32222381 BACKGROUND

• Forsat ND, Palmowski A, Palmowski Y, Boers M, Buttgereit F. Recruitment and Retention of Older People in Clinical Research: A Systematic Literature Review. J Am Geriatr Soc. 2020 Dec;68(12):2955-2963. doi: 10.1111/jgs.16875. Epub 2020 Oct 19.

  PMID: 33075140 BACKGROUND

• Buttgereit T, Palmowski A, Forsat N, Boers M, Witham MD, Rodondi N, Moutzouri E, Navidad AJQ, Van't Hof AWJ, van der Worp B, Coll-Planas L, Voshaar M, de Wit M, da Silva J, Stegemann S, Bijlsma JW, Koeller M, Mooijaart S, Kearney PM, Buttgereit F. Barriers and potential solutions in the recruitment and retention of older patients in clinical trials-lessons learned from six large multicentre randomized controlled trials. Age Ageing. 2021 Nov 10;50(6):1988-1996. doi: 10.1093/ageing/afab147.

  PMID: 34324628 BACKGROUND

• Santiago T, Voshaar M, de Wit M, Carvalho PD, Buttgereit F, Cutolo M, Paolino S, Castelar Pinheiro GR, Boers M, Da Silva JAP. Patients' and rheumatologists' perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis-an international survey within the GLORIA study. Rheumatology (Oxford). 2021 Jul 1;60(7):3334-3342. doi: 10.1093/rheumatology/keaa785.

  PMID: 33394036 BACKGROUND

• van der Heijde DM, van Leeuwen MA, van Riel PL, van de Putte LB. Radiographic progression on radiographs of hands and feet during the first 3 years of rheumatoid arthritis measured according to Sharp's method (van der Heijde modification). J Rheumatol. 1995 Sep;22(9):1792-6.

  PMID: 8523365 BACKGROUND

• Hartman L, Bos R, Buttgereit F, Guler-Yuksel M, Ionescu R, Kok MR, Lems WF, Micaelo M, Opris-Belinski D, Pusztai A, Santos E, Da Silva J, Szekanecz Z, Zeiner K, Zhang D, Boers M. Remarkable international variability in reasons for ineligibility and non-participation in the GLORIA trial. Scand J Rheumatol. 2019 Jul;48(4):340-341. doi: 10.1080/03009742.2018.1559880. Epub 2019 May 27. No abstract available.

  PMID: 31132016 RESULT

• Boers M, Hartman L, Opris-Belinski D, Bos R, Kok MR, Da Silva JA, Griep EN, Klaasen R, Allaart CF, Baudoin P, Raterman HG, Szekanecz Z, Buttgereit F, Masaryk P, Klausch LT, Paolino S, Schilder AM, Lems WF, Cutolo M; GLORIA Trial consortium. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis. 2022 Jul;81(7):925-936. doi: 10.1136/annrheumdis-2021-221957. Epub 2022 May 31.

  PMID: 35641125 RESULT

• Hartman L, da Silva JAP, Buttgereit F, Cutolo M, Opris-Belinski D, Szekanecz Z, Masaryk P, Voshaar MJH, Heymans MW, Lems WF, van der Heijde DMFM, Boers M. Development of prediction models to select older RA patients with comorbidities for treatment with chronic low-dose glucocorticoids. Rheumatology (Oxford). 2023 May 2;62(5):1824-1833. doi: 10.1093/rheumatology/keac547.

  PMID: 36165675 RESULT

• Hartman L, El Alili M, Cutolo M, Opris D, Da Silva J, Szekanecz Z, Buttgereit F, Masaryk P, Bos R, Kok MR, Paolino S, Coupe V, Lems WF, Boers M; GLORIA consortium. Cost-effectiveness and cost-utility of add-on, low-dose prednisolone in patients with rheumatoid arthritis aged 65+: The pragmatic, multicenter, placebo-controlled GLORIA trial. Semin Arthritis Rheum. 2022 Dec;57:152109. doi: 10.1016/j.semarthrit.2022.152109. Epub 2022 Oct 21.

  PMID: 36335684 RESULT

• Palmowski A, Nielsen SM, Boyadzhieva Z, Schneider A, Pankow A, Hartman L, Da Silva JAP, Kirwan J, Wassenberg S, Dejaco C, Christensen R, Boers M, Buttgereit F. Safety and efficacy associated with long-term low-dose glucocorticoids in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford). 2023 Aug 1;62(8):2652-2660. doi: 10.1093/rheumatology/kead088.

  PMID: 36810945 DERIVED

Related Links

• description of DAS28 score instrument

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Prednisolone; Glucocorticoids

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; 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

Limitations and Caveats

Initially slow recruitment, initiatives to enhance recruitment and retention hampered or prohibited by strict and varying ethical guidelines across countries. The covid-19 pandemic compromised collection of important endpoint data. The pragmatic design caused confounding by treatment changes, most likely reducing the difference in benefit between the groups. Post-hoc specification of adverse event frequencies done outside of statistical analysis plan. See reference list (trial results).

Results Point of Contact

• Title: Prof Maarten Boers
• Organization: Amsterdam UMC, Vrije Universiteit

eb@amsterdamumc.nl

+3120-4444474

Study Officials

• Maarten Boers, Prof. dr.

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 20, 2015
• First Posted: October 23, 2015
• Study Start: June 30, 2016
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: expected active from 2022
• Access Criteria: scientific use

Locations

PT (5); IT (1); DE (3); HU (1); NL (15); RO (2); SL (1)