AzTrials
AzTrials

Progression of Rheumatoid ArthritisPhase 3CORRANCT02000336

Comparison of the Effectiveness of Two Different Dosages of Cortisone Compared to Placebo in Rheumatoid Arthritis

A Phase 3 study testing Prednisolone in people with Progression of Rheumatoid Arthritis, run by Prof. Dr. rer. nat. H.J. Trampisch at 25 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Although cortisone is widely used in the treatment of patients with early rheumatoid arthritis, the best dosage is not known. Therefore we will compare two standard prednisolon starting dosages and placebo in the treatment of patients with early active rheumatoid arthritis on the background of the established therapy… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Progression of Rheumatoid Arthritis
What is being tested?
Prednisolone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
395 participants
Where
25 sitesGermany
Study dates
Jan 2014to Sep 2019
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of rheumatoid arthritis based on expert opinion according to the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2009 criteria (Hawker 2009)
  • disease duration < 3 years
  • active disease: disease activity score (DAS) 28 erythrocyte sedimentation rate (ESR) (Prevoo et al 1995) > 4 plus ≥ 3 swollen joints

Who cannot join

  • Prior treatment with disease-modifying antirheumatic drugs (DMARDs) (except for hydroxychloroquine or sulfasalazine or methotrexate during the last four weeks before screening)
  • Clinically relevant comorbidity:
  • concurrent liver disease (ALT > 2 times upper limit of normal),
  • active hepatitis B or C viral infection,
  • renal disease (creatinine clearance < 30 ml/minute),
  • clinically relevant haematological disease due to the judgement of the rheumatologist,
Show all 17Show fewer
  • uncontrolled diabetes mellitus,
  • uncontrolled arterial hypertension,
  • relevant immunodeficiency incl. HIV-infection,
  • clinically significant pulmonary fibrosis,
  • history of malignant melanoma,
  • complicated or refractory gastrointestinal ulcers,
  • presence or history of severe infections,
  • uncontrolled increased intraocular pressure,
  • pregnancy or planned pregnancy,
  • non-compliance,
  • age < 18 years

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

Germany25 sites

  • Rheumatologische Schwerpunktpraxis Bielefeld

    Bielefeld, 33617

  • Rheumatologische Schwerpunktpraxis Bocholt

    Bocholt, 46397

  • Rheumatologische Schwerpunktpraxis Bochum

    Bochum, 44787

  • Rheumaticon Internistische Schwerpunktpraxis Immunologie, Rheumatologie, Osteologie JosefCarrée Bochum

    Bochum, 44791

  • Rheumapraxis Dortmund

    Dortmund, 44137

  • MVZ Dr. Kretzmann und Kollegen

    Dortmund, 44147

  • Rheumatologische Schwerpunktpraxis Dortmund

    Dortmund, 44263

  • Rheumapraxis Duisburg

    Duisburg, 47057

  • Rheumapraxis Gelsenkirchen

    Gelsenkirchen, 45891

  • Internistische und rheumatologische Praxis Gladbeck

    Gladbeck, 45964

  • Facharztzentrum Hagen

    Hagen, 58089

  • Orthopädisch-rheumatologische Schwerpunktpraxis

    Hattingen, 45525

  • Rheumapraxis Hattingen

    Hattingen, 45525

  • Rheumazentrum Ruhrgebiet

    Herne, 44649

  • Rheumapraxis Herne

    Herne, 44652

  • Rheumatologische Schwerpunktpraxis Lingen

    Lingen, 49808

  • Rheumapraxis am EVK

    Lippstadt, 59555

  • Rheumatologische Schwerpunktpraxis Marl

    Marl, 45768

  • Rheumatologische Schwerpunktpraxis Minden

    Minden, 32425

  • Rheumatologische Schwerpunktpraxis Münster

    Münster, 48143

  • Rheumapraxis Oberhausen

    Oberhausen, 46145

  • Rheumapraxis Paderborn

    Paderborn, 33098

  • Rheumazentrum Ratingen

    Ratingen, 40878

  • Rheumatologische Schwerpunktpraxis Rheine

    Rheine, 48431

  • Rheumapraxis Warendorf

    Warendorf, 48231

Other trials in Germany

About this study

Official title: Comparison of the Efficacy and Safety of Two Different Starting Dosages of Prednisolone in Early Active Rheumatoid Arthritis: a Randomized, Placebo Controlled Trial

Although cortisone is widely used in the treatment of patients with early rheumatoid arthritis, the best dosage is not known. Therefore we will compare two standard prednisolon starting dosages and placebo in the treatment of patients with early active rheumatoid arthritis on the background of the established therapy with methotrexate. In total 450 patients will be included into the study. Two different treatment arms starting with 10 or 60 mg of prednisolone, and one placebo arm. Duration of intervention is 12 weeks. In parallel, all patients start medication with methotrexate, usual dosage 15 mg/week. Primary efficacy endpoint is progression of radiographic damage after one year compared to baseline. Safety monitoring is performed.

Read the detailed description

BACKGROUND: Although glucocorticoids (GCs) are widely used in the treatment of patients with early rheumatoid arthritis (RA), the best dosage for GCs, related to both, efficacy and safety, is not known.

OBJECTIVE: To compare two standard p.o. GC starting dosages and the non-use of GCs in the treatment of patients with early active RA on the background of the established 'anchor' therapy with methotrexate (MTX).

METHODS: Randomised double-blind placebo-controlled trial with two treatment arms (starting with 10 or 60 mg of p.o. prednisolone (P), tapered down to 5 mg P per day within 8 weeks) and one placebo arm, each arm comprising 150 patients. Duration of intervention is 12 weeks. In parallel, all patients start medication with MTX, usual dosage 15 mg/week. Primary efficacy endpoint is progression of radiographic damage after one year compared to baseline. Secondary endpoints are: percentage of patients in remission, changes of functional capacity etc. Safety monitoring is performed.

The analysis is performed in three hierarchical steps. First step is an analysis of covariance to compare the group with an initial P dosage of 60 mg (V60) and the placebo group (Pl). In case of a statistical significant result (α = 0.05), a comparison of the group starting with 10 mg P (V10) and Pl will be done in a second step (α = 0.05). In case of superiority of V10 versus Pl, a third step will be a non-inferiority test for V10 versus V60 (α = 0.025).

Being tested
Prednisolone, Placebo
Keywords
radiographic damage, rheumatoid arthritis
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PrednisoloneDrug

    Also called PredniHexal

    To compare two standard p.o. GC starting dosages and the non-use of GCs in the treatment of patients with early active RA on the background of the established 'anchor' therapy with methotrexate (MTX).

  • PlaceboDrug

Study groups in NCT02000336
Study groupRoleWhat they receive
Prednisolone 10ExperimentalPrednihexal (Prednisolon), daily oral tablet, 10 mg during week one to four, 7,5 mg during week five to eight. Finally 5 mg for four weeks.
Receives: Drug: Prednisolone
Prednisolone 60ExperimentalPrednihexal (Prednisolon), daily oral tablet, 60 mg during the first week, weekly tapering: 40 mg, 20mg, 15mg, 10mg, 7,5mg. 7,5mg continued for one more week. Finally 5 mg for four weeks
Receives: Drug: Prednisolone
PlaceboPlacebo comparatordaily oral tablet
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression of radiographic damage after one year as quantified by the van der Heijde modification of the Sharp score (SHS). Determined at baseline and after one year.

    15 sites in each hand and wrist and six joints in each foot are examined for joint space narrowing on a scale of 0 to 437: 0 indicates no narrowing, 1 represents minimal narrowing, 2 indicates loss of 50% of the joint space, 3 indicates loss of 75% of the joint space, and 4 represents complete loss of the joint space. The erosions are counted individually, usually at 16 sites in each hand and wrist and six sites in each foot, with a maximum score of 5 given for a destroyed hand or foot joint. For joints in the feet, the van der Heijde version of the Sharp scoring system has a maximum score of 10 for a destroyed joint

    Measured: 52 weeks

Secondary outcomes (3)

  1. Percentage of patients in remission

    as defined by the DAS 28 score

    Measured: 12 weeks, 24 weeks, 52 weeks

  2. Changes of functional capacity

    as defined by the so called "Hannover function questionnaire"

    Measured: Baseline, 12 weeks, 52 weeks

  3. Patient's assessment of disease activity

    on a scale between 0 and 10

    Measured: Baseline, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Dec 2013 (estimated)
  2. Study startJan 2014
  3. Primary completionMar 2018
  4. Study completionSep 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
395 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02000336
Sponsor's protocol ID
01KG1204
Other IDs
2012-004074-25
Acronym
CORRA
Status last verified
Apr 2020
First submitted
19 Nov 2013
Last updated
10 Apr 2020
Results posted
No
Data monitoring committee
Yes

Publications

  • Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Menard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81. doi: 10.1002/art.27584.

    PubMed 20872595

  • Bakker MF, Jacobs JW, Welsing PM, Verstappen SM, Tekstra J, Ton E, Geurts MA, van der Werf JH, van Albada-Kuipers GA, Jahangier-de Veen ZN, van der Veen MJ, Verhoef CM, Lafeber FP, Bijlsma JW; Utrecht Rheumatoid Arthritis Cohort Study Group. Low-dose prednisone inclusion in a methotrexate-based, tight control strategy for early rheumatoid arthritis: a randomized trial. Ann Intern Med. 2012 Mar 6;156(5):329-39. doi: 10.7326/0003-4819-156-5-201203060-00004.

    PubMed 22393128

  • Bijlsma JW, van der Goes MC, Hoes JN, Jacobs JW, Buttgereit F, Kirwan J. Low-dose glucocorticoid therapy in rheumatoid arthritis: an obligatory therapy. Ann N Y Acad Sci. 2010 Apr;1193:123-6. doi: 10.1111/j.1749-6632.2009.05342.x.

    PubMed 20398017

  • Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309-18. doi: 10.1016/S0140-6736(97)01300-7.

    PubMed 9251634

  • Breedveld FC, Han C, Bala M, van der Heijde D, Baker D, Kavanaugh AF, Maini RN, Lipsky PE. Association between baseline radiographic damage and improvement in physical function after treatment of patients with rheumatoid arthritis. Ann Rheum Dis. 2005 Jan;64(1):52-5. doi: 10.1136/ard.2003.017160. Epub 2004 Jul 29.

    PubMed 15286005

  • Capell HA, Madhok R, Hunter JA, Porter D, Morrison E, Larkin J, Thomson EA, Hampson R, Poon FW. Lack of radiological and clinical benefit over two years of low dose prednisolone for rheumatoid arthritis: results of a randomised controlled trial. Ann Rheum Dis. 2004 Jul;63(7):797-803. doi: 10.1136/ard.2003.014050.

    PubMed 15194574

  • Choy EH, Smith CM, Farewell V, Walker D, Hassell A, Chau L, Scott DL; CARDERA (Combination Anti-Rheumatic Drugs in Early Rheumatoid Arhritis) Trial Group. Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis. 2008 May;67(5):656-63. doi: 10.1136/ard.2007.076299. Epub 2007 Sep 3.

    PubMed 17768173

  • Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005 Nov;52(11):3381-90. doi: 10.1002/art.21405.

    PubMed 16258899

  • Grigor C, Capell H, Stirling A, McMahon AD, Lock P, Vallance R, Kincaid W, Porter D. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004 Jul 17-23;364(9430):263-9. doi: 10.1016/S0140-6736(04)16676-2.

    PubMed 15262104

  • Gorter SL, Bijlsma JW, Cutolo M, Gomez-Reino J, Kouloumas M, Smolen JS, Landewe R. Current evidence for the management of rheumatoid arthritis with glucocorticoids: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010 Jun;69(6):1010-4. doi: 10.1136/ard.2009.127332. Epub 2010 May 6.

    PubMed 20448288

  • Hoes JN, Jacobs JW, Verstappen SM, Bijlsma JW, Van der Heijden GJ. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann Rheum Dis. 2009 Dec;68(12):1833-8. doi: 10.1136/ard.2008.100008. Epub 2008 Dec 9.

    PubMed 19066177

  • Hoes JN, Jacobs JW, Buttgereit F, Bijlsma JW. Current view of glucocorticoid co-therapy with DMARDs in rheumatoid arthritis. Nat Rev Rheumatol. 2010 Dec;6(12):693-702. doi: 10.1038/nrrheum.2010.179.

    PubMed 21119718

  • Kirwan JR. The effect of glucocorticoids on joint destruction in rheumatoid arthritis. The Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group. N Engl J Med. 1995 Jul 20;333(3):142-6. doi: 10.1056/NEJM199507203330302.

    PubMed 7791815

  • Mottonen T, Hannonen P, Leirisalo-Repo M, Nissila M, Kautiainen H, Korpela M, Laasonen L, Julkunen H, Luukkainen R, Vuori K, Paimela L, Blafield H, Hakala M, Ilva K, Yli-Kerttula U, Puolakka K, Jarvinen P, Hakola M, Piirainen H, Ahonen J, Palvimaki I, Forsberg S, Koota K, Friman C. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet. 1999 May 8;353(9164):1568-73. doi: 10.1016/s0140-6736(98)08513-4.

    PubMed 10334255

  • Mouterde G, Dernis E, Ruyssen-Witrand A, Claudepierre P, Schaeverbeke T, Cantagrel A, Gaudin P, Maillefert JF, Pham T, Saraux A, Tebib J, Wendling D, Fautrel B, Le Loet X. Indications of glucocorticoids in early arthritis and rheumatoid arthritis: recommendations for clinical practice based on data from the literature and expert opinion. Joint Bone Spine. 2010 Dec;77(6):597-603. doi: 10.1016/j.jbspin.2009.12.011. Epub 2010 Jul 1.

    PubMed 20594896

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Prednisolone in people with Progression of Rheumatoid Arthritis, run by Prof. Dr. rer. nat. H.J. Trampisch at 25 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression of radiographic damage after one year as quantified by the van der Heijde modification of the Sharp score (SHS). Determined at baseline and after one year. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02000336, which also lists 26 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Apr 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in