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

Progression of Rheumatoid Arthritis Clinical Trial

— CORRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02000336
• Other study ID #: 01KG1204
• Secondary ID: 2012-004074-25
• Status: Completed
• Phase: Phase 3
• Start date: January 2014
• Est. completion date: September 2019

Study information

• Verified date: April 2020
• Source: Ruhr University of Bochum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 395
• Est. completion date: September 2019
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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,

• 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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Progression of Rheumatoid Arthritis

Intervention

Drug:
• Prednisolone
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).
• Placebo

Locations

Country	Name	City	State
Germany	Rheumatologische Schwerpunktpraxis Bielefeld	Bielefeld
Germany	Rheumatologische Schwerpunktpraxis Bocholt	Bocholt
Germany	Rheumaticon Internistische Schwerpunktpraxis Immunologie, Rheumatologie, Osteologie JosefCarrée Bochum	Bochum
Germany	Rheumatologische Schwerpunktpraxis Bochum	Bochum
Germany	MVZ Dr. Kretzmann und Kollegen	Dortmund
Germany	Rheumapraxis Dortmund	Dortmund
Germany	Rheumatologische Schwerpunktpraxis Dortmund	Dortmund
Germany	Rheumapraxis Duisburg	Duisburg
Germany	Rheumapraxis Gelsenkirchen	Gelsenkirchen
Germany	Internistische und rheumatologische Praxis Gladbeck	Gladbeck
Germany	Facharztzentrum Hagen	Hagen
Germany	Orthopädisch-rheumatologische Schwerpunktpraxis	Hattingen
Germany	Rheumapraxis Hattingen	Hattingen
Germany	Rheumapraxis Herne	Herne
Germany	Rheumazentrum Ruhrgebiet	Herne
Germany	Rheumatologische Schwerpunktpraxis Lingen	Lingen
Germany	Rheumapraxis am EVK	Lippstadt
Germany	Rheumatologische Schwerpunktpraxis Marl	Marl
Germany	Rheumatologische Schwerpunktpraxis Minden	Minden
Germany	Rheumatologische Schwerpunktpraxis Münster	Münster
Germany	Rheumapraxis Oberhausen	Oberhausen
Germany	Rheumapraxis Paderborn	Paderborn
Germany	Rheumazentrum Ratingen	Ratingen
Germany	Rheumatologische Schwerpunktpraxis Rheine	Rheine
Germany	Rheumapraxis Warendorf	Warendorf

Sponsors (2)

Lead Sponsor	Collaborator
Prof. Dr. rer. nat. H.J. Trampisch	Ruhr University of Bochum

Country where clinical trial is conducted

Germany, 

References & Publications (25)

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* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	52 weeks
Secondary	Percentage of patients in remission	as defined by the DAS 28 score	12 weeks, 24 weeks, 52 weeks
Secondary	Changes of functional capacity	as defined by the so called "Hannover function questionnaire"	Baseline, 12 weeks, 52 weeks
Secondary	Patient's assessment of disease activity	on a scale between 0 and 10	Baseline, 4 weeks, 8 weeks, 12 weeks, 24 weeks, 52 weeks