Trial document




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  DRKS00004774

Trial Description

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Title

Comparison of the efficacy and safety of two starting dosages of prednisolone in early active rheumatoid arthritis: a randomized, placebo controlled trial

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Trial Acronym

CORRA

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URL of the Trial

http://www.ruhr-uni-bochum.de/corra

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Brief Summary in Lay Language

Although cortison 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.

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Brief Summary in Scientific Language

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).

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Organizational Data

  •   DRKS00004774
  •   2013/11/12
  •   2013/02/26
  •   yes
  •   Approved
  •   2013-250-f-A, Ethik-Kommission der Ärztekammer Westfalen-Lippe und der med. Fakultät der Westfälischen Wilhelms-Universität Münster
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Secondary IDs

  •   2012-004074-25 
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Health Condition or Problem studied

  •   M05 -  Seropositive rheumatoid arthritis
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Interventions/Observational Groups

  •   Prednihexal (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.
  •   Prednihexal (Prednisolon), daily oral atablet,
    10 mg during week one to four,
    7,5 mg during week five to eigth. Finally 5 mg for four weeks.
  •   Placebo
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Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Blinded
  •   patient/subject, investigator/therapist
  •   Placebo
  •   Treatment
  •   Parallel
  •   IV
  •   No
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Primary Outcome

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

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Secondary Outcome

1. Percentage of patients in remission as defined by DAS 28 < 2.6 (DAS 28 = Disease Activity Score 28) or in a state of low disease activity (DAS 28 ≥ 2.6 and DAS 28 < 3.2) after 12 weeks, 24 weeks and after one year (the DAS 28 score is a compound score comprising the number of tender joints (out of 28), swollen joints (out of 28), the ESR in mm (after 1 hour), and patient´s assessment of disease activity. The range of the score is between 0 (no activity) and 10 (maximum of disease activity), a range between 3.2 and 5.1 is regarded as reflecting a moderate disease activity,
2. changes of functional capacity (FfbH) at week 12 and after one year compared to baseline,
3. difference in bone mineral density (DXA lumbar spine and hip) at month 6 in comparison to baseline,
4. number of GC injections and overall dose of Triamcinolons over one year ,
5. direct costs of treatment/month over 1 year,
6. mean methotrexate dosage over one year,
7. patient global assessment of disease activity,
8. percentage of patients with switch to biological treatment in case of inefficacy of conventional DMARD therapy,
9. Progression of radiographic damage after one year as quantified by the Ratingen score. Determined at basline and after one year,
10. rate and SAE determined by structured questioning and laboratory test.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

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Recruitment

  •   Actual
  •   2014/02/10
  •   450
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

• Diagnosis of RA according to the ACR/EULAR 2010 criteria (Aletaha et al. 2010),
• disease duration < 3 years,
• active disease: DAS 28 ESR > 4 plus ≥ 3 swollen joints.
• adequate compliance related to medication and paticipating in examinations in assessment of the physician
• legal capacity
• sufficient German language skills to fill in the questioning forms
• written informed consent

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Exclusion Criteria

- age < 18 years
- pregnancy or planned pregnancy,
- presence or history of severe infections,
- systemic corticoid-therapy 2 weeks before study start,
- Prior treatment with DMARDs (except for hydroxychloroquin or sulfasalazine or methotrexate during the last four weeks before screening,
-intolarance or known of inefficacy of Methotrexat (MTX),
- 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,
- uncontrolled increased intraocular pressure,

- non-compliance,

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Addresses

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    • Ruhr-Universität Bochum
    • Universitätsstr. 150
    • 44780  Bochum
    • Germany
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    • Rheumazentrum Ruhrgebiet, Fachklinik für rheumatische Erkrankungen, Studienambulanz
    • Claudiusstr. 45
    • 44649  Herne
    • Germany
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    • Abteilung für medizinische Informatik, Biometrie und Epidemiologie
    • Mr.  Dr.  Dietmar  Krause 
    • Universitätsstr. 150
    • 44780  Bochum
    • Germany
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    • Abteilung für medizinische Informatik, Biometrie und Epidemiologie
    • Mr.  Dr.  Dietmar  Krause 
    • Universitätsstr. 150
    • 44780  Bochum
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting complete, follow-up complete
  •   2018/06/30
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Trial Publications, Results and other Documents

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