Combined Treatment of Methotrexate + Glucocorticoids Versus Glucocorticoids Alone in Patients With Polymyositis and Dermatomyositis (Prometheus)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Karolinska Institutet
Information provided by (Responsible Party):
Institute of Rheumatology, Prague
ClinicalTrials.gov Identifier:
NCT00651040
First received: March 31, 2008
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

Therapeutical trial in patients with idiopathic polymyositis and dermatomyositis is proposed. The study will investigate the safety and efficacy of combined methotrexate + glucocorticoids treatment compared with glucocorticoids alone.

This will be a randomised, open-label, assessor-blind, international multicenter trial, performed in several European centres interested in research on inflammatory myopathies.

A total number of 50 patients with polymyositis/dermatomyositis will be randomised into two groups (1: Methotrexate + glucocorticoids and 2: Glucocorticoids only). Patients will be equally distributed between the two groups providing 25 patients per treatment arm. The randomisation will be based on random numbers generated by a computer program. After being enrolled in the study, the patients will receive 12 months of therapy followed by a 12-month follow-up period.

The primary endpoint is the total dose of glucocorticoids (calculated in mg/kg weight), which will be administered for 12 months between baseline and the end of treatment.

There are several of secondary objectives, which will be pursued during and after the trial. Disease activity and damage will be prospectively assessed by the newly developed tools for myositis disease activity (MYOACT and MITAX) and for myositis damage (MYODAM and MDI. Other secondary objectives comprise: global assessment of activity and damage by patients and by physician, muscle endurance, muscle strength by manual muscle testing, enzyme levels, glucocorticoid related side effects, functional ability measured by HAQ, quality of life by SF-36, and number of patients with treatment failures. The other aims will also include (i) search for reliable prognostic parameters in the further prognosis of patients with inflammatory myopathies and (ii) studies on the pathogenic aspects of inflammatory myopathies. The investigations of serum, lymphocytes, muscle tissue and MRI will be organized. DNA and RNA will be stored for future genetic studies.

Patients with definite or probable polymyositis or dermatomyositis diagnosed according to diagnostic criteria will be enrolled. They will have disease activity that according to physician's own judgement requires high dose immunosuppressive treatment (based on clinical assessment of weakness, elevation of muscle enzymes and, if available, on magnetic resonance imaging findings). Patients should be previously untreated with the exception of glucocorticoid treatment up to 8 weeks.

Patients with other than primary idiopathic polymyositis or dermatomyositis, such as drug-induced myositis, myositis in association with other connective tissue disease, inclusion body myositis, malignancy related myositis, and juvenile dermatomyositis will be excluded.

All patients will start with prednisone 1 mg/kg/day and the dose will be tapered if patients meet definition of improvement, which has been proposed by IMACS group. Methotrexate will be administered orally, once weekly, with a starting dose 10 mg. This will be increased gradually to 25 mg/week if tolerated by week 5. Patients will be first assessed after 2 weeks and than monthly for a period of 48 weeks. There will be a follow-up after a further 1 year in order to find out the impact of the early treatment on the long-term disease outcome.

All efficacy analyses will be performed using intention-to-treat population (ITT). In addition, the primary and secondary variables will be analysed using the per-protocol population, which will contain all patients in the ITT population, who also reached Week 48 of treatment without any major protocol violations. The safety population, which will contain any patient who received at least one dose of study drug, will be used for all safety analyses.


Condition Intervention Phase
Polymyositis
Dermatomyositis
Drug: Prednisone
Drug: Methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Treatment
Official Title: A Prospective, Randomised, Assessor-blind, Multicenter Study of Efficacy and Safety of Combined Treatment of Methotrexate + Glucocorticoids Versus Glucocorticoids Alone in Patients With Polymyositis and Dermatomyositis.

Resource links provided by NLM:


Further study details as provided by Institute of Rheumatology, Prague:

Primary Outcome Measures:
  • The primary endpoint that will be measured is the total dose of glucocorticoids administered between baseline and the end of treatment. [ Time Frame: 1 year and the 2. year follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assessment of disease activity and damage,muscle strength and endurance, enzyme levels, glucocorticoid side-effects, dose, HAQ,SF-36, treatment failures [ Time Frame: 1 year and the 2. year follow up ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: May 2008
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1

Prednisone will be administered orally, initially at 1.0 mg/kg/day dosage and then tapered gradually equally in the two arms.

ARM 1 has only Prednisone

Drug: Prednisone
Prednisone will be administered orally, initially at 1.0 mg/kg/day dosage and then tapered gradually equally in the two arms
Active Comparator: 2
MTX will be administered orally (in case of oral intolerance intramusculary (i.m.)), once weekly for 48 weeks. There will be a clinically oriented dose escalation starting from 10 up to 20-25 mg of MTX. Five to ten mg of folic acid will be given 24 hours after each methotrexate dose.
Drug: Methotrexate
MTX will be administered orally (in case of oral intolerance intramusculary (i.m.)), once weekly for 48 weeks. There will be a clinically oriented dose escalation starting from 10 up to 20-25 mg of MTX. Five to ten mg of folic acid will be given 24 hours after each methotrexate dose.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age between 18 - 80 years.
  2. Patients with definite or probable polymyositis or dermatomyositis diagnosed according to diagnostic criteria (9, 10) (Appendix 1)
  3. Physician's own judgment of the disease activity that requires high dose immunosuppressive treatment (based on clinical assessment of weakness, elevation of muscle enzymes and, if available, on magnetic resonance imaging findings).
  4. Previously untreated patients with the exception of glucocorticoid treatment up to 8 weeks
  5. Signed informed consent.

Exclusion Criteria:

  1. Treatment with any immunosuppressive drug prior the study start.
  2. Treatment with glucocorticoids (> 20 mg of Prednisone or equivalent) more than 8 weeks prior to study start.
  3. Drug induced myositis.
  4. Polymyositis and dermatomyositis in association with other connective tissue disease.
  5. Inclusion body myositis.
  6. Patients with immunodeficiency syndrome.
  7. Pregnancy and lactation.
  8. Fertile women not using adequate contraception during the study, women planning to have children during the study course or 12 months after the end of the study.
  9. Malignancy.
  10. Juvenile dermatomyositis.
  11. Uncontrolled, clinically significant hematological, cardiovascular, pulmonary, endocrine, metabolic, gastrointestinal, hepatic or renal disease, which according to physician's consideration would interfere with high dose glucocorticoid and immunosuppressive treatment or would prevent to follow the treatment protocol.
  12. Severe infection.
  13. History of drug or alcohol abuse within the previous 6 months.
  14. Patients known to be HIV positive.
  15. Known hypersensitivity to methotrexate.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00651040

Locations
Czech Republic
Revmatologicky ustav
Prague, Czech Republic, 12850
Sponsors and Collaborators
Institute of Rheumatology, Prague
Karolinska Institutet
Investigators
Principal Investigator: Jiri Vencovsky, prof. MD. Institute of Rheumatology, Prague
  More Information

No publications provided

Responsible Party: Institute of Rheumatology, Prague
ClinicalTrials.gov Identifier: NCT00651040     History of Changes
Other Study ID Numbers: 3401
Study First Received: March 31, 2008
Last Updated: October 21, 2013
Health Authority: Czech Republic: State Institute for Drug Control

Keywords provided by Institute of Rheumatology, Prague:
Polymyositis
Dermatomyositis
Glucocorticoids
Methotrexate

Additional relevant MeSH terms:
Dermatomyositis
Polymyositis
Myositis
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Connective Tissue Diseases
Skin Diseases
Glucocorticoids
Prednisone
Methotrexate
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 15, 2014