Study to Compare the Clinical and Radiological Efficacy of 625 mg Versus 1250 mg of Oral Methylprednisolone in Patients With Multiple Sclerosis in Relapse

NCT ID: NCT01986998

Last Updated: 2016-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2016-03-31

Brief Summary

The investigators plan to carry out a multicenter randomized clinical trial and MRI study of high-dose oMP (1250mg/day for 3 days) versus lower-high dose oMP (625mg/day for 3 days) and demonstrated that lower-high dose of oMP is as effective as a higher-high dose of oMP in acute relapse of multiple sclerosis (MS). If it is shown, our purpose is to promote this therapeutic regimen because it is safer for the patient (less adverse effects) and less costly to the healthcare system.

Detailed Description

DESIGN: Phase IV clinical trial, multicentre, randomized and double blind, active drug controlled and parallel groups. Patients will be randomised to a high dose of oMP vs a lower-high dose of oral Methylprednisolone (oMP).

SETTING: 9 MS Units from 9 hospitals of the public health system with extensive experience in treating patients with MS and design and participation in clinical trials.

PROCEDURES:

After signing the informed consent, the inclusion and exclusion criteria specific to the study will be checked. The diagnostic test will take place prior to administration of study medication and will include medical history, neurological examination (EDSS measurement) taking of vital signs (blood pressure, heart rate and body temperature) and MRI. Concomitant medication will be checked. Patients will be instructed about the requirements during the study.

The trial medication will be provided to the patient in the medical office (day 1 of the study), where the patient will remain until the intake. This action will be repeated the following 2 days. The latency period from the beginning of the relapse until the start of treatment will be registered. The questionnaires of tolerance will be completed.

Day 1 will be defined as the first day on which first dose of oMP is administered.

Once given the treatment under study, the adverse events reported spontaneously or after question will be collected.

There will be follow-up visits at 7 and 28 days, and 3 months after initiation of treatment. At baseline, prior to drug administration, and on days 7 and 28 after initiation of treatment, a brain MRI with and without contrast will be performed. In case of adverse events or laboratory abnormalities, the patients could have an accessory follow-up visits until resolution.

Randomization will be performed on the day of administration (day 1)

The treatments are:

Group A: Methylprednisolone 1250 mg / day orally for 3 days Group B: Methylprednisolone 625 mg / day orally for 3 days

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

oMP 1250 mg: Group A

Methylprednisolone 1250 mg/24h x3 days

Group Type: ACTIVE_COMPARATOR

Methylprednisolone 1250 mg/24h x3 days

Intervention Type: DRUG

Oral Methylprednisolone 1.250 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (12 capsules of 100 mg and 1 capsule of 50 mg)

oMP 625 mg: Group B

Methylprednisolone oral 625 mg/24h x3 days

Group Type: ACTIVE_COMPARATOR

Oral Methylprednisolone 625 mg/24h x3 days

Intervention Type: DRUG

Oral Methylprednisolone 625 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (6 capsules of 100 mg, 1 capsule of 25 mg and 6 capsules of placebo with the same appearance of capsules of 100 mg)

Interventions

Methylprednisolone 1250 mg/24h x3 days

Oral Methylprednisolone 1.250 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (12 capsules of 100 mg and 1 capsule of 50 mg)

Intervention Type: DRUG

Oral Methylprednisolone 625 mg/24h x3 days

Oral Methylprednisolone 625 mg daily, over 1 hour and during 3 consecutive days. 13 capsules will be administered (6 capsules of 100 mg, 1 capsule of 25 mg and 6 capsules of placebo with the same appearance of capsules of 100 mg)

Intervention Type: DRUG

Other Intervention Names

Group A; Group B

Eligibility Criteria

Inclusion Criteria

1. Relapsing-remitting MS (Mc Donald criteria 2010) regardless being under immunomodulatory treatment

2. EDSS (previous to relapse) between 0 and 5

3. MS relapse of moderate intensity (EDSS increase from 1 to 2.5 points) or severe intensity (EDSS increase > 3 points)

• If EDSS previous relapse is available:

• optic neuritis, myelitis or brainstem relapse: the EDSS should increase of 1 point in visual, pyramidal or brainstem system function
• relapse in other location or uncertain location: the EDSS should increase at least 1 point
• If EDSS previous relapse is not available:

• optic neuritis, myelitis or brainstem relapse: the visual, pyramidal or brainstem system function should be > 2 points.
• relapse in other location or uncertain location: EDSS should be > 2 points

4. Recent clinical relapse onset (<15 days) without fever

5. One month of clinical stability prior to relapse

6. Signed informed consent

7. Capacity to ingest the medication.

Exclusion Criteria

1. Doubts about the diagnosis of multiple sclerosis

2. First episode of inflammatory neurological disease

3. Secondary progressive MS or primary progressive MS

4. Symptoms with lasted less than 24 hours of evolution

5. Any degree of subjective or objective remission

6. Treatment with corticosteroids during the previous 30 days

7. Patients with immunosuppressive treatment (azathioprine, mitoxantrone, cyclophosphamide) or Natalizumab or Fingolimod

8. Pregnancy or breastfeeding women or women of childbearing potential not using contraceptive measures

9. Diseases with a contraindication of treatment with corticosteroids

10. History of serious adverse reaction or hypersensitivity to drugs related to study medication

11. Patients who could not be regular MRI, not collaborators or who requires anesthesia.

12. Lactose intolerance

13. Patients with allergies to contrast used in MRI

14. Patients with renal impairment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Germans Trias i Pujol Hospital

OTHER

Sponsor Role: lead

Responsible Party

Cristina Ramo

Cristina Ramo

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cristina Ramo, MD

Role: PRINCIPAL_INVESTIGATOR

Germans Trias i Pujol Hospital

Locations

Hospital Universitari Germans Trias I Pujol de

Badalona, Barcelona, Spain

Hospital Del Mar

Barcelona, Barcelona, Spain

Hospital de Mataró

Barcelona, Barcelona, Spain

Hospital Clinic I Provincial de Barcelona

Barcelona, Barcelona, Spain

Hospital de Sant Joan Despí Moisés Broggi

Barcelona, Barcelona, Spain

Hospital Universitari de Girona Dr. Josep Trueta

Girona, Girona, Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, Lleida, Spain

Hospital de Sant Pau I Santa Tecla

Tarragona, Tarragona, Spain

Countries

Spain

References

Hervas-Garcia JV, Ramio-Torrenta L, Brieva-Ruiz L, Batlle-Nadal J, Moral E, Blanco Y, Cano-Orgaz A, Presas-Rodriguez S, Torres F, Capellades J, Ramo-Tello C. Comparison of two high doses of oral methylprednisolone for multiple sclerosis relapses: a pilot, multicentre, randomized, double-blind, non-inferiority trial. Eur J Neurol. 2019 Mar;26(3):525-532. doi: 10.1111/ene.13851. Epub 2018 Nov 16.

Reference Type: DERIVED

PMID: 30351511 (View on PubMed)

Other Identifiers

2012-001965-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

oral-CORTEM

Identifier Type: -

Identifier Source: org_study_id