Clinical trial NCT01986998: Study to Compare the Clinical and Radiological Efficacy of 625 mg Versus 1250 mg of Oral Methylprednisolone in Patients With Multiple Sclerosis in Relapse
Official title: Multicenter, Randomized, Double-blind Clinical Trial to Compare the Clinical and Radiological Efficacy of 625 mg Versus 1250 mg of Oral Methylprednisolone in Patients With Multiple Sclerosis in Relapse.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Multiple sclerosis relapse
oral methylprednisolone
EDSS
gadolinium
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
First posted: 2013-11-19
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Disability scale of Kurtzke EDSS score
timeFrame: up to day 91
Secondary outcomes:
measure: Adverse events / tolerability
timeFrame: Baseline and day 29
measure: Disability scale of Kurtzke EDSS score
timeFrame: Baseline and day 8
measure: The number and volume of active lesions (measured by the T2 or gadolinium enhancement), the number of new active lesions and the percentage of active lesions at baseline that becomes black holes
timeFrame: day -1 and day 29
measure: Adverse events / tolerability
timeFrame: Baseline and day 8
measure: Questionnaire MSQOL-54
timeFrame: Baseline and day 8
measure: Questionnaire MSQOL-54
timeFrame: Baseline and day 29
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias I Pujol de
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital de Mataró
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de Sant Joan Despí Moisés Broggi
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr. Josep Trueta
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Tarragona
country: Spain
facility: Hospital de Sant Pau I Santa Tecla
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Cristina Ramo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.