Administrative information
Title {1} | The efficacy of Methotrexate for glucocorticoid dose reduction in recently diagnosed polymyalgia rheumatica patients: a double-blind randomized placebo controlled multicenter clinical trial. |
Trial registration {2a and 2b}. | Dutch trial registration, NL8366 Registered on 2020-02-10 (CMO Regio Arnhem-Nijmegen NL69979.091.19, date 2020-01-23). |
Protocol version {1} | 20-07-2021 version 2.1 |
Funding {4} | This is an investigator driven trial and (partially) funded by ReumaNederland (funding number 18-2-401) |
Author details {5a} | Department of Rheumatology, Sint Maartenskliniek, Hengstdal 3, 6574 NA Nijmegen, The Netherlands Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands. Department of Rheumatic Diseases, Radboud Institute of Health Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands |
Name and contact information for the trial sponsor {5b} | Dr. Aatke van der Maas. Sint Maartenskliniek, Department of Rheumatology. PO box 9011, 6500 GM Nijmegen, The Netherlands A.vandermaas@maartenskliniek.nl fax number +31 24 3659743 telephone number. +31 24 3659985 |
Role of sponsor {5c} | The study funder had no role in the study design, collection, management and analysis. The study funder will not have a role in the interpretation of data; writing of the report; and the decision to submit the report for publication, nor will they ultimate have authority over any of these activities. |
Introduction
Background and rationale {6a}
Objectives {7}
Trial design {8}
Methods: participants, interventions, and outcomes
Study setting {9}
Eligibility criteria {10}
Inclusion criteria
Exclusion criteria
Who will take informed consent? {26a}
Additional consent provisions for collection and use of data {26b}
Interventions
Explanation for the choice of comparators {6b}
Intervention description {11a}
Time in weeks | 0 | 4 | 8 | 12 | 16 | 20 | 24 | 28 | 32 | 36 | 40 | 44 | 48 | 52 | |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
MTX group | Prednisolone (mg/day) | 15 | 12.5 | 10 | 7.5 | 5 | 2.5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
MTX (mg/week) | 15 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | 25 | |
Folic acid (mg/week) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | |
Placebo group | Prednisolone (mg/day) | 15 | 12.5 | 10 | 7.5 | 5 | 2.5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
MTX (mg/week) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |
Folic acid (mg/week) | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 | 10 |
Criteria for discontinuing or modifying allocated interventions {11b}
Strategies to improve adherence to interventions {11c}
Relevant concomitant care permitted or prohibited during the trial {11d}
Provisions for post-trial care {30}
Outcomes {12}
Participant timeline {13}
Sample size {14}
Proportion of GC-free remission | Placebo group | |||||||
---|---|---|---|---|---|---|---|---|
0.5 | 0.45 | 0.4 | 0.35 | 0.3 | 0.25 | 0.2 | ||
MTX group | 0.8 | 90 | 70 | 56 | 44 | 38 | 32 | 26 |
0.75 | 132 | 96 | 72 | 56 | 46 | 38 | 32 | |
0.7 | 206 | 136 | 98 | 74 | 58 | 46 | 38 | |
0.65 | 366 | 212 | 140 | 98 | 74 | 56 | 44 | |
0.6 | 816 | 372 | 214 | 140 | 98 | 72 | 56 | |
0.55 | 3210 | 824 | 372 | 212 | 136 | 96 | 70 | |
0.5 | 3210 | 816 | 366 | 206 | 132 | 90 |
Recruitment {15}
Methods: assignment of interventions: allocation
Sequence generation {16a}
Concealment mechanism {16b}
Implementation {16c}
Methods: assignment of interventions: blinding
Who will be blinded {17a}
Procedure for unblinding if needed {17b}
Methods: data collection and management
Plans for assessment and collection of outcomes {18a}
Timepoint | Enrolment | Post-allocation (weeks) | Close-out | |||||||
---|---|---|---|---|---|---|---|---|---|---|
-t1 | Baseline | 4 | 8 | 12 | 16 | 24 | 32 | 42 | 52 | |
Enrolment | ||||||||||
Eligibility screen | X | |||||||||
Informed consent | X | |||||||||
Allocation | X | |||||||||
Intervention | ||||||||||
Methotrexate | ||||||||||
Placebo | ||||||||||
Assessments | ||||||||||
Demographics, medical history, medication overview, RF, ACPA, AP | X | |||||||||
Disease characteristics, physical examination, PMR-AS, AE monitoring, PROsa | X | X | X | X | X | X | ||||
CRP, ESR, total blood count, creatinine, ALAT, serum for storage | X | X | X | X | X | X | X | X | X | |
GTI, including serum glucose, HbA1c, LDL | X | X | X | X |