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Trials
Published in: Trials 1/2015

Open Access 01-12-2015 | Study protocol

Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial

Authors: Sarah R Kingsbury, Puvan Tharmanathan, Nigel K Arden, Michael Batley, Fraser Birrell, Kim Cocks, Michael Doherty, Chris J Edwards, Toby Garrood, Andrew J Grainger, Michael Green, Catherine Hewitt, Rod Hughes, Robert Moots, Terence W O’Neill, Edward Roddy, David L Scott, Fiona E Watt, David J Torgerson, Philip G Conaghan

Published in: Trials | Issue 1/2015

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Abstract

Background

Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain.

Methods/Design

Pain Reduction with Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre, randomized, double-blind, pragmatic placebo-controlled trial. A total of 160 participants with symptomatic knee OA will be recruited across primary and secondary care sites in the United Kingdom and randomized on a 1:1 basis to active treatment or placebo, in addition to usual care, for 12 months. As is usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or maximum tolerated dose) weekly for the remainder of the study. The primary endpoint is change in average knee pain during the past week (measured on an 11-point numerical rating scale) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures. A health economics analysis will also be performed. A magnetic resonance imaging substudy will be conducted to provide an explanatory mechanism for associated symptom change by examining whether MTX reduces synovitis and whether this is related to symptom change. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis.

Discussion

The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA.

Trial registration

Current Controlled Trials identifier: ISRCTN77854383 (registered: 25 October 2013).
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Metadata
Title
Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial
Authors
Sarah R Kingsbury
Puvan Tharmanathan
Nigel K Arden
Michael Batley
Fraser Birrell
Kim Cocks
Michael Doherty
Chris J Edwards
Toby Garrood
Andrew J Grainger
Michael Green
Catherine Hewitt
Rod Hughes
Robert Moots
Terence W O’Neill
Edward Roddy
David L Scott
Fiona E Watt
David J Torgerson
Philip G Conaghan
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Trials / Issue 1/2015
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-015-0602-8

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