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Table 4 Eligibility criteria

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

Inclusion criteria Exclusion criteria
Fulfil clinical ACR Criteria for knee OA The presence of any inflammatory arthritis (such as gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, seronegative spondyloarthropathy, previous diagnosis of pseudogout in target joint with proven crystals on joint aspiration or elevated CRP at time of knee arthritis flare) or fibromyalgia.
Knee pain on most days in the last 3 months
Knee pain is the predominant pain condition Use of intra-articular (IA) hyaluronic acid in the signal knee within the 4 months preceding enrolment in the studya
Insufficient pain relief from, inability to tolerate or contra-indication to oral and/or topical NSAIDs and/or opioids. Moderate to severe pain of the signal knee as defined by a score of ≥40 mm on a VAS (0 to 100 mm) using the question ‘On average, how would you rate your knee pain during the last 3 months?’. Use of IA, IM (intra-muscular) or oral corticosteroids in the 3 months preceding enrolmenta
Use of other anti-synovial agents (such as hydroxychloroquine or sulphasalazine) in the 2 months preceding the studya
Significant knee injury or any knee surgery within the 6 months preceding enrolment in the studya
Patient able to identify a ‘signal’ painful knee (either the most painful knee or selected from equally painful knees) The presence of non-OA causes of pain in the signal knee, such as referred hip pain, osteonecrosis or radicular spinal pain
A previous radiograph (X-ray) of the signal knee within the last 2 years with changes consistent with tibiofemoral OA Commencement of physiotherapy or non-pharmacological knee OA treatment in the 2 months preceding the studya
No change in the average weekly dose of oral or topical analgesics (including NSAIDs) for at least 4 weeksa A history of partial or complete joint replacement surgery in the signal knee at any time, listed for knee surgery or anticipating knee surgery during the study period
Has used chondroitin or glucosamine for at least 3 months with no change to the average weekly dose, is not using or is willing to stop using if recently starteda Women who are pregnant, breast-feeding or men or women planning pregnancy within 18 months after screening (approximately 6 months following last study medications)
All male and female subjects biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and 24 weeks after the end of the study period. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives. Use of any investigational (unlicensed) drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longera
Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease
If female have potential for child bearing then a negative pregnancy test must be performed prior to starting treatment. Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period
The patient must be able to adhere to the study visit schedule and other protocol requirements Uncontrolled disease states, such as moderate or severe asthma, COPD or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids, or recurrent infections
The patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures Unwilling to keep alcohol intake to below the recommended maximum daily limit during the trial (2 units per day for women, 3 units per day for men)
All patients must have had a chest radiograph (X-ray) within the last 6 months Planned need for live vaccination during 12 months of study (for example for foreign travel) with exception of Zostavax®, which is permissible
Aged ≥18 years Melanoma or non-skin cancer in the past 3 yearsa
Intolerance to lactose
Significant haematological or biochemical abnormality:
Haemoglobin ≤8.5 g/dL
WCC ≤3.5 × 109/L
Neutrophils ≤1.5 × 109/L
Platelets ≤100 × 109/L
ALT >2 times ULN for the laboratory conducting the test.
Creatinine >1.5 times ULN for the laboratory conducting the tested
eGFR <30 mL/minute
  1. aCriteria for which participants may be rescreened if they are ineligible at the initial screening visit. ALT, alanine aminotransferase; COPD, chronic obstructive pulmonary disease; eGFR, estimated glomerular filtration rate; IA, intra-articular; IM, intramuscular; IV, intravenous; RA, rheumatoid arthritis; ULN, upper limit of normal; VAS, visual analogue scale; WCC, white cell count.