Discontinuing a non-steroidal anti-inflammatory drug (NSAID) in patients with knee osteoarthritis: Design and protocol of a placebo-controlled, noninferiority, randomized withdrawal trial

Contemp Clin Trials. 2018 Feb:65:1-7. doi: 10.1016/j.cct.2017.11.020. Epub 2017 Dec 2.

Abstract

Background: Knee osteoarthritis (OA) is the most common cause of knee pain in older adults. Despite the limited data supporting their use, non-steroidal anti-inflammatory drugs (NSAID) are among the most commonly prescribed medications for knee OA. The use of NSAIDs for knee pain warrants careful examination because of toxicity associated with this class of medications.

Methods: We describe the design of a placebo-controlled, noninferiority, randomized withdrawal trial to examine discontinuation of an NSAID in patients with painful knee OA. Participants will be veterans enrolled in the VA Healthcare System with knee OA pain despite NSAID use and/or relatively higher risk of NSAID toxicity. After a two-week run-in period where eligible subjects will replace their current NSAID with the study NSAID (meloxicam), those remaining eligible (target N=544) will be randomized to receive four weeks of either placebo or continued meloxicam. The primary outcome is knee pain (Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, range 0-20) at four weeks post-randomization. The primary hypothesis is that placebo will be noninferior to (that is, not much worse than) meloxicam within a noninferiority margin of 1. Secondary outcomes include lower extremity disability, global impression of change, adherence to study medication and use of co-therapies.

Discussion: This study is the first clinical trial to date examining the effects of withdrawing an NSAID for OA knee pain. If successful, this trial will provide evidence against the continued use of NSAIDs in patients with OA knee pain.

Trial registration: ClinicalTrials.gov: NCT01799213. Registered February 22, 2013.

Keywords: Knee osteoarthritis; NSAID; Noninferiority trial; Randomized clinical trial; Withdrawal trial.

Publication types

  • Clinical Trial Protocol
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetaminophen / therapeutic use
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Disability Evaluation
  • Double-Blind Method
  • Equivalence Trials as Topic
  • Female
  • Humans
  • Male
  • Meloxicam / administration & dosage
  • Meloxicam / adverse effects
  • Meloxicam / therapeutic use*
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Pain Measurement
  • Patient Education as Topic / methods
  • Randomized Controlled Trials as Topic
  • Research Design
  • Severity of Illness Index
  • Sex Factors
  • Social Support
  • Young Adult

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen
  • Meloxicam

Associated data

  • ClinicalTrials.gov/NCT01799213