IMPORTANCE trial: a provisional study-design of a single-center, phase II, double-blinded, placebo-controlled, randomized, 4-week study to compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain

F1000Res. 2021 Jan 22;10:42. doi: 10.12688/f1000research.27809.1. eCollection 2021.

Abstract

Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients' functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020.

Keywords: Cancer pain; Esketamine; Opioid refractory; Pain measurement.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Chronic Pain* / drug therapy
  • Double-Blind Method
  • Humans
  • Ketamine* / therapeutic use
  • Pain, Intractable*
  • Quality of Life
  • Treatment Outcome

Substances

  • Analgesics, Opioid
  • Esketamine
  • Ketamine

Associated data

  • figshare/10.6084/m9.figshare.13435742.v2
  • ClinicalTrials.gov/NCT04666623

Grant support

The author(s) declared that no grants were involved in supporting this work.