compare the efficacy and safety of intranasal esketamine in chronic opioid refractory pain

Conditions: Cancer Pain

Summary: this study is to assess the efficacy and safety of a four-week treatment with intranasal esketamine (56 mg) twice a week combined with opioid analgesic and adjuvant standard therapy in the management of adult patients with severe and opioid refractory chronic cancer pain.


Eligibility criteria:
inclusion criteria: * patient with refractory cancer pain, this pain defined when: * multiple evidence- based biomedical therapies used in a clinically appropriate and acceptable fashion have failed to reach treatment goals that mainly include adequate pain reduction and/or improvement in daily living functioning activities. * patients' functional activities do not allow a quality of life which is acceptable and/or pharmaceutical therapies have resulted in intolerable adverse effects. * psychiatric disorders and psychosocial factors that could influence pain outcomes have been assessed and appropriately addressed * cancer pain classified as chronic (persistent or recurrent pain lasting longer than 3 months), and currently refractory despite optimized analgesic therapy including an opioid. • optimized analgesic therapy is arbitrarily defined as: oral morphine equivalent of 60 mg/d or more (or another strong opioid at optimized dose) plus at least one adjuvant analgesic drug, for at least 2 weeks. * no increase in baseline long acting opioid dose or addition of a new adjuvant analgesic drug within 2 weeks prior to study entry * ability to communicate the intensity of pain using the nprs pain scale ranging from (0 as no pain to 10 with severe pain). * ability to give fully informed written consent. * expect survival more than 3 months. exclusion criteria: * history of allergy or intolerance to esketamine or ketamine. * history of allergy to disinfecting products containing quaternary ammonium, who might be susceptible to be allergic to denatonium benzoate. * concomitant use of xanthine derivatives (e.g. aminophylline, theophylline), ergometrine, or monoamine oxidase inhibitors. * active nasal/sinus dysfunction (e.g. allergic or infectious rhinitis) or presence of any lesion of the nasal mucosa. * pregnancy, breastfeeding and women of childbearing potential not using a highly effective contraception method. * uncontrolled hypertension, arrhythmia, heart failure, or untreated coronary artery disease. history of transient ischemic attacks, stroke, neurovascular disease, hemorrhage, severe head injury, hydrocephalus or elevated intracranial pressure within the last 3 months. * history of primary or metastatic malignant brain lesions (uncontrolled or without previous treatment). * known aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation * uncontrolled psychiatric illness with psychosis/ hallucination (e.g. schizophrenia, acute psychosis). * alcohol abuse, drug abuse/ dependence within the past 6 months as self-reported. * cirrhosis or severe hepatic impairment defined as 5-fold elevation of transaminases * uncontrolled hyperthyroidism. * globe injuries or increased intraocular pressure (e.g. glaucoma). * history of ulcerative or interstitial cystitis. * subjects scheduled to receive radiotherapy (rt) to a site of pain during the study period, or who have received rt to a site of pain within 2 weeks before study entry. * subjects scheduled to undergo surgical treatment during the study period likely to affect pain. * subjects on or starting chemotherapy if there is a significant expectation of that therapy affecting pain. * subjects who have not provided signed informed consent form. * concomitant use of drugs moderately or severely affecting cytochrome p450 activity.

Keywords: esketamine pain measurement opioid refractory pain