Clinical trial NCT04666623: Compare the Efficacy and Safety of Intranasal Esketamine in Chronic Opioid Refractory Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Cancer Pain
Keywords: Esketamine
Pain measurement
Opioid refractory pain
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2020-12-14
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: placebo-controlled, double-blinded with two parallel groups, superiority trial.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change in the eleven point Numeric Pain Rating Scale (NPRS)
timeFrame: 4 consecutive weeks (from Baseline to week 4)
Secondary outcomes:
measure: Rescue morphine use
timeFrame: 4 consecutive weeks (from Baseline to week 4)
measure: Change in Brief Pain Inventory (BPI)
timeFrame: 4 consecutive weeks (from Baseline to week 4)
measure: Change in Patient Health Questionnaire (PHQ9)
timeFrame: 4 consecutive weeks (from Baseline to week 4)
measure: Change in Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
timeFrame: 4 consecutive weeks (from Baseline to week 4)
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
Study officials:
affiliation: University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
name: Benito Benitez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fernandes M, Schelotto M, Doldi PM, Milani G, Ariza Manzano AA, Perera Valdivia D, Winter Matos AM, Hamdy Abdelrahim Y, Hamad Bek SA, Benitez BK, Romanelli Tavares VL, Basendwah AM, Albuquerque Sousa LH, Xavier NF, Zertuche Maldonado T, Toyomi de Oliveira S, Chaker M, Menon Miyake M, Uygur Kucukseymen E, Waqar K, Alkhozondar OMJ, Bernardo da Silva R, Droppelmann G, Vaz de Macedo A, Nakamura R, Fregni F. 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.