Compare the Efficacy and Safety of Intranasal Esketamine in Chronic Opioid Refractory Pain

NCT04666623 | Withdrawn Phase 2 DMC

• 1 other identifier: ch20Benitez2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Cancer Pain

Keywords

Esketamine; Pain measurement; Opioid refractory pain

Outcome Measures

Primary Outcomes (1)

• Change in the eleven point Numeric Pain Rating Scale (NPRS)

  Change in the eleven point Numeric Pain Rating Scale (NPRS): assess pain intensity at enrollment and at each visit. Patients will be asked to rate their weekly pain on a scale from 0 to 10 where 0 equals "no pain" and 10 equals "the worst pain they can imagine. NPRS will be taken for both, during physical activity and at rest.

  4 consecutive weeks (from Baseline to week 4)

Secondary Outcomes (4)

• Rescue morphine use

  4 consecutive weeks (from Baseline to week 4)

• Change in Brief Pain Inventory (BPI)

  4 consecutive weeks (from Baseline to week 4)

• Change in Patient Health Questionnaire (PHQ9)

  4 consecutive weeks (from Baseline to week 4)

• Change in Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)

  4 consecutive weeks (from Baseline to week 4)

Study Arms (2)

intranasal esketamine (56mg)

ACTIVE COMPARATOR

Drug: esketamine nasal spray

placebo

PLACEBO COMPARATOR

Drug: placebo nasal spray

Interventions

esketamine nasal spray DRUG

unlabeled nasal injectors, each device will deliver 28mg of esketamine in a 200 μL solution, so in order to achieve the 56mg dose two devices will be required. On each dosing day during the trial, participants will self-administer at 2 time points 1 spray of the nasal spray into each nostril. Each administration will be separated by 5 minutes. The participants will receive the intervention twice weekly for 4 consecutive weeks.

intranasal esketamine (56mg)

placebo nasal spray DRUG

unlabeled nasal injectors, each device will deliver 28mg of placebo in a 200 μL solution, so in order to achieve the 56mg dose two devices will be required. On each dosing day during the trial, participants will self-administer at 2 time points 1 spray of the nasal spray into each nostril. Each administration will be separated by 5 minutes. The participants will receive the intervention twice weekly for 4 consecutive weeks.

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 33732434 DERIVED

MeSH Terms

Conditions

Cancer Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Benito Benitez, MD

  University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, patients, care providers, outcome assessors, and study statisticians will remain blinded with respect to the treatment allocation. Allocation sequence will be concealed for everyone involved in the trial, except for the pharmacist and the nurse responsible for patient's allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo-controlled, double-blinded with two parallel groups, superiority trial.

Study Record Dates

• First Submitted: December 2, 2020
• First Posted: December 14, 2020
• Study Start: November 25, 2020
• Primary Completion: October 11, 2023
• Study Completion: October 11, 2023
• Last Updated: October 19, 2023

Record last verified: 2023-10

Locations

CH (1)