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

NCT ID: NCT04666623

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-25
• Study Completion Date: 2023-10-11

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

intranasal esketamine (56mg)

Group Type: ACTIVE_COMPARATOR

esketamine nasal spray

Intervention Type: 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.

placebo

Group Type: PLACEBO_COMPARATOR

placebo nasal spray

Intervention Type: 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.

Interventions

esketamine nasal spray

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.

Intervention Type: DRUG

placebo nasal spray

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benito Benitez, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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

Basel, , Switzerland

Countries

Switzerland

References

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.

Reference Type: DERIVED

PMID: 33732434 (View on PubMed)

Other Identifiers

ch20Benitez2

Identifier Type: -

Identifier Source: org_study_id