- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04666623
Compare the Efficacy and Safety of Intranasal Esketamine in Chronic Opioid Refractory Pain (IMPORTANCE)
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Benito Benitez, MD
- Phone Number: +41 61 556 52 85
- Email: benito.benitez@usb.ch
Study Locations
-
-
-
Basel, Switzerland, 4031
- University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
-
Contact:
- Benito Benitez, MD
- Phone Number: +41 61 556 52 85
- Email: benito.benitez@usb.ch
-
Principal Investigator:
- Benito Benitez, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: placebo
|
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.
|
Active Comparator: intranasal esketamine (56mg)
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in the eleven point Numeric Pain Rating Scale (NPRS)
Time Frame: 4 consecutive weeks (from Baseline to week 4)
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rescue morphine use
Time Frame: 4 consecutive weeks (from Baseline to week 4)
|
The use of morphine rescue (whether it will be reduced, no change, or increased).
This will be monitored using either the Aircure artificial intelligence through a mobile application or personal diaries.
|
4 consecutive weeks (from Baseline to week 4)
|
Change in Brief Pain Inventory (BPI)
Time Frame: 4 consecutive weeks (from Baseline to week 4)
|
Patients' functional status and satisfaction will be measured by the change in Brief Pain Inventory (BPI).
(0 = no pain; 10 = pain as bad as you can imagine); No scoring algorithm, but "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity; the arithmetic mean of the seven interference items can be used as a measure of pain interference.
|
4 consecutive weeks (from Baseline to week 4)
|
Change in Patient Health Questionnaire (PHQ9)
Time Frame: 4 consecutive weeks (from Baseline to week 4)
|
Change in depression score using the Patient Health Questionnaire (PHQ9) at enrollment and at each visit.
It scores each of the nine depression criteria as "0" (not at all) to "3" (nearly every day).
|
4 consecutive weeks (from Baseline to week 4)
|
Change in Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
Time Frame: 4 consecutive weeks (from Baseline to week 4)
|
Change in Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) at enrollment and at each visit.
It assesses fatigue, dizziness, headache, nausea, changes in vision and mood changes (0 = side effects absent and 4 = adverse effect is bothersome).
|
4 consecutive weeks (from Baseline to week 4)
|
Collaborators and Investigators
Investigators
- Principal Investigator: Benito Benitez, MD, University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ch20Benitez2
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cancer Pain
-
Kyowa Kirin Co., Ltd.Completed
-
University Hospital, Basel, SwitzerlandTerminatedCancer: Breakthrough Pain | Cancer: Extreme Pain on MovementSwitzerland
-
University of UtahCompletedCancer-associated PainUnited States
-
University of JordanCompleted
-
Laboratoires Bouchara-RecordatiUnknown
-
University of PittsburghCompletedMetastatic Cancer | Invasive Cancer | Pain, CancerUnited States
-
Wex Pharmaceuticals Inc.Completed
-
Sorrento Therapeutics, Inc.WithdrawnPain, Intractable | Pain Cancer
-
Kyowa Kirin Co., Ltd.Completed
Clinical Trials on esketamine nasal spray
-
Lukas PezawasRecruitingMajor Depressive Disorder | Therapy Resistant DepressionAustria
-
Janssen Research & Development, LLCCompletedDepressive Disorder, Treatment-ResistantUnited States, France, Poland, United Kingdom, Belgium, Germany, Taiwan, Spain, Argentina, Mexico, Bulgaria, Malaysia, South Africa, Turkey, Canada, Korea, Republic of, Brazil, Estonia, Hungary, Lithuania, Slovakia, Sweden, Czechia, A... and more
-
Medical University InnsbruckWithdrawn
-
Royal North Shore HospitalJanssen-Cilag Pty LtdRecruitingMajor Depressive DisorderAustralia
-
Rupert LanzenbergerCompleted
-
University of North Carolina, Chapel HillRecruitingDepressive Disorder, MajorUnited States
-
VistaGen Therapeutics, Inc.TerminatedSocial Anxiety DisorderUnited States
-
VistaGen Therapeutics, Inc.RecruitingSocial Anxiety DisorderUnited States
-
VistaGen Therapeutics, Inc.CompletedSocial Anxiety DisorderUnited States
-
University of ChicagoMcNeil Consumer & Specialty Pharmaceuticals, a Division of McNeil-PPC, Inc.Withdrawn