Cancer PainPhase 2IMPORTANCENCT04666623
Compare the Efficacy and Safety of Intranasal Esketamine in Chronic Opioid Refractory Pain
A Phase 2 study testing esketamine nasal spray in people with Cancer Pain, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer Pain
- What is being tested?
- esketamine nasal spray
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteSwitzerland
- Study dates
- 25 Nov 2020to 11 Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
Basel, 4031
About this study
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
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
- Being tested
- esketamine nasal spray, placebo nasal spray
- Keywords
- Esketamine, Pain measurement, Opioid refractory pain
- Medical subject headings
- Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
esketamine nasal sprayDrug
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 nasal sprayDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| intranasal esketamine (56mg) | Active comparator | Not described Receives: Drug: esketamine nasal spray |
| placebo | Placebo comparator | Not described Receives: Drug: placebo nasal spray |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 consecutive weeks (from Baseline to week 4)
Secondary outcomes (4)
Rescue morphine use
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.
Measured: 4 consecutive weeks (from Baseline to week 4)
Change in Brief Pain Inventory (BPI)
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.
Measured: 4 consecutive weeks (from Baseline to week 4)
Change in Patient Health Questionnaire (PHQ9)
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).
Measured: 4 consecutive weeks (from Baseline to week 4)
Change in Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
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).
Measured: 4 consecutive weeks (from Baseline to week 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2020
- Study start25 Nov 2020
- Primary completion11 Oct 2023
- Study completion11 Oct 2023
Why it stopped: investigator decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cancer PainStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- placebo-controlled, double-blinded with two parallel groups, superiority trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benito Benitez, MD, Principal investigator, University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04666623
- Sponsor's protocol ID
- ch20Benitez2
- Acronym
- IMPORTANCE
- Status last verified
- Oct 2023
- First submitted
- 2 Dec 2020
- Last updated
- 19 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33732434
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04666623
- Acronym / sponsor ID
- IMPORTANCE / ch20Benitez2
- Conditions
- Cancer Pain
- Keywords
- Esketamine, Pain measurement, Opioid refractory pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: investigator decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 11 Oct 2023 (actual)
- Study completion
- 11 Oct 2023 (actual)
- First posted
- 14 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- placebo-controlled, double-blinded with two parallel groups, superiority trial.
| Arm | Type | Receives |
|---|---|---|
| intranasal esketamine (56mg) | Active comparator | Drug: esketamine nasal spray |
| placebo | Placebo comparator | Drug: placebo nasal spray |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patient with refractory cancer pain, this pain defined when:
- 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.
- 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).
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| esketamine nasal sprayunlabeled 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. | Drug | intranasal esketamine (56mg) |
| placebo nasal sprayunlabeled 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. | Drug | placebo |
Primary outcome
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 secondary outcomes
Rescue morphine use
Time frame: 4 consecutive weeks (from Baseline to week 4)
Change in Brief Pain Inventory (BPI)
Time frame: 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 Side Effect Rating Scale for Dissociative Anesthetics (SERSDA)
Time frame: 4 consecutive weeks (from Baseline to week 4)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2023.
- Derived from this study: PubMed 33732434Fernandes 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benito Benitez, MD principal investigator
University Hospital Basel, Klinik für Mund-, Kiefer- und Gesichtschirurgie
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing esketamine nasal spray in people with Cancer Pain, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the eleven point Numeric Pain Rating Scale (NPRS) (time frame: 4 consecutive weeks (from Baseline to week 4)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04666623, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2023.