PainPhase 4NCT04947085
Comparison of Nebulized Ketamine to Intravenous Sub-Dissociative Dose Ketamine for Pain
A Phase 4 study testing Ketamine via Intravenous and Ketamine via BAN in people with Pain, run by Antonios Likourezos at 1 site in United States.
Trial summary
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA)/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization, hyperalgesia, and "wind-up" phenomenon at the level of the spinal cord (dorsal ganglion) and central nervous system (1). Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Pain
- What is being tested?
- Ketamine via Intravenous and Ketamine via BAN
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Oct 2021to 31 Dec 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ED patients
- Patients 18 years of age
- acute and chronic painful conditions
- pain with a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale.
- Patients will have to be awake, alert, and oriented to person, place, and time,
- Be able to demonstrate understanding of the informed consent process and content.
- Patients also will have to demonstrate ability to verbalize the nature of any adverse effects they might experience as well as to express their pain severity by using the NRS.
Who cannot join
- Altered mental status,
- allergy to ketamine,
- pregnant patients,
- weight greater than 150 kg,
- unstable vital signs (systolic blood pressure <90 or>180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
- inability to provide consent,
- past medical history of alcohol or drug abuse, or schizophrenia.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of Nebulized Ketamine to Intravenous Sub-Dissociative Dose Ketamine for Treating Acute and Chronic Painful Conditions in the ED: A Prospective, Randomized, Double-Blind, Double-Dummy Clinical Trial.
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA)/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization, hyperalgesia, and "wind-up" phenomenon at the level of the spinal cord (dorsal ganglion) and central nervous system (1). Ketamine administration in sub-dissociative doses (SDK) of 0.1-0.3 mg/kg in pre-hospital settings and in the ED results in effective pain relief in patients with acute traumatic and non-traumatic pain, chronic non-cancer and cancer pain, and in patients with opioid-tolerant pain by virtue of providing anti-hyperalgesia, anti-allodynia, and anti-tolerance (2-4). Two commonly utilized routes of SDK administration in the ED include an intravenous route (intravenous push dose or short infusion) and intranasal route.
In the situation when intravenous access is not readily available or unobtainable, and intranasal route is not feasible, another non-invasive route of ketamine administration such as inhalation via Breath-Actuated Nebulizer (BAN) is coming into the play. The BAN allows a controlled patient-initiated delivery of analgesics in titratable fashion. Nebulized administration of ketamine has been studied in the areas of acute postoperative pain management (post-intubational sore throat), in anesthesia (pre-medication for general anesthesia,) and in managing cancer pain, and status asthmaticus therapy.
Read more
However, our research team has published a case series of 5 patients receiving nebulized ketamine for a variety of acute painful conditions and has recently completed a randomized double-blind trial of 120 adult patients that evaluated analgesic efficacy and safety of nebulized ketamine at three different dosing regimens for acute pain in the ED. Currently, we are conducting two additional studies evaluating the role of nebulized ketamine in pediatric ED and pre-hospital arena.
In this study the investigators hypothesize that intravenous sub-dissociative-dose ketamine of 0.3 mg/kg will provide better analgesia at 30 min post-medication administration in comparison to nebulized ketamine administered at 0.75 mg/kg. The primary outcome of this trial is the comparative reduction in participant's pain scores at 30 minutes post medication administration.
Read the detailed description
Design: This is a prospective, randomized, double-blind, double dummy trial comparing analgesic efficacy and safety of intravenous SDK administered at 0.3 mg/kg over 15 minutes to nebulized ketamine at 0.75mg/kg administered via BAN to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. Upon meeting the eligibility criteria, patients will be randomized into two study groups: IV SDK and Nebulized K-BAN.
Subjects: Patients 18 years of age and older presenting to the ED with acute and chronic painful conditions such as traumatic and non-traumatic abdominal, flank, back, musculoskeletal pain, headache, as well as exacerbation of chronic abdominal, musculoskeletal and neuropathic pain with a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale and requiring parenteral analgesia as determined by the treating attending physician. Patients' screening and enrollment will be performed by study investigators and research assistants. All patients will be enrolled at various times of the day when study investigators will be available for patient enrollment and an ED pharmacist will be available for medication preparation
Data Collection Procedures: Each patient will be approached by a study investigator for acquisition of written informed consent and Health Insurance Portability and Accountability Act authorization after being evaluated by the treating emergency physician and determined to meet study eligibility criteria. When English will not be the participant's primary language, a language- appropriate consent form will be used and non-investigator, hospital-employed, trained interpreters or licensed telephone interpreter will assist in acquisition of informed consent. Baseline pain score will be determined with an 11-point numeric rating scale (0 to 10), described to the patient as "no pain" being 0 and "the worst pain imaginable" being 10. A study investigator will record the patient's body weight and baseline vital signs.
The on-duty ED pharmacist will prepare either a breath-actuated nebulizer with a dose of 0.75 mg/kg or an infusion dose of IV SDK at 0.3 mg/kg in 100 ml normal saline bag according to the predetermined randomization list, which will be created in SPSS (version 24; IBM Corp, Armonk, NY) with block randomization of every 10 participants. All participants will receive a corresponding placebo in order to maintain double-dummy design: the subjects randomized to receive IV SDK will also receive nebulized saline via BAN, and the subjects receiving K-BAN will also receive an IV infusion of Normal Saline over 15 minutes. The medication will be delivered to the treating nurse in a blinded fashion who will set up an infusion pump with a run time of 15 minutes. The nebulization of active drug and placebo via BAN will have a minimum time of 5 min and maximum time of 15 min.
Study investigators will record pain scores, vital signs, and adverse effects at 15, 30, 60, 90, and 120 minutes. If patients reported a pain numeric rating scale score of 5 or greater and requested additional pain relief, intravenous morphine at 0.1 mg/kg will be administered as a rescue analgesic.
The preparing ED pharmacist, research manager, and statistician will be the only ones with knowledge of the study arm to which each participant would be randomized. Treating providers, participants, and the data collecting research team will be blind to the medication route received.
All data will be recorded on data collection sheets, including patients' sex, demographics, medical history, and vital signs, and entered into SPSS (version 24.0; IBM Corp) by the research manager. Development of the randomization list, confirmation of written consent acquisition for all participants, and statistical analyses will be conducted by the research administrator and/or statistician who will work independently of any data collection.
Patients will be closely monitored for any change in vital sings and for adverse effects during the entire study period (up to 120 minutes) by study investigators. Common adverse effects that are associated with sub-dissociative dose ketamine are felling of unreality, dizziness, nausea, vomiting, and sedation.
- Conditions
- Pain
- Being tested
- Ketamine via Intravenous, Ketamine via BAN
- Medical subject headings
- Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketamine via IntravenousDrug
Ketamine administration in sub-dissociative doses
Ketamine via BANDrug
Ketamine administered via Breath-Actuated Nebulizer (BAN)
| Study group | Role | What they receive |
|---|---|---|
| IV SDK | Active comparator | intravenous ketamine administration in sub-dissociative doses (SDK) administered at 0.3 mg/kg over 15 minutes to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. Receives: Drug: Ketamine via Intravenous |
| K-BAN | Active comparator | nebulized ketamine at 0.75mg/kg administered via BAN to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. Receives: Drug: Ketamine via BAN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in in Pain Score at 30 Minutes
The primary outcome of this trial is the comparative change in participant's pain scores at 30 minutes post medication administration. Pain score is measured in a 11 point Likert Scale where 0 is no pain and 10 is extreme pain; 5 is moderate pain.
Measured: 30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2021
- Study start4 Oct 2021
- Primary completion30 Sep 2023
- Study completion31 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PainStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Antonios Likourezos
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Antonios Likourezos, Maimonides Medical Center
- Investigators
- Sergey Motov, MD, Principal investigator, Maimonides Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04947085
- Sponsor's protocol ID
- 2020-08-05
- Status last verified
- Nov 2023
- First submitted
- 23 Jun 2021
- Last updated
- 3 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Nebulized Ketamine to Intravenous Sub-Dissociative Dose Ketamine for Treating Acute and Chronic Painful Conditions in the ED: A Prospective, Randomized, Double-Blind, Double-Dummy Clinical Trial.
- ClinicalTrials.gov ID
- NCT04947085
- Acronym / sponsor ID
- 2020-08-05
- Conditions
- Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Antonios LikourezosUniversity, hospital or other
- Study start
- 4 Oct 2021 (actual)
- Primary completion
- 30 Sep 2023 (actual)
- Study completion
- 31 Dec 2023 (actual)
- First posted
- 1 Jul 2021 (actual)
- Results
- Posted 3 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA)/glutamate receptor complex antagonist that decreases pain by diminishing central sensitization, hyperalgesia, and "wind-up" phenomenon at the level of the spinal cord (dorsal ganglion) and central nervous system (1). Ketamine administration in sub-dissociative doses (SDK) of 0.1-0.3 mg/kg in pre-hospital settings and in the ED results in effective pain relief in patients with acute traumatic and non-traumatic pain, chronic non-cancer and cancer pain, and in patients with opioid-tolerant pain by virtue of providing anti-hyperalgesia, anti-allodynia, and anti-tolerance (2-4). Two commonly utilized routes of SDK administration in the ED include an intravenous route (intravenous push dose or short infusion) and intranasal route.
In the situation when intravenous access is not readily available or unobtainable, and intranasal route is not feasible, another non-invasive route of ketamine administration such as inhalation via Breath-Actuated Nebulizer (BAN) is coming into the play. The BAN allows a controlled patient-initiated delivery of analgesics in titratable fashion. Nebulized administration of ketamine has been studied in the areas of acute postoperative pain management (post-intubational sore throat), in anesthesia (pre-medication for general anesthesia,) and in managing cancer pain, and status asthmaticus therapy.
However, our research team has published a case series of 5 patients receiving nebulized ketamine for a variety of acute painful conditions and has recently completed a randomized double-blind trial of 120 adult patients that evaluated analgesic efficacy and safety of nebulized ketamine at three different dosing regimens for acute pain in the ED. Currently, we are conducting two additional studies evaluating the role of nebulized ketamine in pediatric ED and pre-hospital arena.
In this study the investigators hypothesize that intravenous sub-dissociative-dose ketamine of 0.3 mg/kg will provide better analgesia at 30 min post-medication administration in comparison to nebulized ketamine administered at 0.75 mg/kg. The primary outcome of this trial is the comparative reduction in participant's pain scores at 30 minutes post medication administration.
Detailed description
Design: This is a prospective, randomized, double-blind, double dummy trial comparing analgesic efficacy and safety of intravenous SDK administered at 0.3 mg/kg over 15 minutes to nebulized ketamine at 0.75mg/kg administered via BAN to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. Upon meeting the eligibility criteria, patients will be randomized into two study groups: IV SDK and Nebulized K-BAN.
Subjects: Patients 18 years of age and older presenting to the ED with acute and chronic painful conditions such as traumatic and non-traumatic abdominal, flank, back, musculoskeletal pain, headache, as well as exacerbation of chronic abdominal, musculoskeletal and neuropathic pain with a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale and requiring parenteral analgesia as determined by the treating attending physician. Patients' screening and enrollment will be performed by study investigators and research assistants. All patients will be enrolled at various times of the day when study investigators will be available for patient enrollment and an ED pharmacist will be available for medication preparation
Data Collection Procedures: Each patient will be approached by a study investigator for acquisition of written informed consent and Health Insurance Portability and Accountability Act authorization after being evaluated by the treating emergency physician and determined to meet study eligibility criteria. When English will not be the participant's primary language, a language- appropriate consent form will be used and non-investigator, hospital-employed, trained interpreters or licensed telephone interpreter will assist in acquisition of informed consent. Baseline pain score will be determined with an 11-point numeric rating scale (0 to 10), described to the patient as "no pain" being 0 and "the worst pain imaginable" being 10. A study investigator will record the patient's body weight and baseline vital signs.
The on-duty ED pharmacist will prepare either a breath-actuated nebulizer with a dose of 0.75 mg/kg or an infusion dose of IV SDK at 0.3 mg/kg in 100 ml normal saline bag according to the predetermined randomization list, which will be created in SPSS (version 24; IBM Corp, Armonk, NY) with block randomization of every 10 participants. All participants will receive a corresponding placebo in order to maintain double-dummy design: the subjects randomized to receive IV SDK will also receive nebulized saline via BAN, and the subjects receiving K-BAN will also receive an IV infusion of Normal Saline over 15 minutes. The medication will be delivered to the treating nurse in a blinded fashion who will set up an infusion pump with a run time of 15 minutes. The nebulization of active drug and placebo via BAN will have a minimum time of 5 min and maximum time of 15 min.
Study investigators will record pain scores, vital signs, and adverse effects at 15, 30, 60, 90, and 120 minutes. If patients reported a pain numeric rating scale score of 5 or greater and requested additional pain relief, intravenous morphine at 0.1 mg/kg will be administered as a rescue analgesic.
The preparing ED pharmacist, research manager, and statistician will be the only ones with knowledge of the study arm to which each participant would be randomized. Treating providers, participants, and the data collecting research team will be blind to the medication route received.
All data will be recorded on data collection sheets, including patients' sex, demographics, medical history, and vital signs, and entered into SPSS (version 24.0; IBM Corp) by the research manager. Development of the randomization list, confirmation of written consent acquisition for all participants, and statistical analyses will be conducted by the research administrator and/or statistician who will work independently of any data collection.
Patients will be closely monitored for any change in vital sings and for adverse effects during the entire study period (up to 120 minutes) by study investigators. Common adverse effects that are associated with sub-dissociative dose ketamine are felling of unreality, dizziness, nausea, vomiting, and sedation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IV SDK | Active comparator | Drug: Ketamine via Intravenousintravenous ketamine administration in sub-dissociative doses (SDK) administered at 0.3 mg/kg over 15 minutes to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. |
| K-BAN | Active comparator | Drug: Ketamine via BANnebulized ketamine at 0.75mg/kg administered via BAN to patients presenting to the ED of Maimonides Medical Center with acute and chronic painful conditions. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ED patients
- Patients 18 years of age
- acute and chronic painful conditions
- pain with a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale.
- Patients will have to be awake, alert, and oriented to person, place, and time,
Key exclusion criteria (7 listed)
- Altered mental status,
- allergy to ketamine,
- pregnant patients,
- weight greater than 150 kg,
- unstable vital signs (systolic blood pressure <90 or>180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
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 |
|---|---|---|
| Ketamine via IntravenousKetamine administration in sub-dissociative doses | Drug | IV SDK |
| Ketamine via BANKetamine administered via Breath-Actuated Nebulizer (BAN) | Drug | K-BAN |
Primary outcome
Change in in Pain Score at 30 Minutes
Time frame: 30 minutes
The primary outcome of this trial is the comparative change in participant's pain scores at 30 minutes post medication administration. Pain score is measured in a 11 point Likert Scale where 0 is no pain and 10 is extreme pain; 5 is moderate pain.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Sergey Motov, MD principal investigator
Maimonides Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine via Intravenous and Ketamine via BAN in people with Pain, run by Antonios Likourezos at 1 site in United States.
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 7 inclusion and 7 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: finished, as of the sponsor's last update on 3 Jul 2024. 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 United States. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 in Pain Score at 30 Minutes (time frame: 30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Jul 2024.