Acute Traumatic PainPhase 3NCT03511833
Comparison of Treatment by IN Ketamine to IV Morphine in Acute Pain
A Phase 3 study testing Morphine and Ketamine in people with Acute Traumatic Pain, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
Patients who present with acute traumatic injuries in the pre-hospital setting or to the emergency department (ED) are treated with opioids, the current gold standard for severe acute pain therapy. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acute Traumatic Pain
- What is being tested?
- Morphine and Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteIsrael
- Study dates
- Dec 2019to Dec 2021
- Phase
- Phase 3
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- be 18-70 years old
- self-report pain greater than or equal to 7/10 on a numerical-verbal scale
- weigh 50-100 kg
- have an ASA (American Society of Anaesthesiologists' classification) score of 1-2
- have systolic blood pressure of 90-160 mmHg
Who cannot join
- have had opioid analgesia administered within 2 hours of the study
- are chronic analgesia users (of opioid or others)
- have known allergies to morphine or ketamine
- have had a large meal within an hour prior to trauma
- are pregnant
- have a psychiatric history
- have nasal congestion, nasal trauma, epistaxis, or a deviated nasal septum
- have suffered any head or face trauma: any trauma that is manifested by an external mark in the face or skull.
Trial locations and contacts
1 site in 1 country.
Israel1 site
Tel Aviv Sourasky Medical Center, department of Emergency Medicine
Tel Aviv, 6423906
Pinchas Halpern, MD, 972-3-6973829, dr_halperin@tasmc.health.gov.il
Daniel Trotzky, MD, +972507308675, danieltro@tlvmc.gov.il
About this study
Patients who present with acute traumatic injuries in the pre-hospital setting or to the emergency department (ED) are treated with opioids, the current gold standard for severe acute pain therapy. Treatment with opioids has many disadvantages: the need of skilled manpower to administer the medication IV, numerous side effects- mainly cardiorespiratory depression- which necessitates post medication administration continuous monitoring of patients. IV administration may be difficult or impossible to provide in a number of extreme circumstances. For these reasons, there is a constant search for alternate treatment options for pain in acute traumatic injuries. IN ketamine has only recently been studied favorably in our department in adults, in an open, prospective study (Shimonovich at al 2016), and warrants further investigation in the setting of acute traumatic pain. Ketamine is a safe and efficacious analgesic and is overall well received both by patients and physicians. Side effects include: hallucinations and dissociation. As opposed to opioids, ketamine does not alter patients' respiratory and hemodynamic stability giving ketamine great therapeutic potential for pain reduction in trauma patients, pre-hospital patients, and battlefield injuries. The study we are conducting is designed to test and analyze the safety and efficacy of IN Ketamine compared to IV morphine in a setting of acute traumatic pain in the ED, when both medications are administered by the protocol as is customary for treatment of pain in the Emergency Medicine department, and will be a prospective, randomized, double blind, controlled study.
Read the detailed description
The procedure:
- Eligible patients will be identified by the ED personnel. They will make sure to inquire about and also visually inspect the patient's nares regarding nasal congestion, deviated septum, obstruction or injury.
- Research physician will address the patient, explain about the trial and ask the patient to sign a consent form.
- The patient will be randomized and assigned to a trial group: "A" or "B" and it will be noted in the Data sheet.
- According to physician order (IV amount and IN amount) and patient group assignment, the nurse will prepare two blinded syringes that will be marked "A" or "B" (the assigned group) and "IN" or "IV" and note in the data sheet the time of syringe preparation.
- The IV syringe will contain either Morphine or Normal Saline (up to 10 ml), and the IN syringe will contain either Ketamine or Normal saline (up to 2 ml).
- The amount in the syringes will be calculated based on the patients' weight: IV-0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----> 0.1 ml/kg IN-1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---> 0.02ml/kg
- Administration of the medication is limited to one hour from preparation in the syringe.
- The nurse will hand the syringes to the researcher (blinded and coded) and note in the data sheet the time of administration and the amount to administer IN and IV.
- Prior to administering medication to the patient the researcher will measure vital signs (blood pressure, heart rate, respiratory rate, and O2 saturation) as well as pain level on a 100 mm VAS (visual analogue scale) questionnaire.
- After administration of medications the researcher will measure vital signs (blood pressure, heart rate, respiratory rate, and O2 saturation) as well as pain level on a 100 mm VAS questionnaire every 5 minutes for the first 30 minutes and then every 15 minutes after that at 30, 45, 60, and 90 minutes. Saturation >95% on room air; if lower than 90%, the patient will be placed on 40% oxygen mask.
- Measurement of vital signs will not interfere with any other treatment that the patients receives for their injury in the ED.
- If the patient will be moved to another department from the ED, they will be withdrawn from the study.
- Cardiorespiratory follow-up (as per bullet point number 8 above), will be concluded at 1.5 hours post-intervention, and clinical follow-up will continue as long as the patient remains in the ED.
- 90 minutes after drug administration, if pain had not subsided sufficiently according to treating physician's clinical assessment, patient will receive further analgesic medications by physician order, as per ED protocol. The protocol takes into account concurrent medications (in this case either morphine or ketamine. Neither morphine nor ketamine will be used in these patients after test drug administration.
- Conditions
- Acute Traumatic Pain
- Keywords
- Intra nasal ketamine, IV morphine, acute traumatic pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
Also called no other Intervention name
IV morphine -0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----> 0.1 ml/kg
KetamineDrug
Also called no other Intervention name
IN ketamine: 1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---> 0.02ml/kg
| Study group | Role | What they receive |
|---|---|---|
| Morphine group | Active comparator | Morphine group will receive IV medication and IN saline. Receives: Drug: Morphine |
| Ketamine group | Experimental | Ketamine group will receive IV saline and IN medication. Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score] [ Time Frame: 2 hour post administration
Time to achieve a clinically meaningful pain reduction was defined as the first time-point at which the patient reported 15mm of pain reduction or more. Maximal pain reduction was defined as the lowest VAS score reported by the patient over the course of follow-up. Time to maximal pain reduction was defined as the time at which the patient has the lowest VAS score over the course of the 2 hours follow-up.
Measured: 2 hours
Secondary outcomes (2)
• adverse effects [Opiate Related Symptom Distress Scale] [ Time Frame: 2 hour post administration ]
Adverse effects were recorded at the end of two hours using the 'Opiate Related Symptom Distress Scale' and included measurements of the presence, frequency, intensity and disruptiveness of 12 common opiate side-effects. Among these were nausea, vomiting, urinary retention, constipation, difficulty concentrating, dizziness, confusion, and others.
Measured: 2 hours
• patient satisfaction [Interview] [ Time Frame: 2 hours post administration ]
patients were asked to provide subjective comments
Measured: 2 hours post administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2018
- Study startDec 2019 (estimated)
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Traumatic PainStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe 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 3
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible patients will be randomized according to a blocked randomization scheme using www.sealedenvelope.com (site accessed Sep 10, 2017), which permits assignment of the participant to either group "A" or "group B" (the IN ketamine or IV morphine group). Only the pharmacy will have knowledge of which group is Ketamine and which group is Morphine. Eligible patients will be divided in equal proportions (58 in group A and 58 in group B). Both medications will be prepared by the pharmacy as coded kits, and will be stored in the ER safe with clear signage: "For ketamine/morphine clinical trial only". Shelf life of the kits is 6 months. Each vial in a kit will be marked by the group name either "A" or "B" and by either "IN" or "IV". The "IV" vials will either contain: morphine (10 mg of morphine in 10 ml saline) or 10 ml saline for IV administration, and the "IN" vials will either contain ketamine (100 mg in 2ml saline) or 2 ml saline for nasal administration.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Medical Corps, Israel Defense Force
- Responsible party
- Principal investigator, michal roll, Tel-Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03511833
- Sponsor's protocol ID
- TASMC-18-PH-0459-17-CTIL
- Status last verified
- Jun 2019
- First submitted
- 5 Mar 2018
- Last updated
- 25 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: a table summering pain assessing questioners will be available from corresponding author on reasonable request.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Treatment by IN Ketamine to IV Morphine in Acute Pain
- ClinicalTrials.gov ID
- NCT03511833
- Acronym / sponsor ID
- TASMC-18-PH-0459-17-CTIL
- Conditions
- Acute Traumatic Pain
- Keywords
- Intra nasal ketamine, IV morphine, acute traumatic pain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Medical Corps, Israel Defense Force
- Study start
- Dec 2019 (estimated)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 30 Apr 2018 (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.
Patients who present with acute traumatic injuries in the pre-hospital setting or to the emergency department (ED) are treated with opioids, the current gold standard for severe acute pain therapy. Treatment with opioids has many disadvantages: the need of skilled manpower to administer the medication IV, numerous side effects- mainly cardiorespiratory depression- which necessitates post medication administration continuous monitoring of patients. IV administration may be difficult or impossible to provide in a number of extreme circumstances. For these reasons, there is a constant search for alternate treatment options for pain in acute traumatic injuries. IN ketamine has only recently been studied favorably in our department in adults, in an open, prospective study (Shimonovich at al 2016), and warrants further investigation in the setting of acute traumatic pain. Ketamine is a safe and efficacious analgesic and is overall well received both by patients and physicians. Side effects include: hallucinations and dissociation. As opposed to opioids, ketamine does not alter patients' respiratory and hemodynamic stability giving ketamine great therapeutic potential for pain reduction in trauma patients, pre-hospital patients, and battlefield injuries. The study we are conducting is designed to test and analyze the safety and efficacy of IN Ketamine compared to IV morphine in a setting of acute traumatic pain in the ED, when both medications are administered by the protocol as is customary for treatment of pain in the Emergency Medicine department, and will be a prospective, randomized, double blind, controlled study.
Detailed description
The procedure:
- Eligible patients will be identified by the ED personnel. They will make sure to inquire about and also visually inspect the patient's nares regarding nasal congestion, deviated septum, obstruction or injury.
- Research physician will address the patient, explain about the trial and ask the patient to sign a consent form.
- The patient will be randomized and assigned to a trial group: "A" or "B" and it will be noted in the Data sheet.
- According to physician order (IV amount and IN amount) and patient group assignment, the nurse will prepare two blinded syringes that will be marked "A" or "B" (the assigned group) and "IN" or "IV" and note in the data sheet the time of syringe preparation.
- The IV syringe will contain either Morphine or Normal Saline (up to 10 ml), and the IN syringe will contain either Ketamine or Normal saline (up to 2 ml).
- The amount in the syringes will be calculated based on the patients' weight: IV-0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----> 0.1 ml/kg IN-1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---> 0.02ml/kg
- Administration of the medication is limited to one hour from preparation in the syringe.
- The nurse will hand the syringes to the researcher (blinded and coded) and note in the data sheet the time of administration and the amount to administer IN and IV.
- Prior to administering medication to the patient the researcher will measure vital signs (blood pressure, heart rate, respiratory rate, and O2 saturation) as well as pain level on a 100 mm VAS (visual analogue scale) questionnaire.
- After administration of medications the researcher will measure vital signs (blood pressure, heart rate, respiratory rate, and O2 saturation) as well as pain level on a 100 mm VAS questionnaire every 5 minutes for the first 30 minutes and then every 15 minutes after that at 30, 45, 60, and 90 minutes. Saturation >95% on room air; if lower than 90%, the patient will be placed on 40% oxygen mask.
- Measurement of vital signs will not interfere with any other treatment that the patients receives for their injury in the ED.
- If the patient will be moved to another department from the ED, they will be withdrawn from the study.
- Cardiorespiratory follow-up (as per bullet point number 8 above), will be concluded at 1.5 hours post-intervention, and clinical follow-up will continue as long as the patient remains in the ED.
- 90 minutes after drug administration, if pain had not subsided sufficiently according to treating physician's clinical assessment, patient will receive further analgesic medications by physician order, as per ED protocol. The protocol takes into account concurrent medications (in this case either morphine or ketamine. Neither morphine nor ketamine will be used in these patients after test drug administration.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Eligible patients will be randomized according to a blocked randomization scheme using www.sealedenvelope.com (site accessed Sep 10, 2017), which permits assignment of the participant to either group "A" or "group B" (the IN ketamine or IV morphine group). Only the pharmacy will have knowledge of which group is Ketamine and which group is Morphine. Eligible patients will be divided in equal proportions (58 in group A and 58 in group B). Both medications will be prepared by the pharmacy as coded kits, and will be stored in the ER safe with clear signage: "For ketamine/morphine clinical trial only". Shelf life of the kits is 6 months. Each vial in a kit will be marked by the group name either "A" or "B" and by either "IN" or "IV". The "IV" vials will either contain: morphine (10 mg of morphine in 10 ml saline) or 10 ml saline for IV administration, and the "IN" vials will either contain ketamine (100 mg in 2ml saline) or 2 ml saline for nasal administration.
| Arm | Type | Receives |
|---|---|---|
| Morphine group | Active comparator | Drug: MorphineMorphine group will receive IV medication and IN saline. |
| Ketamine group | Experimental | Drug: KetamineKetamine group will receive IV saline and IN medication. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- be 18-70 years old
- self-report pain greater than or equal to 7/10 on a numerical-verbal scale
- weigh 50-100 kg
- have an ASA (American Society of Anaesthesiologists' classification) score of 1-2
- have systolic blood pressure of 90-160 mmHg
Key exclusion criteria (8 listed)
- have had opioid analgesia administered within 2 hours of the study
- are chronic analgesia users (of opioid or others)
- have known allergies to morphine or ketamine
- have had a large meal within an hour prior to trauma
- are pregnant
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 |
|---|---|---|
| MorphineAlso: no other Intervention nameIV morphine -0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----> 0.1 ml/kg | Drug | Morphine group |
| KetamineAlso: no other Intervention nameIN ketamine: 1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---> 0.02ml/kg | Drug | Ketamine group |
Primary outcome
Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score] [ Time Frame: 2 hour post administration
Time frame: 2 hours
Time to achieve a clinically meaningful pain reduction was defined as the first time-point at which the patient reported 15mm of pain reduction or more. Maximal pain reduction was defined as the lowest VAS score reported by the patient over the course of follow-up. Time to maximal pain reduction was defined as the time at which the patient has the lowest VAS score over the course of the 2 hours follow-up.
2 secondary outcomes
• adverse effects [Opiate Related Symptom Distress Scale] [ Time Frame: 2 hour post administration ]
Time frame: 2 hours
• patient satisfaction [Interview] [ Time Frame: 2 hours post administration ]
Time frame: 2 hours post administration
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2019.
- Individual participant dataSharing planned: Yes. a table summering pain assessing questioners will be available from corresponding author on reasonable request.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Morphine and Ketamine in people with Acute Traumatic Pain, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
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 5 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 25 Jun 2019. 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 Israel. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Pinchas Halpern, MD (+97236973829, DR_HALPERIN@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score] [ Time Frame: 2 hour post administration (time frame: 2 hours). 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 25 Jun 2019.