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Comparison of Treatment by IN Ketamine to IV Morphine in Acute Pain

Sponsor
Tel-Aviv Sourasky Medical Center (Other)
Overall Status
Unknown status
CT.gov ID
NCT03511833
Collaborator
Medical Corps, Israel Defense Force (Other)
120
Enrollment
1
Location
2
Arms
24
Anticipated Duration (Months)
5
Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The procedure:

  1. 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.

  2. Research physician will address the patient, explain about the trial and ask the patient to sign a consent form.

  3. The patient will be randomized and assigned to a trial group: "A" or "B" and it will be noted in the Data sheet.

  4. 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.

  5. 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).

  6. 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

  1. Administration of the medication is limited to one hour from preparation in the syringe.

  2. 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.

  3. 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.

  4. 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.

  1. Measurement of vital signs will not interfere with any other treatment that the patients receives for their injury in the ED.

  2. If the patient will be moved to another department from the ED, they will be withdrawn from the study.

  3. 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.

  4. 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

Study Type:
Interventional
Anticipated Enrollment :
120 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention 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.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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Other
Official Title:
Comparison of Treatment by IN Ketamine to IV Morphine in Acute Pain
Anticipated Study Start Date :
Dec 1, 2019
Anticipated Primary Completion Date :
Dec 1, 2021
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Morphine group

Morphine group will receive IV medication and IN saline.

Drug: Morphine
IV morphine -0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----> 0.1 ml/kg
Other Names:
  • no other Intervention name

    		•
    Experimental: Ketamine group

    Ketamine group will receive IV saline and IN medication.

    Drug: Ketamine
    IN ketamine: 1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---> 0.02ml/kg
    Other Names:
  • no other Intervention name

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Effectiveness of intranasal ketamine in decreasing pain intensity [patient assessed - VAS pain score] [ Time Frame: 2 hour post administration [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.

    Secondary Outcome Measures

    1. • adverse effects [Opiate Related Symptom Distress Scale] [ Time Frame: 2 hour post administration ] [2 hours]

      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.

    2. • patient satisfaction [Interview] [ Time Frame: 2 hours post administration ] [2 hours post administration]

      patients were asked to provide subjective comments

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tel Aviv Sourasky Medical Center, department of Emergency Medicine Tel Aviv Israel 6423906

    Sponsors and Collaborators

    • Tel-Aviv Sourasky Medical Center
    • Medical Corps, Israel Defense Force

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    michal roll, Director, R&D Department, Tel-Aviv Sourasky Medical Center
    ClinicalTrials.gov Identifier:
    NCT03511833
    Other Study ID Numbers:
    • TASMC-18-PH-0459-17-CTIL
    First Posted:
    Apr 30, 2018
    Last Update Posted:
    Jun 25, 2019
    Last Verified:
    Jun 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by michal roll, Director, R&D Department, Tel-Aviv Sourasky Medical Center
    Intra nasal ketamine
    IV morphine
    acute traumatic pain
    Additional relevant MeSH terms:
    Acute Pain
    Ketamine
    Morphine

    Study Results

    No Results Posted as of Jun 25, 2019