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

NCT ID: NCT03511833

Last Updated: 2019-06-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-31
• Study Completion Date: 2021-12-31

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.

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

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

8. 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.

9. 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.

10. 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.

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

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 If the patient will be moved to another department from the ED, they will be withdrawn from the study.

13. 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.

14. 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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Morphine group

Morphine group will receive IV medication and IN saline.

Group Type: ACTIVE_COMPARATOR

Morphine

Intervention Type: DRUG

IV morphine -0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----\> 0.1 ml/kg

Ketamine group

Ketamine group will receive IV saline and IN medication.

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

IN ketamine: 1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---\> 0.02ml/kg

Interventions

Morphine

IV morphine -0.1 mg/kg: Morphine vial contains 10 mg/10 ml = 1mg/ml ----\> 0.1 ml/kg

Intervention Type: DRUG

Ketamine

IN ketamine: 1 mg/kg: Ketamine vial contains 100 mg/2 ml = 50mg/ml ---\> 0.02ml/kg

Intervention Type: DRUG

Other Intervention Names

no other Intervention name; no other Intervention name

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical Corps, Israel Defense Force

OTHER

Sponsor Role: collaborator

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

michal roll

Director, R&D Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Tel Aviv Sourasky Medical Center, department of Emergency Medicine

Tel Aviv, , Israel

Countries

Israel

Central Contacts

Pinchas Halpern, MD

Role: CONTACT

DR_HALPERIN@tlvmc.gov.il

+97236973829

Daniel Trotzky, MD

Role: CONTACT

danieltro@tlvmc.gov.il

+972507308675

Facility Contacts

Pinchas Halpern, MD

Role: primary

dr_halperin@tasmc.health.gov.il

972-3-6973829

Daniel Trotzky, MD

Role: backup

danieltro@tlvmc.gov.il

+972507308675

Other Identifiers

TASMC-18-PH-0459-17-CTIL

Identifier Type: -

Identifier Source: org_study_id