Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Anesthetic Premedication With a Cannabis Extract (Cannapremed) (Cannapremed)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02283281
Recruitment Status : Unknown
Verified March 2016 by Hadassah Medical Organization.
Recruitment status was:  Recruiting
First Posted : November 5, 2014
Last Update Posted : March 24, 2016
Sponsor:
Collaborator:
GW Pharmaceuticals Ltd.
Information provided by (Responsible Party):
Hadassah Medical Organization

Brief Summary:

Clinical evidence about the effects of cannabis in a perioperative setting or for the management of acute pain is rather scarce, mostly consisting of case report-based opinions on adverse events during or after general anesthesia after smoking cannabis, experimental pain trials in healthy volunteers, and a few clinical trials using different drugs, dosages and routes of administration. It is difficult to draw strong conclusions from the available evidence, that may seem sometimes even contradictory, mainly due -the investigators believe- to the many sources of variability in the study designs (e.g.: heterogeneity of the study samples, underpowered, unblinding, lack of randomization, timing of the therapeutic intervention, different experimental pain models, inclusion of different kind of surgical pain, etc.). Nevertheless, expert's opinion after a critical review of the literature is that cannabis and cannabinoids may have a beneficial role in the management of acute post-operative pain and nausea, at least for a selected group of patients and through an appropriate therapeutic intervention.

Therefore, it seems to us pertinent to carry out an investigation in order to re-evaluate the issue of perioperative cannabis use through a sufficiently powered and controlled clinical trial. Some of cannabis effects such as sedation, bronchodilation, dryness of respiratory secretions, vein dilation, and increase of heart rater without producing hypertension, make of it an attractive option for pre-medication; while its antiemetic properties and its analgesic potential without causing respiratory depression may be profitable for the post-operative period.

Nabiximols seem to be most suitable to our investigation. The co-administration of tetrahydrocannabinol (THC) with cannabidiol (CBD) may translate into additional therapeutic benefits with an attenuation of adverse effects. The investigators expect to obtain less sedation, milder "high", lower incidence of anxiety, tachycardia, and hyperalgesia, as compared with THC-only acute pain trials.


Condition or disease Intervention/treatment Phase
Pain, Postoperative Postoperative Nausea and Vomiting Anxiety Drug: Tetrahydrocannabinol Drug: Acetaminophen Drug: Midazolam Drug: Dummy oromucosal spray Phase 2 Phase 3

Detailed Description:

The selection of patients will be done during the pre-anesthetic assessment the day before surgery. After obtaining informed consent, eligible patients will be randomly allocated to one of the following regimes: nabiximols high dose (21.6 mg THC + 20 mg CBD), nabiximols low dose (10.8 mg THC + 10 mg CBD), active placebo (prefilled syringe with 1 mg midazolam + 1 g acetaminophen I.V.), placebo control (no premedication drugs).

Treatments will be administered in a double-dummy manner. Identical bottles of Sativex® and placebo should be obtained from the manufacturer (GW Pharmaceuticals). Identical prefilled vials containing either the active placebo (1 mg midazolam + 1 g acetaminophen) or sodium chloride 0.9% should be prepared by the hospital pharmacist. To the best of our knowledge, no clinical studies evaluating the effects of nabiximols on acute pain or in a perioperative setting have been done to date. Therefore, the investigators estimate a Sativex® dose range that seems reasonable to obtain relevant clinical and a manageable occurrence of adverse events, mainly based on the recommendations from the manufacturer, on the available pharmacological data presented in the previous section and on the results of other clinical trials with a similar design using comparable doses of oral THC. Nevertheless, the first 10 patients will be randomly assigned either to the nabiximols low dose group or to the placebo control group only. The investigators will proceed with the full four-group randomization only if no serious adverse events are registered among the 10 first recruited patients.

At the arrival to the operating room, blood samples for baseline levels of cannabinoids will be drawn at the moment of placing the intravenous line, and the first anxiety assessment should be done by the examiner/anesthetist. The study drugs will be administered at the entrance to the O.R. or at the induction room 15 minutes before the induction of anesthesia (i.e.:). Premedication dose should be calculated to be the equivalent of 10 mg and 20 mg oral THC for the low and high dose groups, respectively (4, 8 puffs). At the same time, the prefilled syringe containing either 1 mg midazolam + 1 g acetaminophen or sodium chloride 0.9% will be administered as intravenous bolus. The patients will be immediately connected to the standard O.R. monitoring.

Induction of general anaesthesia will be done in a standardized fashion with fentanyl 2 µg/Kg, propofol 1-4 mg/Kg (and vecuronium 0.1 mg/Kg if intubation is required). For anaesthetic maintenance, isoflurane 0.7-2% on 1:2 oxygen : nitrous oxide gas mixture, and fentanyl boluses 1 µg/Kg to keep a bispectral index (BIS) between 40 to 60, and a heart rate and mean arterial pressure between 70-130% from pre-induction baselines. Preemptive antiemetics (e.g.: granisetron, ondansetron, metoclopramide, dexamethasone, etc.) should not be given. No additional analgesics should be administered (e.g.: ketorolac or other NSAID's, dipyrone).

A loading dose of morphine 0.2 mg/Kg will be given before the end of surgery provided that the patient can maintain spontaneous breathing or pressure support ventilation. Intravenous morphine patient-controlled analgesia (PCA) will be initiated on the arrival to the recovery room with boluses of 1 mg and a lockout time of 6 minutes, without background.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of a Cannabis Extract as Anaesthetic Premedication on Postoperative Pain, Nausea-vomiting and Perioperative Anxiety
Study Start Date : May 2015
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : February 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nabiximols high dose

Single-dose, before anesthetic induction:

  1. 21.6 mg tetrahydrocannabinol + 20 mg cannabidiol, oromucosal spray.
  2. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous.
  3. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.
Drug: Tetrahydrocannabinol
1:1 THC to CBD standardized extract from cannabis plant
Other Name: Sativex

Experimental: Nabixomols low dose

Single-dose, before anesthetic induction:

  1. 10.8 mg tetrahydrocannabinol + 10 mg cannabidiol, oromucosal spray.
  2. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous.
  3. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.
Drug: Tetrahydrocannabinol
1:1 THC to CBD standardized extract from cannabis plant
Other Name: Sativex

Active Comparator: Active placebo

Single-dose, before anesthetic induction:

  1. Dummy oromucosal spray containing alcohol vehicle without nabiximols.
  2. Prefilled 50 ml vial containing 1 g acetaminophen, intravenous.
  3. Prefilled 2 ml syringe containing 2 mg midazolam, intravenous.
Drug: Acetaminophen
50 ml intravenous vial
Other Name: Paracetamol

Drug: Midazolam
2 ml prefilled syringe
Other Name: No other name

Drug: Dummy oromucosal spray
Oromucosal spray containing only alcohol vehicle without the active compound (i.e.: without nabiximols)
Other Name: Sativex placebo

Placebo Comparator: Control

Single-dose, before anesthetic induction:

  1. Dummy oromucosal spray containing alcohol vehicle without nabiximols.
  2. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous.
  3. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.
Drug: Dummy oromucosal spray
Oromucosal spray containing only alcohol vehicle without the active compound (i.e.: without nabiximols)
Other Name: Sativex placebo




Primary Outcome Measures :
  1. Postoperative pain - VAS [ Time Frame: 24 hours ]
    Self-reported visual analog scale (VAS 0 - 100 mm) at rest and on movement. Pre-operative baseline, on arrival to recovery room, after 1 h, before discharge, at 6, 12, and 24 h.

  2. Postoperative pain - PCA [ Time Frame: 24 hours ]

    Count of patient-controlled analgesia pushes 1 hour after arrival to the recovery room, before discharge, at 6, and 12.

    Total dose of morphine received in 24 hours.



Secondary Outcome Measures :
  1. Postoperative nausea and vomiting (PONV) score [ Time Frame: 24 hours ]

    PONV score (0 - 4) on arrival to recovery room, after 1 hour, before discharge, at 6, 12, and 24 hours.

    0. No nausea

    1. Nausea sometimes
    2. Nausea most of the time
    3. Dry retching or vomiting
    4. Dry retching or vomiting twice or more

  2. Anxiety - VAS [ Time Frame: 6 hours ]
    Self-assessed anxiety visual analog scale (0-100 mm) on arrival to the OR; on arrival to and before discharge from recovery room.

  3. Cannabinoid blood levels [ Time Frame: 24 hours ]
    Blood sampling from arterial line inserted on arrival to the OR before the main premedication dose, after 30 min, at 1, 3, 6, 12, and 24 hours.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients scheduled for elective surgeries suitable for postoperative pain treatment with intravenous morphine patient-controlled analgesia.
  • American Society of Anesthesiologist (ASA) risk I or II

Exclusion Criteria:

  • ASA III or higher
  • Cannabis use within the last 6 months
  • Pregnancy
  • Emergency surgeries
  • Regional anesthesia
  • Ischemic heart disease
  • Renal failure
  • History of psychosis
  • Cognitive impairment or inability to answer questions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02283281


Contacts
Layout table for location contacts
Contact: Carlos A Ibarra Moreno, M.D., Ph.D. +972 50 5172881 olimsj@gmail.com
Contact: Charles Weissman, M.D. +972-2-677-7269 charles@hadassah.org.il

Locations
Layout table for location information
Israel
Hasassah - Hebrew University Ein Kerem Medical Center Recruiting
Jerusalem, Israel, 12000
Contact: CARLOS A IBARRA MORENO, M.D., Ph.D.    +972 50 5172881    olimsj@gmail.com   
Sponsors and Collaborators
Hadassah Medical Organization
GW Pharmaceuticals Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Elyad Davidson, M.D. Hadassah Medical Organization

Layout table for additonal information
Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT02283281     History of Changes
Other Study ID Numbers: Cannapremed-HMO-CTIL
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: March 24, 2016
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Layout table for MeSH terms
Nausea
Vomiting
Pain, Postoperative
Postoperative Nausea and Vomiting
Signs and Symptoms, Digestive
Signs and Symptoms
Postoperative Complications
Pathologic Processes
Pain
Neurologic Manifestations
Acetaminophen
Midazolam
Dronabinol
Nabiximols
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Adjuvants, Anesthesia
Hypnotics and Sedatives
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Non-Narcotic
Analgesics