Anesthetic Premedication With a Cannabis Extract (Cannapremed)

Effects of a Cannabis Extract as Anaesthetic Premedication on Postoperative Pain, Nausea-vomiting and Perioperative Anxiety

Sponsors

Lead Sponsor: Hadassah Medical Organization

Collaborator: GW Pharmaceuticals Ltd.

Source 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.

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.

Overall Status Unknown status
Start Date 2015-05-01
Completion Date 2017-02-01
Primary Completion Date 2016-12-01
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Postoperative pain - VAS 24 hours
Postoperative pain - PCA 24 hours
Secondary Outcome
Measure Time Frame
Postoperative nausea and vomiting (PONV) score 24 hours
Anxiety - VAS 6 hours
Cannabinoid blood levels 24 hours
Enrollment 200
Condition
Intervention

Intervention Type: Drug

Intervention Name: Tetrahydrocannabinol

Description: 1:1 THC to CBD standardized extract from cannabis plant

Other Name: Sativex

Intervention Type: Drug

Intervention Name: Acetaminophen

Description: 50 ml intravenous vial

Arm Group Label: Active placebo

Other Name: Paracetamol

Intervention Type: Drug

Intervention Name: Midazolam

Description: 2 ml prefilled syringe

Arm Group Label: Active placebo

Other Name: No other name

Intervention Type: Drug

Intervention Name: Dummy oromucosal spray

Description: Oromucosal spray containing only alcohol vehicle without the active compound (i.e.: without nabiximols)

Other Name: Sativex placebo

Eligibility

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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

60 Years

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Elyad Davidson, M.D. Principal Investigator Hadassah Medical Organization
Overall Contact

Last Name: Carlos A Ibarra Moreno, M.D., Ph.D.

Phone: +972 50 5172881

Email: [email protected]

Location
Facility: Status: Contact: Hasassah - Hebrew University Ein Kerem Medical Center CARLOS A IBARRA MORENO, M.D., Ph.D. +972 50 5172881 [email protected]
Location Countries

Israel

Verification Date

2016-03-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Label: Nabiximols high dose

Type: Experimental

Description: Single-dose, before anesthetic induction: 21.6 mg tetrahydrocannabinol + 20 mg cannabidiol, oromucosal spray. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.

Label: Nabixomols low dose

Type: Experimental

Description: Single-dose, before anesthetic induction: 10.8 mg tetrahydrocannabinol + 10 mg cannabidiol, oromucosal spray. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.

Label: Active placebo

Type: Active Comparator

Description: Single-dose, before anesthetic induction: Dummy oromucosal spray containing alcohol vehicle without nabiximols. Prefilled 50 ml vial containing 1 g acetaminophen, intravenous. Prefilled 2 ml syringe containing 2 mg midazolam, intravenous.

Label: Control

Type: Placebo Comparator

Description: Single-dose, before anesthetic induction: Dummy oromucosal spray containing alcohol vehicle without nabiximols. Dummy 50 ml vial containing 0.9% sodium chloride solution, intravenous. Prefilled dummy 2ml syringe containing 0.9% sodium chloride solution, intravenous.

Acronym Cannapremed
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact [email protected]. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Research News