Pain, PostoperativePhase 4NCT04749628
Cannabidiol for Bilateral Total Knee Arthroplasty
A Phase 4 study testing cannabidiol and Ora-sweet SF in people with Pain, Postoperative and Opioid Use, run by Hospital for Special Surgery, New York at 1 site in United States.
Trial summary
In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pain, Postoperative, Opioid Use, Knee Osteoarthritis
- What is being tested?
- cannabidiol and Ora-sweet SF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Nov 2022to 8 Jan 2025
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 75
- Scheduled for same-day bilateral total knee replacements with participating surgeons
- American Society of Anesthesiologists (ASA) Physical Status 1 or 2
Who cannot join
- ASA 3 and higher
- Weight < 40kg
- Planned use of general anesthesia
- Contraindication to major components of study protocol
- Cannabis or cannabinoid use within the past 3 months (recreational and/or medical)
- Use or ingestion of hemp seeds or hemp oil in any form within the past 30 days
Show all 21Show fewer
- Chronic opioid use (>3 months)
- Coumadin use
- Current use of SSRI or SNRIs
- History of substance abuse or dependence
- Active or history of major psychiatric illness
- Severe cardiovascular disorder
- Severe hepatic or renal insufficiency (transaminase levels above ULN)
- History of epilepsy
- Diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, etc.)
- Use of valproate or clobazam
- Known or suspected hypersensitivity, allergy, or contraindication to cannabinoids or any of the excipients in the study medications (i.e. sesame oil, sucralose, strawberry flavor)
- Active use of steroids - oral steroids upon admission
- Stress dose steroids
- Non-English speakers
- Planned discharge to home without caregiver(s)
Trial locations and contacts
1 site in 1 country.
United States1 site
Hospital for Special Surgery
New York, New York, 10021
About this study
Official title: Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study
In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Epidiolex®, an oral cannabidiol (CBD) solution, is the first ever cannabis-derived medication to be approved by the Food \& Drug Administration. Our aim is to conduct a pilot study using a placebo oral solution, 400mg and 800mg Epidiolex® to gather data on its effects on patients undergoing bilateral total knee arthroplasty (BTKA). We will be estimating whether Epidiolex® is associated with minimal opioid use and adequate analgesia. We will also assess its tolerability, pharmacokinetics, and effects on inflammatory markers in the perioperative setting.
- Conditions
- Pain, Postoperative, Opioid Use, Knee Osteoarthritis
- Being tested
- cannabidiol, Ora-sweet SF
- Medical subject headings
- Pain, Postoperative, Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cannabidiolDrug
Also called Epidiolex
Epidiolex (cannabidiol) oral solution
Ora-sweet SFOther
Ora-sweet SF placebo
| Study group | Role | What they receive |
|---|---|---|
| Ora-sweet SF | Placebo comparator | Not described Receives: Other: Ora-sweet SF |
| 400mg cannabidiol | Experimental | Not described Receives: Drug: cannabidiol |
| 800mg cannabidiol | Experimental | Not described Receives: Drug: cannabidiol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Opioid Usage in First 72 Hours Postoperatively
Cumulative opioid usage over the first 72 hours after surgery. Measured in morphine equivalents (ME), a scale that measure opioid usage among all opioid medications
Measured: 0-72 hours postoperatively
Secondary outcomes (19)
Pharmacokinetics of CBD
Levels of CBD in the blood. This is measured using blood draws and lab analysis.
Measured: 0, 1, 2, 3, 4, 6 hours after medication administration
Levels of Plasma Inflammatory Marker Interleukin-6
Interleukin-6 (IL6) is an inflammatory marker found in plasma. The levels of IL6 are measured using blood draws and lab analysis.
The outcome measure below indicates the difference between IL6 levels on postoperative day 1 and preoperative.
Measured: Preoperative, Postoperative day 1
NRS Pain at Rest
Pain at rest measured using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.
Measured: Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
NRS Pain With Movement
Pain with movement using numerical rating scale(NRS) from 0-10, with 0 being no pain at all to 10 being the worst pain imaginable.
Measured: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Brief Pain Inventory Short Form
Brief Pain inventory short form measures the severity of pain and its impact on function. It measures pain from 0-10 0 being no pain whatsoever to 10 being the worst pain imaginable. It measures impact on function from 0-10, 0 being no impact whatsoever to 10 being completely impactful.
Measured: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Incidence of Adverse Events
Adverse events, including allergic reactions, pyrexia (fever), somnolence (excessive sleepiness), GI problems (upset stomach, diarrhea), dry mouth, escalation of post-operative opioid requirement
Measured: Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Opioid Related Symptom Distress Scale (ORSDS)
Opioid related Symptom Distress Scale (ORSDS) measures opioid related side effects. There are 12 side effects with 3 subcategories (severity, frequency, bothersomeness) each with 5 different responses (scored 0-4 with higher scores indicating worse symptoms). The ORSDS composite score was calculated by averaging the scores for each symptom.
Measured: Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Anxiety Levels
Hospital Anxiety and Depression Scale (HADS) asks 14 questions, 7 about anxiety and 7 about depression. Responses are scored from 0-3. Responses between the two categories are summed and scoring is as follows: 0-7 = normal, 8-10=borderlines abnormal, 11-21=abnormal
Measured: Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Cumulative Inpatient Analgesic Use (Non-opioid)
Total non-opioid medication usage
Measured: POD0 - POD3
Number of Participants With Opioid and Non-opioid Medication Use
Opioid and non-opioid medication use by count (%)
Measured: POD0 - POD3
Opioid & Non-opioid Analgesic Consumption
Total opioid (morphine milligram equivalents) \& non-opioid medication usage
Measured: At hospital discharge to POD7
Number of Participants With Opioid and Non-opioid Medication Use
Opioid \& non-opioid medication use by count (%)
Measured: POD0 to POD7 and 3 months
Hospital Length of Stay
Length of stay measured in hours from end of surgery to hospital discharge
Measured: At hospital discharge
Blinding Assessment
Patients are asked which treatment they think they received. The correctness of their guesses is then measured using the bang-blinding index to see if patients were able to accurately guess which treatment they received. It is measured on a scale of -1 to 1. Scores closer to 0 indicate better blinding, or patients not being able to guess their treatment. The index (number) is calculated as a group-level summary statistic, computed from the distribution of guesses across all participants in a group.
Measured: POD4
Time to Reach Discharge Physical Therapy Goals
Physical therapy goals for total knee replacement include walking 100 feet, going up and down 4 stairs, and independent transfer (meaning they can move from a lying to standing position independently). Patients need to complete these goals before being discharged
Measured: At hospital discharge
Range of Motion
Range of motion, or extension and flexion of the knees, are measured preoperatively and at the patients' 6 week surgeon visit. It is measured in degrees
Measured: preoperatively, 6 weeks postoperatively.
Actigraphy Sleep Efficiency
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep efficiency indicates better sleep quality. Sleep efficiency was calculated between the hours of 11pm and 6am each night.
Measured: POD0 - POD3
Actigraphy Sleep Time
Sleep quality assessed by actigraphy using ActiGraph wGT3X-BT activity monitor. Higher sleep time indicates better sleep quality. Total sleep time was calculated between the hours of 11pm and 6am each night.
Measured: POD0 - POD3
Sleep Quality
Sleep quality assessed by Leeds sleep evaluation questionnaire (LSEQ). Responses to 10 questions will be measured on a slider scale ranging from 0-100. Higher scores indicate better outcomes.
Getting to Sleep domain scores were calculated by averaging the responses to Questions 1-3 regarding falling asleep.
Quality of Sleep domain scores were calculated by averaging the responses to Questions 4-5 regarding quality of sleep.
Awake Following Sleep domain scores were calculated by averaging the responses to Questions 6-7 regarding awakening from sleep.
Behaviour Following Wakening domain scores were calculated by averaging the responses to Questions 8-10 regarding feeling, balance, and coordination upon awakening.
Measured: preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2021
- Study start2 Nov 2022
- Primary completion11 Oct 2024
- Study completion8 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital for Special Surgery, New York
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alexandra Sideris, PhD, Principal investigator, Hospital for Special Surgery, New York
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04749628
- Sponsor's protocol ID
- 2019-1688
- Status last verified
- Oct 2024
- First submitted
- 5 Feb 2021
- Last updated
- 26 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Cannabidiol (CBD) Oral Solution in Patients Undergoing Bilateral Total Knee Arthroplasty: a Randomized, Controlled, Parallel, Triple Blind, Pilot Study
- ClinicalTrials.gov ID
- NCT04749628
- Acronym / sponsor ID
- 2019-1688
- Conditions
- Pain, Postoperative, Opioid Use, Knee Osteoarthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Hospital for Special Surgery, New YorkUniversity, hospital or other
- Study start
- 2 Nov 2022 (actual)
- Primary completion
- 11 Oct 2024 (actual)
- Study completion
- 8 Jan 2025 (actual)
- First posted
- 11 Feb 2021 (actual)
- Results
- Posted 26 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Epidiolex®, an oral cannabidiol (CBD) solution, is the first ever cannabis-derived medication to be approved by the Food \& Drug Administration. Our aim is to conduct a pilot study using a placebo oral solution, 400mg and 800mg Epidiolex® to gather data on its effects on patients undergoing bilateral total knee arthroplasty (BTKA). We will be estimating whether Epidiolex® is associated with minimal opioid use and adequate analgesia. We will also assess its tolerability, pharmacokinetics, and effects on inflammatory markers in the perioperative setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ora-sweet SF | Placebo comparator | Other: Ora-sweet SF |
| 400mg cannabidiol | Experimental | Drug: cannabidiol |
| 800mg cannabidiol | Experimental | Drug: cannabidiol |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18 to 75
- Scheduled for same-day bilateral total knee replacements with participating surgeons
- American Society of Anesthesiologists (ASA) Physical Status 1 or 2
Key exclusion criteria (21 listed)
- ASA 3 and higher
- Weight < 40kg
- Planned use of general anesthesia
- Contraindication to major components of study protocol
- Cannabis or cannabinoid use within the past 3 months (recreational and/or medical)
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 |
|---|---|---|
| cannabidiolAlso: EpidiolexEpidiolex (cannabidiol) oral solution | Drug | 400mg cannabidiol, 800mg cannabidiol |
| Ora-sweet SFOra-sweet SF placebo | Other | Ora-sweet SF |
Primary outcome
Cumulative Opioid Usage in First 72 Hours Postoperatively
Time frame: 0-72 hours postoperatively
Cumulative opioid usage over the first 72 hours after surgery. Measured in morphine equivalents (ME), a scale that measure opioid usage among all opioid medications
19 secondary outcomes
Pharmacokinetics of CBD
Time frame: 0, 1, 2, 3, 4, 6 hours after medication administration
Levels of Plasma Inflammatory Marker Interleukin-6
Time frame: Preoperative, Postoperative day 1
NRS Pain at Rest
Time frame: Preoperatively; postoperatively in the PACU, morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
NRS Pain With Movement
Time frame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Brief Pain Inventory Short Form
Time frame: Preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Incidence of Adverse Events
Time frame: Postoperatively in the PACU; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Opioid Related Symptom Distress Scale (ORSDS)
Time frame: Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Anxiety Levels
Time frame: Preoperatively; Morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Cumulative Inpatient Analgesic Use (Non-opioid)
Time frame: POD0 - POD3
Number of Participants With Opioid and Non-opioid Medication Use
Time frame: POD0 - POD3
Opioid & Non-opioid Analgesic Consumption
Time frame: At hospital discharge to POD7
Number of Participants With Opioid and Non-opioid Medication Use
Time frame: POD0 to POD7 and 3 months
Hospital Length of Stay
Time frame: At hospital discharge
Blinding Assessment
Time frame: POD4
Time to Reach Discharge Physical Therapy Goals
Time frame: At hospital discharge
Range of Motion
Time frame: preoperatively, 6 weeks postoperatively.
Actigraphy Sleep Efficiency
Time frame: POD0 - POD3
Actigraphy Sleep Time
Time frame: POD0 - POD3
Sleep Quality
Time frame: preoperatively; morning of postoperative day (POD) 1,2,3,4,7 and at 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices) will be shared.
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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.
Alexandra Sideris, PhD principal investigator
Hospital for Special Surgery, New York
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing cannabidiol and Ora-sweet SF in people with Pain, Postoperative and Opioid Use, run by Hospital for Special Surgery, New York at 1 site in United States.
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 3 inclusion and 21 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: finished, as of the sponsor's last update on 26 May 2026. 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 United States. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Opioid Usage in First 72 Hours Postoperatively (time frame: 0-72 hours postoperatively). 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 26 May 2026.