Knee Replacement ArthroplastyPhase 4NCT03954379
IPACK Study in Total Knee Arthroplasty Patients
A Phase 4 study testing IPACK and multi-modal analgesic regimen and Periarticular Local Anesthetic Infiltration in people with Knee Replacement Arthroplasty, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This study proposes to compare current multimodal analgesic treatment for TKA with a new multimodal analgesic regimen to demonstrate decreased opioid requirement, time to rehabilitation, and time to reach hospital discharge. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Knee Replacement Arthroplasty
- What is being tested?
- IPACK and multi-modal analgesic regimen and Periarticular Local Anesthetic Infiltration
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteCanada
- Study dates
- 24 Oct 2019to 31 Mar 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- English-speaking;
- Age 18 - 85;
- BMI ≤ 38;
- Undergoing unilateral primary total knee arthroplasty surgery.
Who cannot join
- inability to give informed consent
- patient refusal
- pregnancy, patients who are breastfeeding
- contraindication to nerve blocks or multimodal analgesia
- contraindication or hypersensitivity to any of the study drugs (celecoxib, acetaminophen, morphine, ropivacaine, bupivacaine, ketamine, dexmedetomidine, dexamethasone, ketorolac, epinephrine, sulfonamides)
- chronic pain disorders (> 50 mg oral morphine equivalence per day at time of recruitment)
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- medical or recreational use of marijuana and substance abuse (e.g., alcoholism),
- complications after surgery that result in discharge to a location other than home
- severe cardiovascular diseases e.g., heart failure, significant dysrhythmias; uncontrolled low blood pressure e.g., systolic blood pressure ≤ 100 mm Hg while on antihypertensive medication(s)
- respiratory diseases e.g., severe asthma, urticaria, or allergic-type reactions after taking acetylsalicylic acid (ASA) or other NSAIDs; severe acute or chronic respiratory disease and obstructive airway
- severe or active liver disease
- severe inflammatory bowel disease
- severe renal impairment (creatinine clearance <30 mL/min)
- uncontrolled diabetes (type 1 or 2)
- active bleeding condition (e.g., postoperative or gastro-intestinal bleeding)
- severe psychiatric disorders and intake of monoamine oxidase inhibitors
- neurologic disorders (e.g., operative extremity neuropathy, delirium tremens, uncontrolled convulsive disorders, increased cerebrospinal or intracranial pressure)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Opioid Sparing Analgesic Strategies for Enhanced Recovery After Total Knee Arthroplasty
This study proposes to compare current multimodal analgesic treatment for TKA with a new multimodal analgesic regimen to demonstrate decreased opioid requirement, time to rehabilitation, and time to reach hospital discharge.
Read the detailed description
Total knee replacement surgery (TKA) causes severe pain and this procedure is the most common reason patients are prescribed strong opioid drugs in hospital. As a result they are slow to begin rehabilitation after surgery, and are late in hospital discharge. Ontario hospitals are constantly challenged to meet growing demands of TKA and in fact increased demand has overcome the health care system resulting in TKA wait time (Ontario actual: 286 days vs. target: 182 days).1 One strategy to accommodate expanding volume and reduce wait time is to reduce hospital length of stay (LOS) through an enhanced recovery program.2 One essential component is further improvement of postoperative pain treatment to expedite rehabilitation and hospital discharge.
Treatment of severe post TKA pain often requires potent opioids but their excessive and prolonged use has negative consequences e.g., increased perioperative adverse events and longer LOS.3 Approximately 8% of opioid naive TKA patients become chronic opioid users at 6 months and the duration of prescription is the strongest predictor of misuse.4 Knowing that the opioid crisis in Canada is steadily growing and prescription opioids play a significant role in dependence and misuse,5 an effective perioperative opioid minimization analgesic program is mandatory for TKA patients.
Current multimodal analgesic treatment for TKA consists of oral non opioid drugs e.g., acetaminophen and non steroidal anti-inflammatory agents (NSAIDs) and surgeon performed peri-articular local anesthesia infiltration, however this is only partially effective.6 The regional analgesic effect is often short lived (< 8 hours). Failure to sustain effective analgesia necessitates continued heavy reliance on opioids.
Several new treatments have been recently described for post TKA pain. They are: IV dexamethasone (steroid),7 dexmedetomidine (alpha 2 agonist)8, ketamine (NMDA antagonist)9 and 2 novel nerve block procedures- adductor canal block10 and iPACK block (infiltration between popliteal artery and posterior capsule of the knee).11 While each individual intervention has demonstrable analgesic benefit, the impact of incorporating all new treatments into the current analgesic regimen remains unknown.
The investigators believe that the new multimodal analgesic regimen proposed in this study will significantly decrease opioid requirement, time to rehabilitation, and time to reach hospital discharge criteria. It may also decrease the duration of opioid prescription for pain relief after hospital discharge. Although investigator's preliminary experience with this new regimen in 10 patients is promising, robust evidence showing its sustained opioid sparing analgesic effect is lacking.
- Conditions
- Knee Replacement Arthroplasty
- Being tested
- Standard of Care (ACB, SA, peri-op pain management), IPACK and multi-modal analgesic regimen, Periarticular Local Anesthetic Infiltration, IV Dexamethasone 8mg at the end of surgery as standard of care
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard of Care (ACB, SA, peri-op pain management)Drug
Also called ACB
INTERVENTION BEFORE SURGERY
Adductor Canal Block will be done using Adductor canal catheter (tube in the thigh) + injection of freezing medication
INTERVENTION DURING SURGERY
IV propofol for sedation
INTERVENTION AFTER SURGERY
Injection of salty water through the tube in the thigh x 2
IPACK and multi-modal analgesic regimenDrug
Also called Infilteration between popliteal artery and posterior capsule of the knee
INTERVENTION BEFORE SURGERY
- Adductor Canal Block will be done using Adductor canal catheter (tube in the thigh) + injection of freezing medication
- iPACK block ( infiltration between Popliteal Artery and posterior Capsule of the Knee) - injection of freezing medication in the back of the knee
INTERVENTION DURING SURGERY
- IV dexmedetomidine
- IV ketamine Both for sedation
INTERVENTION AFTER SURGERY
- injection of freezing medication through the tube in the thigh x 2
- IV dexamethasone 8 mg 1 day after surgery
Periarticular Local Anesthetic InfiltrationProcedure or surgery
Also called LAI
INTERVENTION DURING SURGERY
IV Dexamethasone 8mg at the end of surgery as standard of careDrug
Also called IV Dexamethasone Infusion
INTERVENTION DURING SURGERY
| Study group | Role | What they receive |
|---|---|---|
| Group C ( Comparator Group ) | Active comparator | Standard of care: Adductor Canal Block(ACB), Spinal Anesthesia (SA) and Peri-op Pain management Receives: Drug: Standard of Care (ACB, SA, peri-op pain management); Procedure: Periarticular Local Anesthetic Infiltration; Drug: IV Dexamethasone 8mg at the end of surgery as standard of care |
| Group S ( Study Group ) | Experimental | iPACK and multi-modal analgesic regimen Receives: Drug: IPACK and multi-modal analgesic regimen; Procedure: Periarticular Local Anesthetic Infiltration; Drug: IV Dexamethasone 8mg at the end of surgery as standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
postoperative opioid consumption in MG
Cumulative 24 hour oral hydromorphone and oxycodone equivalent consumption
Measured: 24 hours
Secondary outcomes (7)
Pain scores at rest using numerical rating scale (NRS, 0 to 10)
0, 12, 18, 24, 36 and 48 hours after surgery and also pain scores during physical therapy daily
Measured: 0-48 hours after surgery
Opioid consumption in MG
Analgesic consumption at 12, 18, 36 and 48 hours and 1, 2 and 6 weeks after surgery
Measured: 12 hours to 6 weeks after surgery
Quality of Recovery (QoR) assessed using a validated QoR-15 tool ( Total score range- 0 to 150, higher values represent a better outcome)
Treatment effect will be estimated using a linear regression model, with baseline QoR score as a covariate.
Measured: Baseline, 24-hour, 48-hour and 2-weeks after surgery
Time to reach physical therapy milestones in hours
The post TKA milestones are: knee flexion ≥ 90 degrees, get in and out of bed by self, safe transfer to bathroom with or without assistance, walk with an assistive device on a level surface for a short distance and being able to climb up and down 2 or 3 stairs. steps or flights of stairs?
Measured: 0-72 hours after surgery
Time to reach hospital discharge criteria in hours
The 4 criteria are: 1) adequate analgesia (numerical rating scale <4/10); 2) independence from IV opioids ≥ 12 hours; 3) ability to independently stand and sit down (evaluated with the Timed Up and Go test and 4) unassisted ambulation ≥ 30 mins (evaluated with the 6-min walk test)
Measured: 24 to 72 hours after surgery until discharge
Incidence of adverse events related to nerve block procedures
muscle weakness, systemic toxicity
Measured: Post-op 24 to 72 hours
Incidence of adverse events related to opioid consumption
nausea, vomiting, dizziness, sedation
Measured: Post-op 24 to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start24 Oct 2019
- Primary completion2 Dec 2020
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Knee Replacement ArthroplastyStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vincent Chan, MD, Principal investigator, University Health Network, Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03954379
- Sponsor's protocol ID
- 18-5920
- Status last verified
- Mar 2021
- First submitted
- 16 Apr 2019
- Last updated
- 29 Apr 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opioid Sparing Analgesic Strategies for Enhanced Recovery After Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT03954379
- Acronym / sponsor ID
- 18-5920
- Conditions
- Knee Replacement Arthroplasty
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 2 Dec 2020 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 17 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study proposes to compare current multimodal analgesic treatment for TKA with a new multimodal analgesic regimen to demonstrate decreased opioid requirement, time to rehabilitation, and time to reach hospital discharge.
Detailed description
Total knee replacement surgery (TKA) causes severe pain and this procedure is the most common reason patients are prescribed strong opioid drugs in hospital. As a result they are slow to begin rehabilitation after surgery, and are late in hospital discharge. Ontario hospitals are constantly challenged to meet growing demands of TKA and in fact increased demand has overcome the health care system resulting in TKA wait time (Ontario actual: 286 days vs. target: 182 days).1 One strategy to accommodate expanding volume and reduce wait time is to reduce hospital length of stay (LOS) through an enhanced recovery program.2 One essential component is further improvement of postoperative pain treatment to expedite rehabilitation and hospital discharge.
Treatment of severe post TKA pain often requires potent opioids but their excessive and prolonged use has negative consequences e.g., increased perioperative adverse events and longer LOS.3 Approximately 8% of opioid naive TKA patients become chronic opioid users at 6 months and the duration of prescription is the strongest predictor of misuse.4 Knowing that the opioid crisis in Canada is steadily growing and prescription opioids play a significant role in dependence and misuse,5 an effective perioperative opioid minimization analgesic program is mandatory for TKA patients.
Current multimodal analgesic treatment for TKA consists of oral non opioid drugs e.g., acetaminophen and non steroidal anti-inflammatory agents (NSAIDs) and surgeon performed peri-articular local anesthesia infiltration, however this is only partially effective.6 The regional analgesic effect is often short lived (< 8 hours). Failure to sustain effective analgesia necessitates continued heavy reliance on opioids.
Several new treatments have been recently described for post TKA pain. They are: IV dexamethasone (steroid),7 dexmedetomidine (alpha 2 agonist)8, ketamine (NMDA antagonist)9 and 2 novel nerve block procedures- adductor canal block10 and iPACK block (infiltration between popliteal artery and posterior capsule of the knee).11 While each individual intervention has demonstrable analgesic benefit, the impact of incorporating all new treatments into the current analgesic regimen remains unknown.
The investigators believe that the new multimodal analgesic regimen proposed in this study will significantly decrease opioid requirement, time to rehabilitation, and time to reach hospital discharge criteria. It may also decrease the duration of opioid prescription for pain relief after hospital discharge. Although investigator's preliminary experience with this new regimen in 10 patients is promising, robust evidence showing its sustained opioid sparing analgesic effect is lacking.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group C ( Comparator Group ) | Active comparator | Drug: Standard of Care (ACB, SA, peri-op pain management), Procedure: Periarticular Local Anesthetic Infiltration, Drug: IV Dexamethasone 8mg at the end of surgery as standard of careStandard of care: Adductor Canal Block(ACB), Spinal Anesthesia (SA) and Peri-op Pain management |
| Group S ( Study Group ) | Experimental | Drug: IPACK and multi-modal analgesic regimen, Procedure: Periarticular Local Anesthetic Infiltration, Drug: IV Dexamethasone 8mg at the end of surgery as standard of careiPACK and multi-modal analgesic regimen |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- English-speaking;
- Age 18 - 85;
- BMI ≤ 38;
- Undergoing unilateral primary total knee arthroplasty surgery.
Key exclusion criteria (17 listed)
- inability to give informed consent
- patient refusal
- pregnancy, patients who are breastfeeding
- contraindication to nerve blocks or multimodal analgesia
- contraindication or hypersensitivity to any of the study drugs (celecoxib, acetaminophen, morphine, ropivacaine, bupivacaine, ketamine, dexmedetomidine, dexamethasone, ketorolac, epinephrine, sulfonamides)
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 |
|---|---|---|
| Standard of Care (ACB, SA, peri-op pain management)Also: ACBINTERVENTION BEFORE SURGERY Adductor Canal Block will be done using Adductor canal catheter (tube in the thigh) + injection of freezing medication INTERVENTION DURING SURGERY IV propofol for sedation INTERVENTION AFTER SURGERY Injection of salty water through the tube in the thigh x 2 | Drug | Group C ( Comparator Group ) |
| IPACK and multi-modal analgesic regimenAlso: Infilteration between popliteal artery and posterior capsule of the kneeINTERVENTION BEFORE SURGERY 1. Adductor Canal Block will be done using Adductor canal catheter (tube in the thigh) + injection of freezing medication 2. iPACK block ( infiltration between Popliteal Artery and posterior Capsule of the Knee) - injection of freezing medication in the back of the knee INTERVENTION DURING SURGERY 1. IV dexmedetomidine 2. IV ketamine Both for sedation INTERVENTION AFTER SURGERY 1. injection of freezing medication through the tube in the thigh x 2 2. IV dexamethasone 8 mg 1 day after surgery | Drug | Group S ( Study Group ) |
| Periarticular Local Anesthetic InfiltrationAlso: LAIINTERVENTION DURING SURGERY | Procedure or surgery | Group C ( Comparator Group ), Group S ( Study Group ) |
| IV Dexamethasone 8mg at the end of surgery as standard of careAlso: IV Dexamethasone InfusionINTERVENTION DURING SURGERY | Drug | Group C ( Comparator Group ), Group S ( Study Group ) |
Primary outcome
postoperative opioid consumption in MG
Time frame: 24 hours
Cumulative 24 hour oral hydromorphone and oxycodone equivalent consumption
7 secondary outcomes
Pain scores at rest using numerical rating scale (NRS, 0 to 10)
Time frame: 0-48 hours after surgery
Opioid consumption in MG
Time frame: 12 hours to 6 weeks after surgery
Quality of Recovery (QoR) assessed using a validated QoR-15 tool ( Total score range- 0 to 150, higher values represent a better outcome)
Time frame: Baseline, 24-hour, 48-hour and 2-weeks after surgery
Time to reach physical therapy milestones in hours
Time frame: 0-72 hours after surgery
Time to reach hospital discharge criteria in hours
Time frame: 24 to 72 hours after surgery until discharge
Incidence of adverse events related to nerve block procedures
Time frame: Post-op 24 to 72 hours
Incidence of adverse events related to opioid consumption
Time frame: Post-op 24 to 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
- Individual participant dataSharing planned: No
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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.
Vincent Chan, MD principal investigator
University Health Network, Toronto
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 IPACK and multi-modal analgesic regimen and Periarticular Local Anesthetic Infiltration in people with Knee Replacement Arthroplasty, run by University Health Network, Toronto at 1 site in Canada.
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 4 inclusion and 17 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 29 Apr 2022. 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 Canada. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
postoperative opioid consumption in MG (time frame: 24 hours). 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 29 Apr 2022.