Pain, PostoperativePhase 4NCT02987920
Dextromethorphan Use in Multimodal Analgesia Regimens for Total Knee Arthroplasty
A Phase 4 study testing Dextromethorphan, Acetaminophen and Oxycodone in people with Pain, Postoperative, run by University of Southern California.
Trial summary
Total knee arthroplasty (TKA) is one of the most painful orthopedic procedures. After TKA surgery, postoperative pain relief may be achieved using a variety of techniques. Integral to recovery and improved outcomes is early ambulation and mobilization. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Postoperative
- What is being tested?
- Dextromethorphan, Acetaminophen and Oxycodone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Jan 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (>18 years of age, American Society of Anesthesiologists (ASA) > IIII) who are undergoing only elective primary total knee replacement will be included in the study.
Who cannot join
- patient refusal to be included in the study, contraindications to regional anesthesia, history of allergy to amide local anesthetics, the presence of a progressive neurological deficit, chronic pain diagnoses, the presence of coagulopathy or infection, or pregnancy.
About this study
Official title: A Randomized Double-blinded Study to Evaluate Preincisional Dextromethorphan in Patients Undergoing Total Knee Arthroplasty and Its Effect on Postoperative Opioid Use
Total knee arthroplasty (TKA) is one of the most painful orthopedic procedures. After TKA surgery, postoperative pain relief may be achieved using a variety of techniques. Integral to recovery and improved outcomes is early ambulation and mobilization. Achieving adequate postoperative pain control while ensuring the ability to ambulate early can be quite challenging.
Currently, in our country there has been a call to address prescription opioid use and abuse due to a nationwide opioid epidemic. In light of this, improving our multimodal analgesic protocol will serve to decrease reliance of opioid medications for pain control. Multimodal analgesia is effective in decreasing total opioid consumption postoperatively. Dextromethorphan is a low-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It has a long history of clinical use with an established safety record. Studies have shown that it has a positive effect as an analgesic.
In order to see if dextromethorphan will decrease opioid use, this study will look at two patient groups undergoing total knee arthroplasty with the same preoperative, intraoperative, and postoperative anesthetic plan with the exception of the addition of dextromethorphan to one groups multimodal analgesic regimen. This study is designed as a double-blinded, randomized, prospective cohort trial.
Read the detailed description
Each subject will receive as part of their standard of care a spinal with sedation for intraoperative anesthesia.
Subjects will be randomly assigned using computer generated allotment. The group designation will be placed in sealed envelopes. The group listed will determine whether or not they will receive dextromethorphan as part of their preoperative preincisional analgesic regimen. Only the pharmacist dispensing the medication will be unblinded. The drug and placebo will then be concealed by the pharmacist and delivered to the patient to ingest in the preoperative area.
Group A: standard preop meds
Group B: standard preop meds + dextromethorphan
The standard preoperative analgesic regimen will include placement of an adductor canal catheter nerve block, acetaminophen 1000mg PO, oxycodone extended release 10mg PO, celecoxib 400mg PO (held if elevated creatinine), and pantoprazole 40mg PO
All blocks will be performed by resident trainees under the supervision of anesthesia regional and acute pain attendings. The continuous adductor canal nerve block will be placed using B-Braun "Contiplex Continuous Peripheral Nerve Block Tray", using 20g catheters.
Intraoperative anesthesia will be performed with spinal injection using local anesthestic only. No opioid will be given intrathecally. Intraoperative sedation will include standard sedation with propofol infusion. Postoperative nausea and vomiting prophylaxis will include ondansetron, propofol infusion, and dexamethasone 0.1mg/kg if not contraindicated. The postoperative recovery room pain protocol will include the following: starting the adductor canal catheter infusion with "On-Q" pump dispensing ropivicaine 0.1% at 4ml/hr, oxycodone 5 10mg po for moderate to severe pain, dilaudid 0.2mg IV q5min up to 2 mg, ketorolac 30mg intravenous (IV) once, and acetaminophen 1000mg intravenous once if greater than 6 hours has elapsed since initial preoperative dose.
Assessments of pain using the VAS pain score will be performed in postanesthesia care unit (PACU) at the time of spinal block cessation by a blinded observer (recovery room nurse), and then subsequently every 4 hours by a registered nurse and documented in the electronic medical record. Initial evaluation for resolution of the spinal blockade will be performed at the 1 hour timepoint in the PACU.
Assessments of opioid administration, will include all medications given and documented in the electronic medical record. The various time points analyzed will include intraoperative, PACU, and daily postoperative morphine equivalents administered to each patient.
Postoperative followup will be done by research personnel blinded to the group distribution. Visual Analog Scale for Pain (VAS Pain) will be performed every 4 hours until discharge.
On postoperative day (POD) #1, all patients will be given the Quality of Recovery (QoR) Questionnaire. This is recovery specific, patient rated questionnaire containing 40 items measuring 5 dimensions. The QoR 40 was specifically designed to measure a patient's health status after surgery and anesthesia, and its completion time generally ranges from 3 to 10 min. The five dimensions measured include: the physical comfort (12 items), emotional state (nine items), physical independence (five items), psychological support (seven items) and pain (seven items). The total score and subscales of the QoR 40 are measured using a five point Likert scale (for positive items: 1 = none of the time, 5 = all of the time; for negative items, the scoring was reversed) and individual scores are then added together, with the minimum score being 40 points and the maximum score being 200 points.
In addition, the study will require home follow up phone calls assessing the occurrence of any possible side effects or complications, pain, and postoperative opioid use. These phone calls will occur at POD#3 after discharge, POD #7, POD #14, and POD#28. Each of these phone assessments will require about 5 minutes of time. Authorized research personnel of the study project will be making the phone calls.
- Conditions
- Pain, Postoperative
- Being tested
- Dextromethorphan, Placebo - Concentrate, Acetaminophen, Oxycodone, Celecoxib
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DextromethorphanDrug
Also called delsym
Additional medication to perioperative analgesic regimen in Group B
Placebo - ConcentrateDrug
Also called placebo, placebos, sugar water
Additional medication to perioperative analgesic regimen to Group A
AcetaminophenDrug
Also called tylenol
Multimodal analgesic regimen to Group A and Group B
OxycodoneDrug
Also called oxycodone extended release, oxycontin
Multimodal analgesic regimen to Group A and Group B
CelecoxibDrug
Also called celebrex
Multimodal analgesic regimen to Group A and Group B
PantoprazoleDrug
Also called protonix
Multimodal analgesic regimen to Group A and Group B
KetorolacDrug
Also called toradol
Multimodal analgesic regimen to Group A and Group B
GabapentinDrug
Also called neurontin
Multimodal analgesic regimen to Group A and Group B
HydromorphoneDrug
Also called dilaudid
Multimodal analgesic regimen to Group A and Group B
| Study group | Role | What they receive |
|---|---|---|
| Placebo - Concentrate | Active comparator | preoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Placebo - Concentrate by mouth.
postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain Receives: Drug: Placebo - Concentrate; Drug: Acetaminophen; Drug: Oxycodone; Drug: Celecoxib; Drug: Pantoprazole; Drug: Ketorolac; Drug: Gabapentin; Drug: Hydromorphone |
| Dextromethorphan | Experimental | preoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Dextromethorphan 60mg tablet
postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain, and dextromethorphan 60mg by mouth twice daily Receives: Drug: Dextromethorphan; Drug: Acetaminophen; Drug: Oxycodone; Drug: Celecoxib; Drug: Pantoprazole; Drug: Ketorolac; Drug: Gabapentin; Drug: Hydromorphone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total amount of postoperative opioid used in first 48 hours after knee replacement.
Measured: 48 hours
Secondary outcomes (1)
VAS pain scores
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2016 (estimated)
- Study startJan 2017
- Primary completionJan 2018
- Study completionJan 2018
Why it stopped: The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe 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
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hanna Schittek, University of Southern California
- Investigators
- Hanna Schittek, MD, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02987920
- Sponsor's protocol ID
- HS-16-00739
- Status last verified
- May 2019
- First submitted
- 30 Nov 2016
- Last updated
- 14 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blinded Study to Evaluate Preincisional Dextromethorphan in Patients Undergoing Total Knee Arthroplasty and Its Effect on Postoperative Opioid Use
- ClinicalTrials.gov ID
- NCT02987920
- Acronym / sponsor ID
- HS-16-00739
- Conditions
- Pain, Postoperative
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 9 Dec 2016 (estimated)
- 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.
Total knee arthroplasty (TKA) is one of the most painful orthopedic procedures. After TKA surgery, postoperative pain relief may be achieved using a variety of techniques. Integral to recovery and improved outcomes is early ambulation and mobilization. Achieving adequate postoperative pain control while ensuring the ability to ambulate early can be quite challenging.
Currently, in our country there has been a call to address prescription opioid use and abuse due to a nationwide opioid epidemic. In light of this, improving our multimodal analgesic protocol will serve to decrease reliance of opioid medications for pain control. Multimodal analgesia is effective in decreasing total opioid consumption postoperatively. Dextromethorphan is a low-affinity noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. It has a long history of clinical use with an established safety record. Studies have shown that it has a positive effect as an analgesic.
In order to see if dextromethorphan will decrease opioid use, this study will look at two patient groups undergoing total knee arthroplasty with the same preoperative, intraoperative, and postoperative anesthetic plan with the exception of the addition of dextromethorphan to one groups multimodal analgesic regimen. This study is designed as a double-blinded, randomized, prospective cohort trial.
Detailed description
Each subject will receive as part of their standard of care a spinal with sedation for intraoperative anesthesia.
Subjects will be randomly assigned using computer generated allotment. The group designation will be placed in sealed envelopes. The group listed will determine whether or not they will receive dextromethorphan as part of their preoperative preincisional analgesic regimen. Only the pharmacist dispensing the medication will be unblinded. The drug and placebo will then be concealed by the pharmacist and delivered to the patient to ingest in the preoperative area.
Group A: standard preop meds
Group B: standard preop meds + dextromethorphan
The standard preoperative analgesic regimen will include placement of an adductor canal catheter nerve block, acetaminophen 1000mg PO, oxycodone extended release 10mg PO, celecoxib 400mg PO (held if elevated creatinine), and pantoprazole 40mg PO
All blocks will be performed by resident trainees under the supervision of anesthesia regional and acute pain attendings. The continuous adductor canal nerve block will be placed using B-Braun "Contiplex Continuous Peripheral Nerve Block Tray", using 20g catheters.
Intraoperative anesthesia will be performed with spinal injection using local anesthestic only. No opioid will be given intrathecally. Intraoperative sedation will include standard sedation with propofol infusion. Postoperative nausea and vomiting prophylaxis will include ondansetron, propofol infusion, and dexamethasone 0.1mg/kg if not contraindicated. The postoperative recovery room pain protocol will include the following: starting the adductor canal catheter infusion with "On-Q" pump dispensing ropivicaine 0.1% at 4ml/hr, oxycodone 5 10mg po for moderate to severe pain, dilaudid 0.2mg IV q5min up to 2 mg, ketorolac 30mg intravenous (IV) once, and acetaminophen 1000mg intravenous once if greater than 6 hours has elapsed since initial preoperative dose.
Assessments of pain using the VAS pain score will be performed in postanesthesia care unit (PACU) at the time of spinal block cessation by a blinded observer (recovery room nurse), and then subsequently every 4 hours by a registered nurse and documented in the electronic medical record. Initial evaluation for resolution of the spinal blockade will be performed at the 1 hour timepoint in the PACU.
Assessments of opioid administration, will include all medications given and documented in the electronic medical record. The various time points analyzed will include intraoperative, PACU, and daily postoperative morphine equivalents administered to each patient.
Postoperative followup will be done by research personnel blinded to the group distribution. Visual Analog Scale for Pain (VAS Pain) will be performed every 4 hours until discharge.
On postoperative day (POD) #1, all patients will be given the Quality of Recovery (QoR) Questionnaire. This is recovery specific, patient rated questionnaire containing 40 items measuring 5 dimensions. The QoR 40 was specifically designed to measure a patient's health status after surgery and anesthesia, and its completion time generally ranges from 3 to 10 min. The five dimensions measured include: the physical comfort (12 items), emotional state (nine items), physical independence (five items), psychological support (seven items) and pain (seven items). The total score and subscales of the QoR 40 are measured using a five point Likert scale (for positive items: 1 = none of the time, 5 = all of the time; for negative items, the scoring was reversed) and individual scores are then added together, with the minimum score being 40 points and the maximum score being 200 points.
In addition, the study will require home follow up phone calls assessing the occurrence of any possible side effects or complications, pain, and postoperative opioid use. These phone calls will occur at POD#3 after discharge, POD #7, POD #14, and POD#28. Each of these phone assessments will require about 5 minutes of time. Authorized research personnel of the study project will be making the phone calls.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo - Concentrate | Active comparator | Drug: Placebo - Concentrate, Drug: Acetaminophen, Drug: Oxycodone, Drug: Celecoxib, Drug: Pantoprazole, Drug: Ketorolac, Drug: Gabapentin, Drug: Hydromorphonepreoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Placebo - Concentrate by mouth. postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain |
| Dextromethorphan | Experimental | Drug: Dextromethorphan, Drug: Acetaminophen, Drug: Oxycodone, Drug: Celecoxib, Drug: Pantoprazole, Drug: Ketorolac, Drug: Gabapentin, Drug: Hydromorphonepreoperative oral medications given one time: acetaminophen 1000mg tablet, oxycodone extended release 10mg tablet, celecoxib 400mg tablet, pantoprazole 40mg tablet, and Dextromethorphan 60mg tablet postoperative medications given for 2 days: Acetaminophen 1000mg every 6hr, Ketorolac15mg IV q6hrs x4 doses, Oxycodone 5mg po q3hrs prn moderate pain, Oxycodone10mg po q3hrs prn severe pain, Gabapentin100-300mg once at night, Dilaudid 0.2mg IV q2hrs prn severe pain, and dextromethorphan 60mg by mouth twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients (>18 years of age, American Society of Anesthesiologists (ASA) > IIII) who are undergoing only elective primary total knee replacement will be included in the study.
Key exclusion criteria (1 listed)
- patient refusal to be included in the study, contraindications to regional anesthesia, history of allergy to amide local anesthetics, the presence of a progressive neurological deficit, chronic pain diagnoses, the presence of coagulopathy or infection, or pregnancy.
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 |
|---|---|---|
| DextromethorphanAlso: delsymAdditional medication to perioperative analgesic regimen in Group B | Drug | Dextromethorphan |
| Placebo - ConcentrateAlso: placebo, placebos, sugar waterAdditional medication to perioperative analgesic regimen to Group A | Drug | Placebo - Concentrate |
| AcetaminophenAlso: tylenolMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| OxycodoneAlso: oxycodone extended release, oxycontinMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| CelecoxibAlso: celebrexMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| PantoprazoleAlso: protonixMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| KetorolacAlso: toradolMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| GabapentinAlso: neurontinMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
| HydromorphoneAlso: dilaudidMultimodal analgesic regimen to Group A and Group B | Drug | Dextromethorphan, Placebo - Concentrate |
Primary outcome
Total amount of postoperative opioid used in first 48 hours after knee replacement.
Time frame: 48 hours
1 secondary outcome
VAS pain scores
Time frame: 28 days
Results and safety
The study was stopped early (reason given: The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2019.
- 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.
Hanna Schittek, MD principal investigator
University of Southern California
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dextromethorphan, Acetaminophen and Oxycodone in people with Pain, Postoperative, run by University of Southern California.
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 1 inclusion and 1 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: stopped early, as of the sponsor's last update on 14 May 2019. Status can change between updates, so confirm with the study contact before making plans.
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 was stopped early (reason given: The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.). Results are not available in the source record.
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?
Total amount of postoperative opioid used in first 48 hours after knee replacement. (time frame: 48 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 14 May 2019.