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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.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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
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.

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 groups in NCT02987920
Study groupRoleWhat they receive
Placebo - ConcentrateActive comparatorpreoperative 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
DextromethorphanExperimentalpreoperative 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.

  1. Total amount of postoperative opioid used in first 48 hours after knee replacement.

    Measured: 48 hours

Secondary outcomes (1)
  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.

  1. First posted9 Dec 2016 (estimated)
  2. Study startJan 2017
  3. Primary completionJan 2018
  4. Study completionJan 2018

Why it stopped: The surgeon changed pain control protocol for all patients. Continued enrollment impossible under approved protocol.

Resources

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)
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

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.

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