What side effects are associated with this type of intervention?

Common treatments for postoperative pain, such as Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) like duloxetine, can cause side effects including nausea, dry mouth, dizziness, insomnia, constipation, and fatigue. There is also a potential risk for increased blood pressure and heart rate. Other treatments, such as opioids, may lead to sedation, constipation, nausea, vomiting, and respiratory depression, while nonsteroidal anti-inflammatory drugs (NSAIDs) can cause gastrointestinal issues, renal impairment, and increased bleeding risk.

What prior FDA approvals exist?

Duloxetine, an SNRI, has been studied for its potential in managing postoperative pain, particularly in the context of total knee arthroplasty. While duloxetine itself is not specifically FDA-approved for postoperative pain, it is approved for chronic musculoskeletal pain, which includes conditions like osteoarthritis and chronic low back pain. Other SNRIs, such as venlafaxine, have also been explored for pain management, including neuropathic pain. Additionally, tricyclic antidepressants like amitriptyline and nortriptyline, which share some pharmacological properties with SNRIs, have been used off-label for various types of pain, including postoperative pain. These drugs work by modulating neurotransmitters involved in pain perception, providing a broader context for their use in pain management.

What other types of research exist?

Promising novel alternatives to Duloxetine for postoperative pain management include: 1) Ketamine, which has shown efficacy in alleviating pain and depression in chronic pain patients. 2) Psilocybin, which has demonstrated rapid and sustained symptom reduction in anxiety and depression, potentially beneficial for postoperative pain. 3) Pregabalin, which has been effective in reducing pain in various neuropathic conditions and may be useful postoperatively. 4) Venlafaxine, another SNRI, which has shown effectiveness in neuropathic pain and could be considered for postoperative pain management.

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Duloxetine for Postoperative Pain After Knee Surgery

Phase 4

Recruiting

Research Sponsored by Rush University Medical Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age ≥ 18 years old

Any patient undergoing primary total knee arthroplasty for osteoarthritis

Must not have

Opioid tolerant patients defined as ≥ 60 morphine equivalents (MEQs) per day within 90 days prior to surgery

Known psychiatric disorder (specifically: generalized anxiety disorder, major depressive disorder, type I or type II bipolar disorder, and schizophrenia)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 months following surgery

Awards & highlights

Pivotal Trial

Drug Has Already Been Approved

Summary

This trial is testing if duloxetine can help reduce pain and opioid use in patients after knee replacement surgery. It focuses on patients who often have severe pain or heightened pain sensitivity. Duloxetine may work by altering brain chemicals to lessen pain signals. Duloxetine has been shown to have significant pain-relieving effects for managing chronic pain associated with conditions like fibromyalgia and diabetic peripheral neuropathic pain.

Who is the study for?

This trial is for adults under 80 years old who are having a knee replacement due to osteoarthritis and can speak English. They must be willing to follow the study plan and return for check-ups. People with severe health issues, mental disorders, heavy alcohol use, opioid tolerance, or kidney problems cannot join.

What is being tested?

The trial tests if duloxetine reduces pain and opioid need after knee surgery compared to a placebo (a pill without medicine). It also looks at how it affects patient-reported outcomes. Participants will be randomly assigned to either receive duloxetine or a placebo.

What are the potential side effects?

Duloxetine may cause nausea, dry mouth, sleepiness, constipation, fatigue and increased sweating. It might also affect mood and appetite. Not everyone will experience these side effects.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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I am having a knee replacement due to arthritis.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been taking at least 60 morphine equivalents daily for the last 3 months.

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I have been diagnosed with a psychiatric disorder like anxiety, depression, bipolar disorder, or schizophrenia.

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I do not drink more than 14 (if male) or 7 (if female) alcoholic beverages a week.

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I am over 80 years old.

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My health is severely limited by my illness.

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I have previously taken SSRIs or SNRIs.

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My kidney function is low, with a GFR under 30 mL/min or creatinine over 1.3 mg/dL.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 months following surgery

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 months following surgery

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 months following surgery for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Cumulative opioid consumption at post op day 14 (POD14)

Secondary study objectives

Complications

Patient reported outcome: Knee injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS,JR)

Patient reported outcome: Sleep duration and quality

+1 more

Side effects data

From 2012 Phase 4 trial • 291 Patients • NCT01118780

11%

Nausea

11%

Headache

Constipation

Dizziness

Dry mouth

Somnolence

Diarrhoea

Abdominal pain upper

Fall

Decreased appetite

Pruritus

Vertigo

Hyperhidrosis

Nasopharyngitis

Hypertensive crisis

Angina pectoris

Back pain

Insomnia

Large intestinal obstruction

100%

80%

60%

40%

20%

Study treatment Arm

Duloxetine

Placebo

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: DuloxetineExperimental Treatment1 Intervention

Patients randomized to the experimental arm of the study will receive 30 mg of duloxetine and will be advised to consume the medication orally (per os \[PO\]) daily starting one week prior to surgery and to continue until 6 weeks following surgery. The dose of 30 mg was selected as that has been used as that is the largest starting dose used in other RCTs without requiring a preceding adjustment period at a lower dosage.

Group II: ControlPlacebo Group1 Intervention

Patients randomized to the control arm will receive PO-matched placebo tablets and advised to consume their medication similar to the treatment arm. Both groups of patients will receive their medications from the pharmacy at Rush Medical Center, which will be responsible for providing patients with the appropriate regimen. All patients will receive the same postoperative multimodal analgesic regimen that is normally administered as part of conventional care to patients undergoing TKA at Rush University Medical Center.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Duloxetine

2011

Completed Phase 4

~4170

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Postoperative pain is commonly managed using a variety of pharmacologic treatments, including Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) like duloxetine. Duloxetine works by inhibiting the reuptake of serotonin and norepinephrine, which enhances the descending pain inhibitory pathways in the central nervous system, thereby reducing pain perception. This mechanism is particularly beneficial for postoperative pain patients as it not only alleviates pain but also addresses associated symptoms such as anxiety and depression, which can exacerbate pain experiences. Other treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, work by reducing inflammation and blocking pain signals, respectively. The multimodal approach, which may include SNRIs, is crucial for effective pain management, minimizing opioid use, and enhancing overall recovery.

The effect of duloxetine on mechanistic pain profiles, cognitive factors and clinical pain in patients with painful knee osteoarthritis-A randomized, double-blind, placebo-controlled, crossover study.