Acute PainPhase 4NCT05023278
The Use of Venlafaxine in Reducing Pain in Primary Total Knee Replacement
A Phase 4 study testing Venlafaxine 37.5 MG in people with Acute Pain and Chronic Pain, run by University of California, San Francisco at 1 site in United States.
Trial summary
Patients experience pain after their knee replacement surgery - and some may continue to experience persistent pain long after their knee replacement surgery. Traditional pain management strategies reply on pain medication such as opioids for pain control. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Pain, Chronic Pain, Knee Pain Chronic
- What is being tested?
- Venlafaxine 37.5 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 10 May 2021to 31 Mar 2025
- 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 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- adult (male and female) subjects aged 18 to 75,
- English speaking,
- are scheduled for primary total knee arthroplasty with planned spinal anesthesia with saphenous peripheral nerve block at the adductor canal.
Who cannot join
- general anesthesia,
- hepatic \& renal failure,
- history of diabetic peripheral neuropathic pain,
- chronic opioid use,
- concurrent use of antidepressants, triptans, and/or linezolid,
- allergy to the study medications,
Show all 11Show fewer
- prior knee surgery,
- BMI > 40,
- bleeding disorders,
- history of recent falls,
- concurrent benzodiazepine use.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: The Use of Venlafaxine in Reducing Acute Post-Surgical Pain and Opioid Consumption in Primary Total Knee Replacement
Patients experience pain after their knee replacement surgery - and some may continue to experience persistent pain long after their knee replacement surgery. Traditional pain management strategies reply on pain medication such as opioids for pain control. However, these drugs do not work well for pain associated with movement or the the nerve pain (tingling, electrical sensations) after surgery. In addition, opioids are associated with significant side effects such as nausea, vomiting, respiratory depression, depression, cognitive dysfunction and risk of persistent opioid use. Neuropathic pain medications, such as venlafaxine are effective in managing nerve pain. Recent studies also support its potential role in acute pain management. Here, we propose a prospective randomized clinical trial 1) to evaluate the efficacy of Venlafaxine in reducing pain intensity and opioid consumption at post-operative day 1 (POD1) and 1- week after surgery, and 2) to examine whether the use of Venlafaxine will reduce the incidents of chronic postsurgical pain in TKA patients at 3-month time point.
Read the detailed description
Patients meeting the inclusion criteria will be randomized to receive either Venlafaxine extended release (ER) 37.5 mg/d or a placebo on the day of surgery and continue the treatment for 7 days after surgery. The primary outcomes include pain severity score (numeric rating scale, NRS) and consumption of morphine miligram equivalent (MME) at 24 hours. The secondary outcome will measure MME and NRS at postoperative day 7. In addition, the disability scale and perceived function 3 months after surgery will be compared to the baseline level by using PROMIS (Patient-Reported Outcomes Measurement Information System)10 Global Health, KOOS, JR. (Knee injury and Osteoarthritis Outcome Score Short Form), and VR-12 (Veterans RAND 12 Item Health Survey) Scale.
- Conditions
- Acute Pain, Chronic Pain, Knee Pain Chronic, Neuropathic Pain
- Being tested
- Venlafaxine 37.5 MG, Placebo
- Medical subject headings
- Acute Pain, Chronic Pain, Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Venlafaxine 37.5 MGDrug
Also called SNRI analgesia
venlafaxine 37.5mg daily for 7 consecutive days.
PlaceboDrug
Also called control
placebo filled pill daily for 7 consecutive days.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery. Receives: Drug: Placebo |
| Venlafaxine | Experimental | Subjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery. Receives: Drug: Venlafaxine 37.5 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative 24 hour total opioid consumption
morphine miligram equivalent
Measured: 24 hours
Secondary outcomes (9)
Pain numeric rating scale at 24 hours post operatively
Pain Scores will be measured on the Numerical Rating Scale (NRS), the score ranges from 0-10, zero indicating no pain and 10 indicating the worst pain.
Measured: 24 hours
Pain severity and interference at 7 days post operatively
The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.The BPI scale defines pain as follows:1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain.
Measured: 7 days
Pain severity and interference at 3 months post operatively
The Brief Pain Inventory (BPI) assesses the severity of pain and its impact on functioning.The BPI scale defines pain as follows:1 - 4 = Mild Pain. Worst Pain Score: 5 - 6 = Moderate Pain. Worst Pain Score: 7 - 10 = Severe Pain.
Measured: 3 months
Functionality at 7 days postoperatively
Knee injury and osteoarthritis outcome score short form: Patient-Reported Outcomes Measurement Information System (PROMIS), item health survey. The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The average Score is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.
Measured: 7 days
Functionality at 7 days postoperatively
Knee injury and osteoarthritis outcome score short form, veterans RAND 12 (VR12) item health survey. The results of the VR-12 are summarized as two scores - a Mental Component Score (MCS) and a Physical Component Score (PCS). The United States population average PCS and MCS are both 50 points. The United States population standard deviation is 10 points. Therefore, each increment of 10 points above or below 50 corresponds to one standard deviation away from the population average.
Measured: 7 days
Functionality at 3 months postoperatively
Knee injury and osteoarthritis outcome score short form: Patient-Reported Outcomes Measurement Information System (PROMIS), item health survey. The PROMIS Global-10 is a 10-item patient-reported questionnaire in which the response options are presented as 5-point (as well as a single 11-point) rating scales. The average Score is 50 points, with a standard deviation of 10 points. Higher scores indicate a healthier patient.
Measured: 3 months
Functionality at 3 months postoperatively
Knee injury and osteoarthritis outcome score short form, veterans RAND 12 (VR12) item health survey. The results of the VR-12 are summarized as two scores - a Mental Component Score (MCS) and a Physical Component Score (PCS). The United States population average PCS and MCS are both 50 points. The United States population standard deviation is 10 points. Therefore, each increment of 10 points above or below 50 corresponds to one standard deviation away from the population average.
Measured: 3 months
Opioid consumption at 7 days postoperatively
morphine miligram equivalent
Measured: 7 days
Opioid consumption at 3 months postoperatively
morphine miligram equivalent
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2021
- Study start10 May 2021
- Primary completion28 Feb 2025
- Study completion31 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute PainStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Orthopedic Research and Education Foundation
- Responsible party
- Sponsor
- Investigators
- Matthias Behrends, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05023278
- Sponsor's protocol ID
- 20-32595
- Status last verified
- May 2025
- First submitted
- 19 Jul 2021
- Last updated
- 20 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: We will share our raw clinical data with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Use of Venlafaxine in Reducing Acute Post-Surgical Pain and Opioid Consumption in Primary Total Knee Replacement
- ClinicalTrials.gov ID
- NCT05023278
- Acronym / sponsor ID
- 20-32595
- Conditions
- Acute Pain, Chronic Pain, Knee Pain Chronic, Neuropathic Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Orthopedic Research and Education Foundation
- Study start
- 10 May 2021 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 31 Mar 2025 (actual)
- First posted
- 26 Aug 2021 (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.
Patients experience pain after their knee replacement surgery - and some may continue to experience persistent pain long after their knee replacement surgery. Traditional pain management strategies reply on pain medication such as opioids for pain control. However, these drugs do not work well for pain associated with movement or the the nerve pain (tingling, electrical sensations) after surgery. In addition, opioids are associated with significant side effects such as nausea, vomiting, respiratory depression, depression, cognitive dysfunction and risk of persistent opioid use. Neuropathic pain medications, such as venlafaxine are effective in managing nerve pain. Recent studies also support its potential role in acute pain management. Here, we propose a prospective randomized clinical trial 1) to evaluate the efficacy of Venlafaxine in reducing pain intensity and opioid consumption at post-operative day 1 (POD1) and 1- week after surgery, and 2) to examine whether the use of Venlafaxine will reduce the incidents of chronic postsurgical pain in TKA patients at 3-month time point.
Detailed description
Patients meeting the inclusion criteria will be randomized to receive either Venlafaxine extended release (ER) 37.5 mg/d or a placebo on the day of surgery and continue the treatment for 7 days after surgery. The primary outcomes include pain severity score (numeric rating scale, NRS) and consumption of morphine miligram equivalent (MME) at 24 hours. The secondary outcome will measure MME and NRS at postoperative day 7. In addition, the disability scale and perceived function 3 months after surgery will be compared to the baseline level by using PROMIS (Patient-Reported Outcomes Measurement Information System)10 Global Health, KOOS, JR. (Knee injury and Osteoarthritis Outcome Score Short Form), and VR-12 (Veterans RAND 12 Item Health Survey) Scale.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboSubjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery. |
| Venlafaxine | Experimental | Drug: Venlafaxine 37.5 MGSubjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- adult (male and female) subjects aged 18 to 75,
- English speaking,
- are scheduled for primary total knee arthroplasty with planned spinal anesthesia with saphenous peripheral nerve block at the adductor canal.
Key exclusion criteria (11 listed)
- general anesthesia,
- hepatic \& renal failure,
- history of diabetic peripheral neuropathic pain,
- chronic opioid use,
- concurrent use of antidepressants, triptans, and/or linezolid,
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 |
|---|---|---|
| Venlafaxine 37.5 MGAlso: SNRI analgesiavenlafaxine 37.5mg daily for 7 consecutive days. | Drug | Venlafaxine |
| PlaceboAlso: controlplacebo filled pill daily for 7 consecutive days. | Drug | Placebo |
Primary outcome
Cumulative 24 hour total opioid consumption
Time frame: 24 hours
morphine miligram equivalent
9 secondary outcomes
Pain numeric rating scale at 24 hours post operatively
Time frame: 24 hours
Pain severity and interference at 7 days post operatively
Time frame: 7 days
Pain severity and interference at 3 months post operatively
Time frame: 3 months
Functionality at 7 days postoperatively
Time frame: 7 days
Functionality at 7 days postoperatively
Time frame: 7 days
Functionality at 3 months postoperatively
Time frame: 3 months
Functionality at 3 months postoperatively
Time frame: 3 months
Opioid consumption at 7 days postoperatively
Time frame: 7 days
Opioid consumption at 3 months postoperatively
Time frame: 3 months
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 20 May 2025.
- Individual participant dataSharing planned: Yes. We will share our raw clinical data with other researchers.
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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.
Matthias Behrends, MD principal investigator
University of California, San Francisco
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 Venlafaxine 37.5 MG in people with Acute Pain and Chronic Pain, run by University of California, San Francisco 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 11 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 20 May 2025. 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?
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?
Cumulative 24 hour total opioid consumption (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 20 May 2025.