The Use of Venlafaxine in Reducing Pain in Primary Total Knee Replacement
Acute Pain · Chronic Pain · Knee Pain Chronic · Neuropathic Pain
What this study involves
The registry does not currently label this study as recruiting. Ask about its status before planning a screening visit.
- Study type
- Interventional
- Phase
- Phase 4
- Age range
- 18 years - 75 years
- Sex eligible
- All sexes
- Healthy volunteers
- Accepted
- Participants
- 100 Actual
These are starting points, not an eligibility decision. The research team must review the full requirements.
About the research
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 full 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.
Who may be able to participate?
The list below is the sponsor’s full registry wording. It can include conditions, prior treatment, test results and other requirements. A match in search does not mean you qualify.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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,
- prior knee surgery,
- BMI \> 40,
- bleeding disorders,
- history of recent falls,
- concurrent benzodiazepine use.
Treatment, groups and participation
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- Assignment
- Random assignment
- Masking
- Quadruple masked
Placebo
Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery.
Drug: Placebo
Venlafaxine
Subjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery.
Drug: Venlafaxine 37.5 MG
Venlafaxine 37.5 MG DRUG
venlafaxine 37.5mg daily for 7 consecutive days.
Placebo DRUG
placebo filled pill daily for 7 consecutive days.
What researchers are measuring
Outcome measures describe what is being studied. They are not proof that a treatment works.
Primary measures
Total Opioid Consumption on Postoperative Day 1
Time frame: Postoperative Day 1
Total opioid consumption measured in morphine milligram equivalents (MME) on postoperative day 1.
Secondary measures
NRS Pain Score at Postoperative Day 1
Time frame: Postoperative Day 1
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.
BPI Pain Interference Score at Postoperative Day 7
Time frame: Postoperative Day 7
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.
Pain Severity and Interference at 3 Months Post Operatively
Time frame: 3 months
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.
Opioid Consumption at 7 Days Postoperatively
Time frame: 7 days
morphine miligram equivalent
Functionality at 3 Months - KOOS Short Form
Time frame: 3 months
Knee Injury and Osteoarthritis Outcome Score Short Form (KOOS-12), a 12-item patient-reported questionnaire assessing knee-related quality of life. Scored 0-100 where 0 = extreme knee problems and 100 = no knee problems. Higher scores represent better knee function. Values reported as change from baseline to 3 months postoperatively (3-month score minus baseline score); higher change scores indicate greater improvement. Assessed at baseline and 3 months postoperatively.
Number of Participants Consuming Opioids at 3 Months
Time frame: 3 months
number of participants who reported consuming opioids at the 3-month follow-up.
Patient Satisfaction With Pain Control
Time frame: Postoperative Days 1, 2, 7, and 3 months
Patient satisfaction with pain control measured on a 0-100 visual analog scale, where 0 = completely dissatisfied and 100 = completely satisfied. Assessed at POD1, POD2, POD7, and 3 months postoperatively. Values represent model-predicted means from mixed-effects repeated measures analysis.
Functionality at 3 Months - PROMIS Global-10
Time frame: 3 months
PROMIS Global-10 (Patient-Reported Outcomes Measurement Information System), reported as T-scores standardized to the US general population (mean=50, SD=10). Four subscores reported separately: Global Mental Health (GMH), Global Physical Health (GPH), Mental Component Score (MCS), and Physical Component Score (PCS). For all subscores, higher T-scores represent better health outcomes. Values reported as change from baseline to 3 months postoperatively (3-month score minus baseline score); higher change scores indicate greater improvement. Assessed at baseline and 3 months postoperatively.
Review the complete result tables and limitations in the official record.
Open official results ↗Research locations (1)
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1 locations
University of California San FranciscoSan Francisco, California, United StatesStatus unknown
Study team and timeline
- Lead sponsor
- University of California, San Francisco
- Study start
- May 10, 2021 Actual
- Primary completion
- Feb 28, 2025 Actual
- Study completion
- Mar 31, 2025 Actual
- First posted
- Aug 26, 2021 Actual
- Last updated
- Nov 10, 2026 Actual
Official study contacts
No central contact is listed. Check the locations and the official record.
Official study title
The Use of Venlafaxine in Reducing Acute Post-Surgical Pain and Opioid Consumption in Primary Total Knee Replacement
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Source: ClinicalTrials.gov API v2. Information is submitted by sponsors and investigators. NLM does not approve the safety or science of all listed studies. Registry disclaimer.
Retrieved: Nov 12, 2026 · Last registry update: Nov 10, 2026