Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: University of California, San Francisco
Prior Safety Data
Approved in 3 jurisdictions
Trial Summary
What is the purpose of this trial?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.
What data supports the idea that Venlafaxine for Knee Pain is an effective treatment?The available research does not provide any data or studies on the effectiveness of Venlafaxine for treating knee pain. The articles focus on other treatments and conditions, such as cancer-related therapies and osteonecrosis of the jaw, but do not mention Venlafaxine or its use for knee pain.1011121314
Do I need to stop my current medications to join the trial?Yes, you must stop taking antidepressants, triptans, linezolid, and benzodiazepines to join the trial.
What safety data exists for venlafaxine?Venlafaxine has been shown to be safe and well-tolerated in clinical trials involving patients with major depression. In studies involving 3,082 patients, common side effects included nausea, headache, insomnia, somnolence, dry mouth, dizziness, constipation, asthenia, sweating, and nervousness. Serious adverse events were rare, and venlafaxine was found to have a safety profile comparable to third-generation antidepressants. A small percentage of patients experienced modest increases in blood pressure. Tolerability and safety in elderly patients were similar to those in younger patients. In cases of overdose, patients recovered without sequelae.12367
Is the drug Venlafaxine a promising treatment for knee pain?Yes, Venlafaxine shows promise as a treatment for pain. It has been effective in reducing pain in various studies, including relieving pain in rats and managing pain in patients with different conditions. It also helps with pain related to nerve damage and inflammation.34589
Eligibility Criteria
This trial is for English-speaking adults aged 18 to 75 who are scheduled for primary total knee replacement surgery with specific anesthesia. It's not for those on antidepressants, triptans, or linezolid; with allergies to study meds; BMI over 40; prior knee surgery; recent falls; liver/renal failure; bleeding disorders; general anesthesia use; diabetic nerve pain history or chronic opioid/benzodiazepine users.Inclusion Criteria
I am between 18 and 75 years old.
I am scheduled for a knee replacement surgery with specific anesthesia and nerve block.
Exclusion Criteria
I have a bleeding disorder.
I do not have liver or kidney failure.
I have experienced nerve pain due to diabetes.
I have fallen recently.
I will undergo surgery with general anesthesia.
I am currently taking benzodiazepines.
I am currently taking antidepressants, triptans, or linezolid.
I have had knee surgery before.
Participant Groups
The trial tests if Venlafaxine (37.5 MG) can reduce pain and opioid use after knee replacement compared to a placebo. The focus is on the first day post-op and one week later, plus checking if it lowers long-term chronic pain at three months.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: VenlafaxineExperimental Treatment1 Intervention
Subjects in venlafaxine arm will receive venlafaxine 37.5mg daily for 7 consecutive days starting on day of primary arthroplasty surgery.
Group II: PlaceboPlacebo Group1 Intervention
Subjects in placebo arm will receive inactive placebo capsule daily for 7 consecutive days starting on day of primary arthroplasty surgery.
Venlafaxine is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Efexor for:
- Major depressive disorder
- Generalized anxiety disorder
- Social anxiety disorder
- Panic disorder
🇺🇸 Approved in United States as Effexor for:
- Major depressive disorder
- Generalized anxiety disorder
- Social anxiety disorder
- Panic disorder
🇨🇦 Approved in Canada as Effexor for:
- Major depressive disorder
- Generalized anxiety disorder
- Social anxiety disorder
- Panic disorder
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of California San FranciscoSan Francisco, CA
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Who is running the clinical trial?
University of California, San FranciscoLead Sponsor
Orthopedic Research and Education FoundationCollaborator
References
Safety and tolerance profile of venlafaxine. [2019]Venlafaxine has been shown in clinical trials to be safe and well tolerated in patients with major depression. Data were pooled from 19 studies in which 2181 patients were given venlafaxine, 451 were given placebo and 591 were given a reference antidepressant (imipramine, trazodone, clomipramine, maprotiline, dothiepin or amineptine). Long-term safety was evaluated in 422 patients who were given venlafaxine for at least 1 year; as well, a total of 229 elderly patients have been treated with venlafaxine, including 66 who were given it for at least 1 year. The adverse events that occurred during short-term treatment in > or = 10% of patients were nausea, headache, insomnia, somnolence, dry mouth, dizziness, constipation, asthenia, sweating and nervousness. In comparator-controlled trials, the frequency of anticholinergic events with the reference agents was approximately twice that with venlafaxine. The safety profile and patient acceptability of venlafaxine are comparable to those of third-generation antidepressants, and possibly better than those of first-generation agents.
The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. [2022]The tolerability and safety of venlafaxine hydrochloride, a new serotonin and norepinephrine reuptake inhibitor, are reviewed in this article. The data presented here are based on a pool of 3,082 patients who were treated with this agent during clinical trials. Of these patients, 2,897 received venlafaxine for depression; 455 of these patients were treated for more than 360 days. The tolerability and safety profiles of venlafaxine were similar to those previously reported for selective serotonin reuptake inhibitors. Patients receiving venlafaxine experienced nausea, insomnia, dizziness, somnolence, constipation, and sweating more often than did patients receiving placebo but reported anticholinergic events less frequently than did patients receiving tricyclics. This is accounted for by the fact that, unlike the tricyclics, venlafaxine lacks significant affinity for muscarinic cholinergic receptors. Resolution of venlafaxine-associated nausea occurred rapidly in the vast majority of the patients who reported it at the start of therapy. Serious adverse events were rare among venlafaxine-treated patients. A small percentage of the patients given venlafaxine experienced modest but significant increases in blood-pressure readings, similar to those observed among imipramine-treated patients. At mean daily venlafaxine dosages of up to 300 mg, the percentage of venlafaxine-treated patients who had sustained elevations in supine diastolic blood pressure during treatment ranged from 2% to 6%, compared with 2% and 5% among the placebo- and imipramine-treated patients, respectively. All of the 14 patients who took an overdose of venlafaxine recovered without sequelae. Tolerability and safety in the elderly did not differ significantly from that observed in younger patients.
Venlafaxine hydrochloride (Effexor) relieves thermal hyperalgesia in rats with an experimental mononeuropathy. [2022]Venlafaxine hydrochloride (Effexor) is a structurally novel antidepressant that inhibits reuptake of 5-hydroxytryptamine and noradrenaline, but unlike the older antidepressants, has few side-effects. The objective of this study was to determine whether venlafaxine relieves thermal hyperalgesia in rats with neuropathic pain due to chronic constriction injury (CCI) of the sciatic nerve. Paw withdrawal latency (PWL) to heat was tested for each hind paw. A painful neuropathy was induced in 24 male Sprague-Dawley rats (Group 1) as described by Bennett and Xie. Rats randomly received either oral venlafaxine (22 mg/kg) or placebo via gavage feeding beginning the day after surgery. Postoperative PWL testing began 3 days after CCI (Time 0). A second group of 12 rats (Group 2) was used to confirm that venlafaxine reverses hyperalgesia in rats with a fully developed neuropathic lesion. These animals began to receive oral venlafaxine (22 mg/kg) starting on the third postoperative day, after the presence of thermal hyperalgesia was verified through PWL testing. Testing was continued for 5 days, during venlafaxine administration. A third group of 12 rats (Group 3) had activity measured before and after treatment with venlafaxine (22 mg/kg). Rats in the placebo group developed thermal hyperalgesia while those that received venlafaxine did not. Venlafaxine also appeared to have a mild non-specific analgesic effect that increased PWL in the sham limb. In Group 2, thermal hyperalgesia was present on day 3, but following treatment with venlafaxine, thermal hyperalgesia resolved. Activity measurements confirmed that venlafaxine was not sedating in this rat model.
Venlafaxine-tramadol similarities. [2019]Venlafaxine and tramadol are relatively new compounds indicated for the treatment of depression and pain, respectively. These agents share a number of molecular and pharmacological features that may allow for broader and overlapping therapeutic indications for both drugs. Additionally, certain patient populations with coexisting depression and pain syndromes could potentially be treated with a single agent.
Protection against oxaliplatin acute neurosensory toxicity by venlafaxine. [2019]Venlafaxine (Effexor; Wyeth Lederlé) has previously shown therapeutic effects for the management of chronic and neuropathic pains. We report here the efficacy of venlafaxine upon acute neurosensory symptoms secondary to oxaliplatin toxicity. A dose of 50 mg of venlafaxine was given orally at the beginning of the oxaliplatin infusion. Patients did not experience any or very low paresthesias, even in the cold. As the results were very dramatic and reproducible, we propose that venlafaxine may be of use in the daily management of oxaliplatin-related neurosensory toxicity.
Efficacy of venlafaxine for the long term treatment of chronic pain with associated major depressive disorder. [2022]This was an open-label, single-center study of the long-term efficacy and effectiveness of venlafaxine extended release (XR) in the treatment of chronic pain and depression in outpatients. All patients have been diagnosed with major depressive disorder (MDD) of various types, with or without chronic pain, and had previously failed treatment with either tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs).
Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study. [2022]To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions-Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P
Evaluation of antinociceptive and anti-inflammatory effects of venlafaxine in the rat. [2022]The aim of this study was to test antinociceptive properties of venlafaxine in rats with carrageenan-induced pain and inflammation. Pain was provoked with carrageenan (1%) injection into the plantar surface of the rat paw-pad. The effect of venlafaxine on carrageenan-induced mechanical hypersensitivity, mechanical stimulation response (the von Frey monofilament test) as well as the size of carrageenan-induced paw edema were tested at 2 to 24 hours following the toxin injection into the rat paw-pad. Pretreatment with venlafaxine significantly reduced or completely abolished the enhanced sensitivity to mechanical stimuli provoked by peripheral carrageenan injection. The study demonstrated the efficacy of peripherally applied venlafaxine pretreatment on the pain component of inflammatory process.
[Results of a study of velaxin (venlafaxine) efficacy in patients with subacute and chronic spondylogenic dorsalgia]. [2022]An open comparative study of efficacy and tolerability of velaxin (venlafaxine with prolonged action), which has been prescribed in a single dosage of 75 mg daily during 8 weeks, included 47 patients with subacute and chronic spondylogenic dorsopathy (SD). Degree of pain chronisation and its intensity (The Visual Analogous Scale - VAS and the Verbal Pain Scale - VPS) and levels of daily activity restriction (the modified Pain Disability Questionnaire - PDQ), anxiety and depression were measured. The comparison group consisted of 32 patients with SD matched for clinical characteristics with the main group, who did not receive antidepressants and antiepileptics in the complex treatment of pain syndrome. Scores of VAS, VPS and PDQ in the main group were 69+/-2.9; 2.8+/-0.1 and 44.2+/-3.2 respectively, at baseline; 38.8+/-3.3 (p
Aflibercept for metastatic colorectal cancer: safety data from the Spanish named patient program. [2015]Aflibercept increased overall survival with acceptable tolerability in metastatic colorectal cancer (mCRC) when it was used in combination with FOLFIRI after progression on a first-line oxaliplatin regimen (VELOUR study). The safety profile of aflibercept in day-to-day clinical practice was assessed.
Jaw osteonecrosis associated with aflibercept, irinotecan and fluorouracil: attention to oral district. [2022]The antiangiogenic monoclonal antibody aflibercept in association with fluorouracil and irinotecan improves the survival of patients with metastatic colorectal cancer (mCRC) treated previously with oxaliplatin-based therapy. Multiple reports raised the hypothesis that the concomitant use of antiresorptive drugs and antiangiogenic drugs may increase the risk of osteonecrosis of the jaw (ONJ). Some reports have been published regarding cases of ONJ during treatment with bevacizumab for mCRC.
Pentoxifylline and tocopherol in the management of cancer patients with medication-related osteonecrosis of the jaw: an observational retrospective study of initial case series. [2018]Very few studies have evaluated the efficacy of pentoxifylline and tocopherol (PENT-E) in the management of medication-related osteonecrosis of the jaw (MRONJ), although some studies have shown the therapeutic and prophylactic benefit of PENT-E in the management of osteoradionecrosis. We report the outcomes of MRONJ managed with PENT-E in patients with metastatic bone disease or multiple myeloma.
Impact of Prior Bevacizumab Treatment on VEGF-A and PlGF Levels and Outcome Following Second-Line Aflibercept Treatment: Biomarker Post Hoc Analysis of the VELOUR Trial. [2020]Label="PURPOSE">Aflibercept is a targeted anti-VEGF therapy used to treat patients with metastatic colorectal cancer (mCRC) following progression on oxaliplatin-based regimens. This post hoc study evaluated the effect of prior bevacizumab treatment and growth factor levels on patient outcomes associated with aflibercept in the VELOUR phase III trial.
Patients' quality of life improves after surgical intervention of stage III medication-related osteonecrosis of the jaw. [2022]The treatment of advanced stages of medication-related osteonecrosis of the jaw (MRONJ) remains challenging. In order to improve decision making concerning the therapy, we examined the change of patients' quality of life (QoL) after surgical treatment of MRONJ stage III.