Phenol Neurolysis of Genicular Nerves for Chronic Knee Pain

Phenol Neurolysis of Genicular Nerves for Chronic Knee Pain Following Total Knee Arthroplasty: a Pilot Prospective, Randomized, Crossover Trial

Chronic knee pain from osteoarthritis (OA) is commonly treated with total knee arthroplasty (TKA) when conservative therapies fail to provide pain relief. More than 600,000 TKAs are performed in the U.S. annually, a number that continues to increase. A logistic-regression model suggests that the incidence rate of TKA will increase by 143% in the United States by 2050 compared to 2012. Although TKA is successful in reducing knee pain and joint stiffness in most cases, it can be associated with a 7-35% incidence of persistent refractory post-surgical knee pain.

Aim:

To determine whether chemical neurolysis of the genicular nerves with 6% aqueous phenol is non-inferior in reducing knee pain as compared to corticosteroid injection of the genicular nerves, in patients with refractory chronic knee pain for more than 6 months after total knee replacement.

Hypothesis:

Chemical neurolysis of genicular nerves with phenol will provide equal or superior pain relief than corticosteroid genicular nerve injections at 3 months, as measured by the Oxford Knee Score.

Study Overview

• Status: Withdrawn
• Conditions: Pain, Chronic
• Intervention / Treatment: Drug: Phenol Injection; Drug: Methylprednisolone Injection

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 91 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ages 40-95 years
• Patients with knee pain, on average > 4 (NRS) persisting more than 6 months after TKA
• Willingness to undergo image guided diagnostic nerve block and the study intervention

Exclusion Criteria:

• Pain score (NRS) < 4 at time of study enrollment
• Conditions that preclude the diagnostic block or the study intervention (e.g., irreversible coagulopathy or bleeding disorder, allergic reaction/contraindication to local anesthetic, contrast dye, steroids, and/or phenol, pregnancy, severe or uncontrolled medical illness).
• Evidence of indolent infection of the knee prosthesis (elevated C-reactive protein assessed when clinically indicated)
• Inability to write, speak, or read in English
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group: Phenol injection; 6% aqueous phenol 2.5 mL will be mixed with 0.5 mL iopamidol 300 and will be injected at each target sites	Drug: Phenol Injection; 6% aqueous phenol 2.5 mL will be mixed with 0.5 mL iopamidol 300 and will be injected at each target site with live, pulsed fluoroscopy (5-8 seconds at each location) to observe the contrast dye-tagged phenol covering the lateral margin of the femur or tibia respectively on AP and lateral views. The needles will then be removed and band-aids placed.; Other Names: Phenol
Other: Control Group: Methylprednisolone injection; Methylprednisolone acetate 10 mg with 2 mL preservative free saline and 0.5 mL iopamidol 300 will be injected at each of the target site	Drug: Methylprednisolone Injection; Methylprednisolone acetate 10 mg with 2 mL preservative saline and 0.5 mL iopamidol 300 will be injected at each of the 3 target sites with live, pulsed fluoroscopy (5-8 seconds at each location) to observe the contrast dye-tagged steroid mixture covering the lateral margin of the femur or tibia respectively on AP and lateral views; the needles will be removed and band-aids placed.; Other Names: Methylprednisolone acetate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxford Knee Score	Oxford Knee Score is a tool which measures 6 post operative items (pain,flexion contracture, extension lag, total range of flexion, alignment of varus and valgus,stability (antero-posterior and mediolateral). The scoring is: below 60 is poor, scoring 60-69 fair, scoring 70-79 good, 80-100 excellent.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Rating Scale Score	The proportion of subjects who have > 50% reduction in pain based on the Numeric Rating Scale at 3 months. The NRS is a scale of 0 (no pain) to 10 (worst pain imaginable)	3months
Numeric Rating Scale Score	The proportion of subjects who have > 50% reduction in pain based on the Numeric Rating Scale at 6 months. The NRS is a scale of 0 (no pain) to 10 (worst pain imaginable)	6 months
Patients Global Impression of Change	Patients Global Impression of Change (GPIC) is a scale of 0 (much better) to 10 (much worse)	3 Months
Patients Global Impression of Change	Patients Global Impression of Change (GPIC) is a scale of 0 (much better) to 10 (much worse)	6 Months
Opioid analgesic use at 3 months	Opioid analgesic daily use by self reporting .	3 months
Opioid analgesic use at 6 months	Opioid analgesic daily use by self reporting.	6 months
Non-opioid analgesic use at 3 months	Non opioid analgesic daily use by self reporting.	3 Months
Non-opioid analgesic use at 6 months	Non opioid analgesic daily use by self reporting.	6 Months
PROMIS Pain Intensity Short Form 3a	3 question pain survey. 5 responses (had no pain),(mild), (moderate), (severe) and (very severe)	Baseline
PROMIS Pain Intensity Short Form 3a	3 question pain survey. 5 responses (had no pain),(mild), (moderate), (severe) and (very severe)	3 Months
PROMIS Pain Intensity Short Form 3a	3 question pain survey. 5 responses (had no pain),(mild), (moderate), (severe) and (very severe)	6 Months
PROMIS Sleep Disturbance Short Form 4a	4 question sleep survey. First section is quality of sleep rated on a 5 response (very poor)- (very good) scale.Section rating quality of sleep based on 5 response choices (not at all) to (very much)	Baseline
PROMIS Sleep Disturbance Short Form 4a	4 question sleep survey. First section is quality of sleep rated on a 5 response (very poor)- (very good) scale.Section rating quality of sleep based on 5 response choices (not at all) to (very much)	3 Months
PROMIS Sleep Disturbance Short Form 4a	4 question sleep survey. First section is quality of sleep rated on a 5 response (very poor)- (very good) scale.Section rating quality of sleep based on 5 response choices (not at all) to (very much)	6 Months
PROMIS Pain Interference Short Form 6b	6 question pain survey. First section is interference of pain rated on a 5 response (not at all)- (very much) scale. Section is one socialization question with 5 response choices (never)- (always)	Baseline
PROMIS Pain Interference Short Form 6b	6 question pain survey. First section is interference of pain rated on a 5 response (not at all)- (very much) scale. Section is one socialization question with 5 response choices (never)- (always)	3 Months
PROMIS Pain Interference Short Form 6b	6 question pain survey. First section is interference of pain rated on a 5 response (not at all)- (very much) scale. Section is one socialization question with 5 response choices (never)- (always)	6 Months
Oxford Knee Score	12 question survey with 5 choice responses based on severity of pain while accomplishing activities of daily living.	Baseline
Oxford Knee Score	12 question survey with 5 choice responses based on severity of pain while accomplishing activities of daily living.	6 Months
Hospital Anxiety and Depression Scale	Hospital Anxiety and Depression Scale (HADS) is a 14 question survey (7 anxiety and 7 depression) questions answered on a 0 (low) - 3 (high) scale.Total score of 0-7 is normal, 8-10 is baseline abnormal and a score between 11-21 is abnormal.	Baseline
Hospital Anxiety and Depression Scale	Hospital Anxiety and Depression Scale (HADS) is a 14 question survey (7 anxiety and 7 depression) questions answered on a 0 (low) - 3 (high) scale.Total score of 0-7 is normal, 8-10 is baseline abnormal and a score between 11-21 is abnormal.	3 Month
Hospital Anxiety and Depression Scale	Hospital Anxiety and Depression Scale (HADS) is a 14 question survey (7 anxiety and 7 depression) questions answered on a 0 (low) - 3 (high) scale. Total score of 0-7 is normal, 8-10 is baseline abnormal and a score between 11-21 is abnormal.	6 Month

Collaborators and Investigators

• Sponsor: Northwestern University
• Investigators: Principal Investigator: David Walega, MD, Northwestern University

Publications and helpful links

General Publications

• Lewis GN, Rice DA, McNair PJ, Kluger M. Predictors of persistent pain after total knee arthroplasty: a systematic review and meta-analysis. Br J Anaesth. 2015 Apr;114(4):551-61. doi: 10.1093/bja/aeu441. Epub 2014 Dec 26.
• Puolakka PA, Rorarius MG, Roviola M, Puolakka TJ, Nordhausen K, Lindgren L. Persistent pain following knee arthroplasty. Eur J Anaesthesiol. 2010 May;27(5):455-60. doi: 10.1097/EJA.0b013e328335b31c.
• Protzman NM, Gyi J, Malhotra AD, Kooch JE. Examining the feasibility of radiofrequency treatment for chronic knee pain after total knee arthroplasty. PM R. 2014 Apr;6(4):373-6. doi: 10.1016/j.pmrj.2013.10.003. Epub 2013 Dec 27.
• Fischer HB, Simanski CJ, Sharp C, Bonnet F, Camu F, Neugebauer EA, Rawal N, Joshi GP, Schug SA, Kehlet H; PROSPECT Working Group. A procedure-specific systematic review and consensus recommendations for postoperative analgesia following total knee arthroplasty. Anaesthesia. 2008 Oct;63(10):1105-23. doi: 10.1111/j.1365-2044.2008.05565.x. Epub 2008 Jul 10.
• Nguyen US, Zhang Y, Zhu Y, Niu J, Zhang B, Felson DT. Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey and cohort data. Ann Intern Med. 2011 Dec 6;155(11):725-32. doi: 10.7326/0003-4819-155-11-201112060-00004.
• Buvanendran A, Fiala J, Patel KA, Golden AD, Moric M, Kroin JS. The Incidence and Severity of Postoperative Pain following Inpatient Surgery. Pain Med. 2015 Dec;16(12):2277-83. doi: 10.1111/pme.12751. Epub 2015 Apr 27.
• Drosos GI, Triantafilidou T, Ververidis A, Agelopoulou C, Vogiatzaki T, Kazakos K. Persistent post-surgical pain and neuropathic pain after total knee replacement. World J Orthop. 2015 Aug 18;6(7):528-36. doi: 10.5312/wjo.v6.i7.528. eCollection 2015 Aug 18.
• Inacio MCS, Paxton EW, Graves SE, Namba RS, Nemes S. Projected increase in total knee arthroplasty in the United States - an alternative projection model. Osteoarthritis Cartilage. 2017 Nov;25(11):1797-1803. doi: 10.1016/j.joca.2017.07.022. Epub 2017 Aug 8.
• Sylvester LN, Goree JH. Genicular Radiofrequency Ablation for Treatment of Post Total Knee Arthroplasty Posterior Thigh Pain: A Case Report. A A Case Rep. 2017 Nov 15;9(10):292-293. doi: 10.1213/XAA.0000000000000596.
• Qudsi-Sinclair S, Borras-Rubio E, Abellan-Guillen JF, Padilla Del Rey ML, Ruiz-Merino G. A Comparison of Genicular Nerve Treatment Using Either Radiofrequency or Analgesic Block with Corticosteroid for Pain after a Total Knee Arthroplasty: A Double-Blind, Randomized Clinical Study. Pain Pract. 2017 Jun;17(5):578-588. doi: 10.1111/papr.12481. Epub 2016 Sep 19.
• Walega DR, McCormick ZL. Chemical Neurolysis of the Genicular Nerves for Chronic Knee Pain: Reviving an Old Dog and an Old Trick. Pain Med. 2018 Sep 1;19(9):1882-1884. doi: 10.1093/pm/pny023. No abstract available.
• Koyyalagunta D, Engle MP, Yu J, Feng L, Novy DM. The Effectiveness of Alcohol Versus Phenol Based Splanchnic Nerve Neurolysis for the Treatment of Intra-Abdominal Cancer Pain. Pain Physician. 2016 May;19(4):281-92.
• Wang PJ, Shang MY, Qian Z, Shao CW, Wang JH, Zhao XH. CT-guided percutaneous neurolytic celiac plexus block technique. Abdom Imaging. 2006 Nov-Dec;31(6):710-8. doi: 10.1007/s00261-006-9153-5.
• Kirazli Y, On AY, Kismali B, Aksit R. Comparison of phenol block and botulinus toxin type A in the treatment of spastic foot after stroke: a randomized, double-blind trial. Am J Phys Med Rehabil. 1998 Nov-Dec;77(6):510-5. doi: 10.1097/00002060-199811000-00012.
• Ahmed A, Arora D, Kochhar AK. Ultrasound-guided alcohol neurolysis of lateral femoral cutaneous nerve for intractable meralgia paresthetica: a case series. Br J Pain. 2016 Nov;10(4):232-237. doi: 10.1177/2049463716668811. Epub 2016 Sep 16.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2019
• Primary Completion (Anticipated): July 1, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: June 3, 2019
• First Posted (Actual): June 4, 2019

Study Record Updates

• Last Update Posted (Actual): April 28, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Chronic Pain; Total knee arthroplasty
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Pharmaceutical Solutions; Disinfectants; Sclerosing Solutions; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Phenol
• Other Study ID Numbers: STU00209591

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No