Perioperative Colchicine for TKA

NCT06936709 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 2024-0488
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is a prospective, randomized, double-blinded, placebo-controlled study of the drug colchicine in the acute postoperative period for patients who are undergoing a total knee arthroplasty (TKA). Patients aged 18 years or older who are undergoing TKA will be invited to participate in the study. The primary endpoint of this study is to determine if colchicine, an anti-inflammatory medication commonly used for gout attacks, will decrease the postoperative pain of patients undergoing elective TKA.

Conditions

Osteoarthritis of Knee; Recovery Following Primary Total Knee Arthroplasty; Perioperative Pain Control

Keywords

Total Knee Arthroplasty; Colchicine; Postoperative Pain

Outcome Measures

Primary Outcomes (1)

• Postoperative VAS pain score

  Subjects will receive a post-operative pain journal upon hospital discharge on postoperative day 0. The journal will include three time points (morning, midday, and bedtime) in which they will record a VAS pain score ranging from 0-10 for post-operative days 1-3. 0 being no pain, 10 being the worst pain they have ever experienced.

  From postoperative day 0 through postoperative day 4.

Secondary Outcomes (5)

• Daily Opioid Usage

  From postoperative day 0 through postoperative day 3.

• Postoperative KOOS-JR Score

  From postoperative day 0 through postoperative week 12.

• Postoperative Knee Flexion

  Postoperative day 0 through postoperative week 12.

• 90 day postoperative complications

  Postoperative day 0 to postoperative day 90

• Colchicine Related Side Effects

  Postoperative day 0 through postoperative day 3.

Study Arms (3)

Colchicine Loading Dose Only

EXPERIMENTAL

Patients in this arm will receive 1.8 mg of colchicine on postoperative day 0. This dosage aligns with standard of care loading dose for acute gout attacks. This will be a one time dosage of colchicine. On postoperative days 1-3, patients will take placebo dextrose pills twice daily.

Drug: Colchicine 1.8 mg (loading dose) + Dextrose Oral Placebo

Colchicine Loading Dose + Maintenance Dose

EXPERIMENTAL

Patients in this arm will receive a 1.8 mg loading dose of colchicine on postoperative day 0. They will then take a 0.6 mg maintenance dose twice daily on postoperative days 1-3. This dosage of colchicine in this arm models standard of care dosing for acute gout attacks.

Drug: Colchicine 1.8 mg + 0.6 mg

Placebo Group

PLACEBO COMPARATOR

Patients in this arm will receive a placebo dextrose pill on postoperative day 0. They will then take a placebo dextrose pill twice daily on postoperative days 1-3.

Drug: Dextrose Oral Placebo

Interventions

Colchicine 1.8 mg (loading dose) + Dextrose Oral Placebo DRUG

This intervention will be used for individuals in arm A of the study who will receive a loading dose of colchicine (1.8 mg) on postoperative day 0, and will then be given placebo oral dextrose pills to take twice daily on postoperative days 1-3

Colchicine Loading Dose Only

Colchicine 1.8 mg + 0.6 mg DRUG

This intervention is will be given to patients in arm B of the study who will receive a loading dose of colchicine (1.8 mg) on postoperative day 0, followed by a maintenance does of colchicine (0.6 mg) to be taken twice daily on postoperative days 1-3.

Colchicine Loading Dose + Maintenance Dose

Dextrose Oral Placebo DRUG

This intervention will be for patients in arm C, the placebo arm. These patients will receive oral dextrose pills to be taken once on postoperative day 0, and twice daily on postoperative days 1-3.

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years or older undergoing elective total knee arthroplasty for osteoarthritis.

You may not qualify if:

• Subject has impaired hepatic function (Child-Pugh Class \>B)
• Subject has impaired renal function (GFR \< 60 ml/min/1.73 m2)
• Subject has known adverse reaction to colchicine
• Subject has chronic opioid use (Filled opioid medication twice within 6 months of surgical date)
• Subject is pregnant or expecting to become pregnant during the time of the study associated with colchicine exposure (postoperative days 0-3)
• Subject is unable to provide informed consent
• Subject is actively prescribed medication that interact with colchicine in a manner that would increase the risk of colchicine toxicity, i.e.:
• Antifungals: Ketoconazole, itraconazole, fluconazole, etc…
• Macrolides : Clarithromycin, erythromycin
• HIV protease : Ritonavir, Atazanavir, saquinavir, etc...
• Ca2+: Verapamil and Diltiazem
• Cyclosporine
• Danazol
• Amiodorone
• Quinidine

Sponsors & Collaborators

• Geisinger Clinic: lead
• St. Luke's Hospital, Kansas City, Missouri: collaborator

Related Publications (24)

• Nazia, S, Robinson, K, Terrell, J. Colchicine. StatPearls Publishing. Updated January 2025. Accessed March 20, 2025., https://www.ncbi.nlm.nih.gov/books/NBK431102/

  BACKGROUND

• Danoff JR, Goel R, Sutton R, Maltenfort MG, Austin MS. How Much Pain Is Significant? Defining the Minimal Clinically Important Difference for the Visual Analog Scale for Pain After Total Joint Arthroplasty. J Arthroplasty. 2018 Jul;33(7S):S71-S75.e2. doi: 10.1016/j.arth.2018.02.029. Epub 2018 Feb 22.

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• Heijman MWJ, Fiolet ATL, Mosterd A, Tijssen JGP, van den Bemt BJF, Schut A, Eikelboom JW, Thompson PL, van den Ende CHM, Nidorf SM, Popa CD, Cornel JH. Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements : Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial. Ann Intern Med. 2023 Jun;176(6):737-742. doi: 10.7326/M23-0289. Epub 2023 May 30.

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• Shvartz V, Le T, Enginoev S, Sokolskaya M, Ispiryan A, Shvartz E, Nudel D, Araslanova N, Petrosyan A, Donakanyan S, Chernov I, Bockeria L, Golukhova E. Colchicine in Cardiac Surgery: The COCS Randomized Clinical Trial. J Cardiovasc Dev Dis. 2022 Oct 20;9(10):363. doi: 10.3390/jcdd9100363.

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  PMID: 38505729 BACKGROUND

• Nidorf SM, Fiolet ATL, Mosterd A, Eikelboom JW, Schut A, Opstal TSJ, The SHK, Xu XF, Ireland MA, Lenderink T, Latchem D, Hoogslag P, Jerzewski A, Nierop P, Whelan A, Hendriks R, Swart H, Schaap J, Kuijper AFM, van Hessen MWJ, Saklani P, Tan I, Thompson AG, Morton A, Judkins C, Bax WA, Dirksen M, Alings M, Hankey GJ, Budgeon CA, Tijssen JGP, Cornel JH, Thompson PL; LoDoCo2 Trial Investigators. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020 Nov 5;383(19):1838-1847. doi: 10.1056/NEJMoa2021372. Epub 2020 Aug 31.

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  PMID: 28623906 BACKGROUND

• Meert L, Mertens MG, Meeus M, Vervullens S, Baert I, Beckwee D, Verdonk P, Smeets RJEM. Identification of Metabolic Factors and Inflammatory Markers Predictive of Outcome after Total Knee Arthroplasty in Patients with Knee Osteoarthritis: A Systematic Review. Int J Environ Res Public Health. 2023 May 11;20(10):5796. doi: 10.3390/ijerph20105796.

  PMID: 37239524 BACKGROUND

• Shah K, Mohammed A, Patil S, McFadyen A, Meek RM. Circulating cytokines after hip and knee arthroplasty: a preliminary study. Clin Orthop Relat Res. 2009 Apr;467(4):946-51. doi: 10.1007/s11999-008-0562-3. Epub 2008 Oct 22.

  PMID: 18941856 BACKGROUND

• Zhang FS, He QZ, Qin CH, Little PJ, Weng JP, Xu SW. Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review. Acta Pharmacol Sin. 2022 Sep;43(9):2173-2190. doi: 10.1038/s41401-021-00835-w. Epub 2022 Jan 19.

  PMID: 35046517 BACKGROUND

• Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain. 2002 Jul-Aug;18(4 Suppl):S3-13. doi: 10.1097/00002508-200207001-00002.

  PMID: 12479250 BACKGROUND

• Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br J Anaesth. 2018 Jun;120(6):1315-1334. doi: 10.1016/j.bja.2018.02.066. Epub 2018 Apr 12.

  PMID: 29793598 BACKGROUND

• Pepper AM, Mercuri JJ, Behery OA, Vigdorchik JM. Total Hip and Knee Arthroplasty Perioperative Pain Management: What Should Be in the Cocktail. JBJS Rev. 2018 Dec;6(12):e5. doi: 10.2106/JBJS.RVW.18.00023. No abstract available.

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  PMID: 37105325 BACKGROUND

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  PMID: 31733140 BACKGROUND

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• Maniar RN, Navaneedhan G, Ranvir S, Maniar AR, Dhiman A, Agrawal A. What Is the Normal Trajectory of Interleukin-6 and C-reactive Protein in the Hours and Days Immediately After TKA? Clin Orthop Relat Res. 2019 Jan;477(1):41-46. doi: 10.1097/CORR.0000000000000332.

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MeSH Terms

Conditions

Osteoarthritis, Knee; Pain, Postoperative

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Central Study Contacts

Ian Barr Medical Student, MS-2, BS

CONTACT

814-404-6616; ibarr1@som.geisinger.edu

John Mercuri Principal Investigator, MD

CONTACT

570-961-3823; Jmercuri1@geisinger.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: April 14, 2025
• First Posted: April 20, 2025
• Study Start: December 1, 2025
• Primary Completion: January 1, 2026
• Study Completion: March 1, 2026
• Last Updated: August 17, 2025

Record last verified: 2025-08