Perioperative Colchicine for TKA

Официальное название

Effect of Colchicine in the Perioperative Period on Reducing Post-Operative Pain in Total Knee Arthroplasty

Обзор

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.

Подробное описание

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 TKA.

In doing so, we will utilize a 3-arm approach with two experimental groups and one placebo group. Qualifying subjects will be randomized 1:1:1 to Group A receiving a 1.8 mg loading dose of colchicine, Group B receiving the same loading dose + 0.6 mg maintenance dose of colchicine to be taken twice daily, and Group C receiving a placebo.

Regarding study procedures, standard preoperative and intraoperative procedures will be employed to ensure experimental and control groups have a nearly equivalent experience before the intervention. Subjects will be discharged with the same ambulation instructions and physical therapy regimens. Aside from the experimental drug, patients will receive the same postoperative pain medications upon discharge.

Research staff in the Geisinger pharmacy will receive and prepare the oral medication for dispensing, which will include randomizing identification numbers to colchicine or placebo, labeling packages with study identification numbers and subject information, and ensuring there is no visible method to discern colchicine from placebo. Colchicine is to be stored at room temperature.

Providers and subjects will be blinded regarding whether the subject will receive a colchicine loading dose + the placebo pills for maintenance doses, a colchicine loading dose + colchicine for maintenance doses, or the placebo pills for both. Group A will receive a 1.8 mg loading dose of colchicine by mouth on postoperative day 0 and will be instructed to take a placebo by mouth twice daily on postoperative days 1-3. Group B will receive a 1.8 mg loading dose of colchicine by mouth on postoperative 0 and will be instructed to take a 0.6 mg maintenance dose of colchicine by mouth twice daily on postoperative days 1-3. Group C will receive placebo dextrose pills by mouth on postoperative day 0 and will be instructed to take the placebo by mouth twice daily on postoperative days 1-3. Subjects will be sent home with an adequate supply of pills for postoperative days 1-3 and instructions on use.

The procedure for measuring the study variables is as follows:

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. The journal will also include a box for subjects to record the total pills of the prescribed postoperative opioid they have taken each day on postoperative days 1-3. Lastly, the journal will include a checkbox at the end for subjects to record whether they have experienced known colchicine-related side effects on postoperative days 1-3 such as nausea, vomiting, diarrhea, and abdominal pain. For evaluation of KOOS-JR scores and knee flexion, subjects will complete the 7-question KOOS-JR questionnaire at their 2-, 6-, and 12-week post-operative visits, and at these visits, a member of the research staff will determine the subject's knee flexion. Lastly, regarding the assessment of 90-day postoperative complications, the researchers will conduct a review of the subject's EHR.

Вмешательства

• Препарат Colchicine 1.8 mg (loading dose) + Dextrose Oral Placebo
  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
• Препарат Colchicine 1.8 mg + 0.6 mg
  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.
• Препарат Dextrose Oral Placebo
  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.

Первичные конечные точки

• Postoperative VAS pain score [Срок оценки: From postoperative day 0 through postoperative day 4.]

Вторичные конечные точки (5)

• Daily Opioid Usage [Срок оценки: From postoperative day 0 through postoperative day 3.]
• Postoperative KOOS-JR Score [Срок оценки: From postoperative day 0 through postoperative week 12.]
• Postoperative Knee Flexion [Срок оценки: Postoperative day 0 through postoperative week 12.]
• 90 day postoperative complications [Срок оценки: Postoperative day 0 to postoperative day 90]
• Colchicine Related Side Effects [Срок оценки: Postoperative day 0 through postoperative day 3.]

Критерии участия

Критерии включения

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

Критерии исключения

• 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
• Anti-hepaciviral combinations
• Grapefruit juice
• Statins: atorvastatin, lovastatin, simvastatin, etc…
• Gemfibrozil and other fibrates
• Digoxin

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Факторный дизайн

Маскирование

Тройное слепое

Основная цель

Поддерживающая терапия

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Nazia, S, Robinson, K, Terrell, J. Colchicine. StatPearls Publishing. Updated January 2025. Accessed March 20, 2025., https://www.ncbi.nlm.nih.gov/books/NBK431102/
• 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. PMID 29567002
• Huang ZY, Huang Q, Wang LY, Lei YT, Xu H, Shen B, Pei FX. Normal trajectory of Interleukin-6 and C-reactive protein in the perioperative period of total knee arthroplasty under an enhanced recovery after surgery scenario. BMC Musculoskelet Disord. 2020 Apr 21;21(1):264. doi: 10.1186/s12891-020-03283-5. PMID 32316949
• 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. PMID 37247416
• 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. PMID 36286314
• Akl E, Sahami N, Labos C, Genest J, Zgheib A, Piazza N, Jolly S. Meta-Analysis of Randomized Trials: Efficacy and Safety of Colchicine for Secondary Prevention of Cardiovascular Disease. J Interv Cardiol. 2024 Mar 12;2024:8646351. doi: 10.1155/2024/8646351. eCollection 2024. PMID 38505729
• 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. Colc PMID 32865380
• Si HB, Yang TM, Zeng Y, Zhou ZK, Pei FX, Lu YR, Cheng JQ, Shen B. Correlations between inflammatory cytokines, muscle damage markers and acute postoperative pain following primary total knee arthroplasty. BMC Musculoskelet Disord. 2017 Jun 17;18(1):265. doi: 10.1186/s12891-017-1597-y. PMID 28623906

Идентификаторы

NCT: NCT06936709 · 2024-0488

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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