Perioperative Colchicine for TKA

Phase 4

Not yet recruiting

• Conditions: Osteoarthritis of Knee; Recovery Following Primary Total Knee Arthroplasty; Perioperative Pain Control
• Interventions: Drug: Colchicine 1.8 mg (loading dose) + Dextrose Oral Placebo; Drug: Colchicine 1.8 mg + 0.6 mg; Drug: Dextrose Oral Placebo

• Registration Number: NCT06936709
• Lead Sponsor: Geisinger Clinic

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-14
• Study First Submitted QC: 2025-04-14
• Study First Posted: 2025-04-20
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-24
• Study Start: 2025-07-01
• Primary Completion: 2026-01-01
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Colchicine Loading Dose Only	Colchicine 1.8 mg (loading dose) + Dextrose Oral Placebo	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.
Colchicine Loading Dose + Maintenance Dose	Colchicine 1.8 mg + 0.6 mg	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.
Placebo Group	Dextrose Oral Placebo	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.

Primary Outcome Measures

Name	Time	Method
Postoperative VAS pain score	From postoperative day 0 through postoperative day 4.	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.

Secondary Outcome Measures

Name	Time	Method
Daily Opioid Usage	From postoperative day 0 through postoperative day 3.	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 the total pills of the prescribed postoperative opioid they have taken each day on postoperative days 1-3.
Postoperative KOOS-JR Score	From postoperative day 0 through postoperative week 12.	Subjects will complete the 7-question KOOS-JR questionnaire at their 2-, 6-, and 12-week post-operative visits. Scoring ranges from 0-28, measuring variables from 0 (none) to 4 (extreme). Questions asked are: How severe is your knee stiffness after first wakening in the morning? What amount of knee pain have you experienced the last week during the following activities?; * Twisting/pivoting on your knee; * Straightening knee fully; * Going up or down stairs; * Standing upright And the what degree of difficulty have you had with the following activities?; * Rising from sitting; * Bending to floor/pick up an object
Postoperative Knee Flexion	Postoperative day 0 through postoperative week 12.	Subject's knee flexion will be assessed at their 2-, 6-, and 12- week postoperative visits to assess recovery from their TKA. Values will be recording in degree of flexion, representing their range of motion.
90 day postoperative complications	Postoperative day 0 to postoperative day 90	Subject's 90-day postoperative complications such as ED visits, unplanned readmission, joint infection, wound dehiscence, deep vein thrombosis, pulmonary embolism, or return to OR, etc. Assessment of these complications will be done through a chart review of the subject's electronic health records.
Colchicine Related Side Effects	Postoperative day 0 through postoperative day 3.	The assessment of colchicine related side effects such as diarrhea, vomiting, abdominal pain, nausea, fatigue, headache, and pharyngolaryngeal pain will be recorded by subjects in the postoperative journal that they will receive on postoperative day 0. A checkbox will be present for each known side-effect for patients to self-report if they have had any of the aforementioned symptoms.