Efficacy of Diosmin and Hesperidin on Early Rehabilitation After Total Knee Arthroplasty

Efficacy of Diosmin and Hesperidin on Early Rehabilitation After Primary Total Knee Arthroplasty

The goal of this clinical trial is to find out the efficacy of diosmin and hesperidin on postoperative early rehabilitation after primary total knee arthroplasty. The main questions it aims to answer are:

Does diosmin and hesperidin combined drug decreases the lower extremity swelling, pain and increases the range of motion after primary total knee arthroplasty surgery compared to standard therapy group? Does diosmin and hesperidin combined drug decreases inflammation after total knee arthroplasty surgery.

Participants will take diosmin and hesperidin in addition to standard therapy for 14 days after total knee arthroplasty surgery. Lower extremity swelling, pain and range of motion of the patients will be recorded in every visit.

Study Overview

• Status: Completed
• Conditions: Total Knee Arthroplasty; Venous Insufficiency of Leg
• Intervention / Treatment: Drug: Diosmin and Hesperidin Combination

• Study Type: Observational
• Enrollment (Actual): 190

Contacts and Locations

Study Locations

• Turkey
  • Yenimahalle
    • Ankara, Yenimahalle, Turkey, 06070
      • Ankara Etlik City Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study included patients who underwent unilateral total knee arthroplasty.

Description

Inclusion Criteria:

• Patients who underwent unilateral primary total knee replacement surgery
• Patients who are functionally ASA 1, ASA 2 or ASA 3.

Exclusion Criteria:

• Patients >80 years or <18 years of age
• Patients with liver insufficiency
• Patients with allergy to diosmin or hesperidin
• Patients which are not capable to communicate

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study group; Participants will take diosmin and hesperidin combination in addition to standard therapy for 14 days after total knee replacement surgery.	Drug: Diosmin and Hesperidin Combination; Participants will take diosmin and hesperidin combination for 14 days after total knee replacement surgery.
Control group; Participants will only take standard therapy for 14 days after total knee replacement surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lower extremity swelling	Lower extremity swelling is measured by measuring extremity diameters from 3 points (below patella, patella and above patella) and noted. Then percentage of increment or decrement of diameters is measured.	From enrollment to the end of the treatment at 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain	The Visual Analog Scale is used to describe patients' pain. It is a scale that describes pain by giving numbers from 0 to 10. 0 means no pain and 10 means extreme pain.	From enrollment to the end of the treatment at 2 weeks
Range of motion	Knee range of motion is measured with goniometer.	From enrollment to the end of the treatment at 2 weeks
Blood C-reactive protein value as an inflammotory marker		From enrollment to the end of the treatment at 2 weeks
Blood erythrocyte sedimentation rate as an inflammotory marker		From enrollment to the end of the treatment at 2 weeks
Blood neutrophil/lymphocyte rate as an inflammatory marker		From enrollment to the end of the treatment at 2 weeks
Panimmune value (neutrophil x platelet x monocyte / lymphocyte) as an inflammatory marker		From enrollment to the end of the treatment at 2 weeks
The systemic immune-inflammation index (neutrophils × platelets/lymphocytes) as an inflammatory marker		From enrollment to the end of the treatment at 2 weeks

Collaborators and Investigators

• Sponsor: Ankara Etlik City Hospital

Publications and helpful links

General Publications

• Nicolaides AN. The Benefits of Micronized Purified Flavonoid Fraction (MPFF) Throughout the Progression of Chronic Venous Disease. Adv Ther. 2020 Feb;37(Suppl 1):1-5. doi: 10.1007/s12325-019-01218-8. Epub 2020 Jan 22.
• Wang Q, Jin Q, Cai L, Zhao C, Feng P, Jia J, Xu W, Qian Q, Ding Z, Xu J, Gu C, Zhang S, Shi H, Ma H, Deng Y, Zhang T, Song Y, Wang Q, Zhang Y, Zhou X, Pei L, Yang Y, Liang J, Jiang T, Li H, Liu H, Wu L, Kang P. Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial. J Bone Joint Surg Am. 2024 Mar 20;106(6):492-500. doi: 10.2106/JBJS.23.00854. Epub 2023 Dec 18.
• Fotiadis E, Kenanidis E, Samoladas E, Chytas A, Lyrtzis C, Koimtzis M, Chalidis B. Are venotonic drugs effective for decreasing acute posttraumatic oedema following ankle sprain? A prospective randomized clinical trial. Arch Orthop Trauma Surg. 2011 Mar;131(3):389-92. doi: 10.1007/s00402-011-1266-9. Epub 2011 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2024
• Primary Completion (Actual): June 10, 2025
• Study Completion (Actual): June 10, 2025

Study Registration Dates

• First Submitted: December 18, 2024
• First Submitted That Met QC Criteria: December 21, 2024
• First Posted (Actual): December 31, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2025
• Last Update Submitted That Met QC Criteria: July 14, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Total knee arthroplasty; inflammation; pain management; venous insufficiency; lower extremity swelling
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Venous Insufficiency
• Other Study ID Numbers: 2024-1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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