Injection Site Diversity Influences HA Distribution and Clinical Results in CP and KOA

Injection Site Diversity Influences Sodium Hyaluronate Distribution and Its Clinical Results in Management of Chondromalacia Patellae and Knee Osteoarthritis: A Preliminary, Multi-central, Randomize-controlled Serial Trial

In order to investigate the difference of intra-articular hyaluronate's distribution and compare the clinical outcomes of viscosupplementation for mild-to-moderate knee osteoarthritis (mKOA) between the anteromedial (AM) and medial midpatellar (MMP) approach groups. This study included two parts, cadaver study (n=64) and random controlled trial (n=100). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale in the cadaver study. The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index and the follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections in the random controlled trial.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee; Hyaluronan
• Intervention / Treatment: Procedure: anteromedial (AM) portal; Procedure: medial midpatellar (MMP) portal

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic unilateral mild-to-moderate knee osteoarthritis (mKOA) that were defined by the American College of Rheumatology criteria
• Kellgren-Lawrence grade 2 or 3
• Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index (Likert version 3.1) pain subscale reached 10 or greater

Exclusion Criteria:

• Pregnancy, acute fracture, rheumatoid arthritis, gouty arthritis, traumatic arthritis, inflammatory arthritis
• Oral Celebrex within 2 weeks, HA and lidocaine allergy, intra-articular injection of HA or corticosteroid to the target knee within the past 6 months
• Surgery in the target knee within the past 6 months, OA of the target knee with K-L grade 4
• Active liver and renal disease, cardiovascular and cerebrovascular disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AM groups in cadavers study; 32 osteoarthritic knees of cadavers were randomly assigned to the AM group (injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale.	Procedure: anteromedial (AM) portal; injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion
Experimental: MMP groups in cadavers study; 32 osteoarthritic knees of cadavers were randomly assigned to the MMP group (injection medial under horizontal patella midline was administrated with the lower limb extension). Hyaluronic acid (HA) traced by methylene blue was injected into the knee, and the intra-articular distribution of HA was assessed using a five-point scale.	Procedure: medial midpatellar (MMP) portal; injection medial under horizontal patella midline was administrated with the lower limb extension
Experimental: AM groups in random controlled trial; 50 patients with unilateral mKOA were enrolled and randomly into the AM group (injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion).The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index. The follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections.	Procedure: anteromedial (AM) portal; injection medial from patella tendon towards intercondylar notch was performed with the target knee 90° flexion
Experimental: MMP groups in random controlled trial; 50 patients with unilateral mKOA were enrolled and randomly into the MMP group (injection medial under horizontal patella midline was administrated with the lower limb extension).The clinical outcomes of 5-weekly injections of HA were evaluated by WOMAC and Lequesne index. The follow-up times were at weeks 1, 2, 3, 4, 5, 14, and 24 after the injections.	Procedure: medial midpatellar (MMP) portal; injection medial under horizontal patella midline was administrated with the lower limb extension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	baseline before the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	1 week after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	2 weeks after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	3 weeks after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	4 weeks after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	5 weeks after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	14 weeks after the first injection
WOMAC (Likert version 3.1)	WOMAC included three subscales: pain, stiffness and function, and each subscale was graded using a 5-point Likert scale (0=none, 1=mild, 2=moderate, 3=severe, 4=extreme). Pain index score ranges from 0 to 20, whereas the stiffness score ranges from 0 to 8 and the function score ranges from 0 to 68. The reliability of the three subscales of the WOMAC was 0.82, 0.68 and 0.74, respectively.	24 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	baseline before the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	1 week after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	2 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	3 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	4 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	5 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	14 weeks after the first injection
Lequesne index	The Lequesne index questionnaire included 10 questions about pain, stiffness and function. The score ranges from 0 (no pain, no disability) to 24 (maximum pain, stiffness and disability), and its reliability was 0.95.	24 weeks after the first injection

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2014
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: June 30, 2018
• First Submitted That Met QC Criteria: July 16, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Viscosupplementation; Hyaluronate; Distribution; Knee osteoarthritis; Injection approach
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee
• Other Study ID Numbers: NFEC-2014-074

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