Single vs Triple Hyaluronic Acid in Knee Osteoarthritis (DR-HAKOA)

University of Erlangen-Nürnberg Medical School

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: Osteoarthritis, Knee

Treatments: Drug: One intra-articular hyaluronic acid (HA) injection; Drug: Three intra-articular hyaluronic acid (HA) injections

Study type: Interventional

Funder types: Other

Identifiers

NCT07352540

25-275_1-Bm

Details and patient eligibility

About

The goal of this clinical trial is to directly compare two hyaluronic acid injection protocols in adults with knee osteoarthritis: a single intra-articular injection of Innoryos 2.5% (Single-Shot) and a three-week injection series of Innoryos 2.2% (Triple-Shot). The study aims to determine whether the single injection provides comparable safety, pain relief, and improvement in knee function to the triple-injection protocol.

The main questions are:

• How do the single-shot and triple-shot protocols compare in terms of pain reduction and functional improvement?
• How do their safety and tolerability profiles compare?
• What medical problems occur with each protocol? Participants (n = 46) will receive either the single 4.8 ml injection or three weekly 2 ml injections. They will attend clinic visits at baseline, Week 6, Week 12, and Week 24 for assessments including WOMAC score, 7-day pain diary, functional and strength tests, and MRI scans of the knee.

This single-center, partially blinded, randomized study will provide a direct comparison of the two HA injection protocols, assessing whether the single-shot approach is as safe and effective as the triple-shot regimen, while potentially offering a more convenient, patient-friendly treatment.

Full description

Background:

Knee osteoarthritis (gonarthrosis) is a prevalent degenerative joint disease characterized by cartilage loss, joint pain, stiffness, and functional impairment, which significantly affects mobility and quality of life. Intra-articular injections of hyaluronic acid (HA) are a well-established conservative therapy to reduce pain, improve function, and potentially delay surgical interventions. Various HA formulations and injection protocols exist, differing in molecular weight, concentration, and dosing schedules. Optimizing treatment in terms of efficacy, safety, patient convenience, and cost-effectiveness remains a key clinical goal.

Objective:

This study aims to compare the safety, tolerability, and efficacy of a single intra-articular injection of Innoryos 2.5% (Single-Shot) with a standard three-week injection regimen of Innoryos 2.2% (Triple-Shot) in adults with moderate to severe knee osteoarthritis. The primary focus is on safety and pain reduction, with secondary outcomes including functional improvement, leg muscle strength, and structural assessment of the knee joint via MRI.

Study Design:

This is a single-center, randomized, partially blinded, parallel-group clinical intervention study including 46 participants. Patients are randomized using block randomization stratified by baseline WOMAC total score to ensure balanced distribution of baseline pain and functional impairment. Patients and treating physicians are aware of treatment allocation, while all personnel performing functional tests, MRI assessments, data entry, and statistical analyses are blinded to minimize bias.

Participants:

Adults aged 40-70 years with radiographically confirmed moderate to severe knee osteoarthritis, experiencing knee pain for at least three months and on at least 50% of days in the prior month. Key exclusion criteria include grade 4 osteoarthritis, non-osteoarthritic knee pain, other rheumatic diseases, recent HA or corticosteroid injections, recent trauma or surgery, coagulopathies, autoimmune disorders, pregnancy or lactation, and contraindications for MRI.

Interventions:

• Single-Shot Group: One intra-articular injection of Innoryos 2.5% (4.8 ml)
• Triple-Shot Group: Three intra-articular injections of Innoryos 2.2% (2 ml each) at weekly intervals

Outcomes:

The primary outcome is total WOMAC score. Secondary outcomes include WOMAC subscales, VAS pain diary, functional performance, leg muscle strength, MRI-detected structural changes, and safety/tolerability parameters.

Assessments:

Participants are assessed at baseline, Week 6, Week 12, and Week 24.

• WOMAC questionnaire (baseline, Week 6, Week 12, and Week 24): Pain, stiffness, and functional limitation
• Pain diary (VAS) (baseline, Week 6, Week 12, and Week 24): Daily for 7 days at each assessment (~1 min/day)
• Functional and strength tests (baseline, Week 6, Week 12): Chair Stand Test, Timed Up and Go Test, isokinetic leg press (~30 min per session)
• MRI (baseline, Week 6, Week 12): Baseline and Week 12 for structural assessment (~90 min including functional tests)
• Safety monitoring: Adverse events, medication use, compliance, drop-outs

Significance:

This study provides high-quality evidence for the direct comparison of single-shot versus triple-shot HA injection protocols in knee osteoarthritis. By using stratified randomization based on baseline WOMAC total score and blinded assessment of outcomes, the trial ensures unbiased evaluation. Demonstration of comparable safety and efficacy of the single-shot regimen could offer a more convenient, patient-friendly, and potentially safer therapeutic option, optimizing conservative management for patients with knee osteoarthritis.

intra-articular injection of Innoryos 2.5% (Single-Shot) with a standard three-week injection regimen of Innoryos 2.2% (Triple-Shot) in adults with moderate to severe knee osteoarthritis. The primary focus is on safety and pain reduction, with secondary outcomes including functional improvement, leg muscle strength, and structural assessment of the knee joint via MRI.

Study Design:

This is a single-center, randomized, partially blinded, parallel-group clinical intervention study including 46 participants. Patients are randomized using block randomization stratified by baseline WOMAC total score to ensure balanced distribution of baseline pain and functional impairment. Patients and treating physicians are aware of treatment allocation, while all personnel performing functional tests, MRI assessments, data entry, and statistical analyses are blinded to minimize bias.

Participants:

Adults aged 40-70 years with radiographically confirmed moderate to severe knee osteoarthritis, experiencing knee pain for at least three months and on at least 50% of days in the prior month. Key exclusion criteria include grade 4 osteoarthritis, non-osteoarthritic knee pain, other rheumatic diseases, recent HA or corticosteroid injections, recent trauma or surgery, coagulopathies, autoimmune disorders, pregnancy or lactation, and contraindications for MRI.

Enrollment: 46 estimated patients

Sex: All

Ages: 40 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adults aged 40-70 years
• Radiographically confirmed moderate to severe knee osteoarthritis
• Knee pain for ≥3 months
• Pain on ≥50% of days in past 30 days
• Able to provide informed consent

Exclusion criteria

• Grade 4 osteoarthritis (full-thickness cartilage loss)
• Non-osteoarthritic knee pain
• Other rheumatic diseases (e.g., rheumatoid arthritis, fibromyalgia)
• HA injection <6 months or corticosteroid injection <3 months in target knee
• Recent trauma or surgery of affected knee (<6 months)
• Coagulopathy or bleeding disorder
• Autoimmune or relevant systemic disease
• Dermatologic infection at injection site
• Pregnancy or lactation
• Opioid or oral corticosteroid use
• Contraindications to MRI (pacemaker, intracorporeal metal, claustrophobia)
• Expected absence during study period or noncompliance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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46 participants in 2 patient groups

Three intra-articular HA injections

Active Comparator group

Description:

Three intra-articular injections of Innoryos 2.2% (2 ml each) in the knee joint at weekly intervals

Treatment:

Drug: Three intra-articular hyaluronic acid (HA) injections

One intra-articular HA injection

Experimental group

Description:

One intra-articular injection of Innoryos 2.5% (4.8 ml) in the knee joint

Treatment:

Drug: One intra-articular hyaluronic acid (HA) injection