ArticleRheumatology and therapy2021
Knee Osteoarthritis Pain Management with an Innovative High and Low Molecular Weight Hyaluronic Acid Formulation (HA-HL): A Randomized Clinical Trial.
Article in Rheumatology and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03200288 (A Phase 3,Randomized,Double-blind,Placebo-controlled Study to Evaluate the Clinical Performance and Safety of an Intra-articular Solution of High and Low Molecular Weight Hyaluronic Acid), which is not on this map. Cited by 16 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3,Randomized,Double-blind,Placebo-controlled Study to Evaluate the Clinical Performance and Safety of an Intra-articular Solution of High and Low Molecular Weight Hyaluronic Acid (HL-01) in the Treatment of Pain in Symptomatic Knee Osteoarthritis
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- The Efficacy of Polydioxanone Sutures in Treating Mild-to-Moderate Knee Osteoarthritis: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Viscosupplementation for knee osteoarthritis: systematic review and meta-analysis.BMJ (Clinical research ed.) · 2022Pooled it
- Intra-articular injection of high versus low molecular weight hyaluronic acid in adhesive capsulitis; randomized trial.Future science OA · 2026Article
- Expert consensus on hyaluronic acid injections for knee osteoarthritis: a patient-centered approach.Aging clinical and experimental research · 2026Review
- Impact of Symptomatic Slow-Acting Drugs on Inflammatory Pathways in Osteoarthritis: Therapeutic Advances and Future Challenges.ACS pharmacology & translational science · 2025Review
- Placebo response to intra-articular injections in knee osteoarthritis: magnitude, evolution over time, and influencing factors. A systematic review and meta-analysis with meta-regression.EFORT open reviews · 2025Article
- The Efficacy and Safety of Single Injections of Hybrid HA in the Treatment of Symptomatic Knee Osteoarthritis: A Case Series.Rheumatology and therapy · 2025Article
- Safety and Efficacy of Hybrid Cooperative Complexes of Sodium Hyaluronate and Sodium Chondroitin for the Treatment of Patients with Symptomatic Knee Osteoarthritis.Rheumatology and therapy · 2024Article
- Safety of Epidural Hyaluronic Acid Injections in Managing the Symptoms of Lumbar Foraminal Stenosis: A Prospective Preliminary Study.Journal of clinical medicine · 2023Article
- Use of intra-articular hyaluronic acid in knee osteoarthritis or osteoarthritis.Revista da Associacao Medica Brasileira (1992) · 2023Article
- Comparison of Intra-articular Hyaluronic Acid and Platelet-Rich Plasma Injection in Knee Osteoarthritis: Do the Results Differ in Geriatric Patients? A Retrospective Observational Study.Annals of geriatric medicine and research · 2022Article
- Review
- Health Economic Evaluation of a High and Low Molecular Weight Hyaluronic Acid Formulation for the Treatment of Knee Osteoarthritis. Post Hoc Analyses from a Randomized Clinical Trial.Rheumatology and therapy · 2022Article
- A Review of the Clinical Effectiveness and Safety of Hybrid Cooperative Complexes in Intra-articular Viscosupplementation.Rheumatology and therapy · 2022Review
- A narrative review of the progress in the treatment of knee osteoarthritis.Annals of translational medicine · 2022Review
- The role and impact of health economics in the optimization of patient care in osteoarthritis: insights from a practical example.Global & regional health technology assessmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe objective of this study was to compare a single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) versus placebo in treating moderate-to-severe symptomatic knee osteoarthritis.
methodsSubjects with primary osteoarthritis knee pain (Kellgren and Lawrence grade 2-3) were randomly assigned to intra-articular HA-HL or placebo in a prospective, double-blind, 24-week study. The primary outcome variable was change from screening to week 24 of a Visual Analogue Scale (VAS) pain score. Secondary outcomes included Lequesne's algofunctional index, EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) response and rescue medication usage.
resultsIn a total of 692 randomized patients, a rapid decrease was observed in mean VAS pain score from baseline to week 1 (26 ± 24 mm in the HA-HL group vs. 23 ± 23 mm in the placebo group); pain intensity continued to decrease during 24 weeks of follow-up, reaching a mean change from baseline of 35 ± 28 mm vs. 32 ± 27 mm at week 24. Mixed model analysis demonstrated statistically significant differences between groups in favor of the HA-HL group at weeks 1, 6, 12, and 24. HA-HL was also more effective than placebo in improving Lequesne's algofunctional index, OMERACT-OARSI response, and health-related quality of life. The use of rescue medication (paracetamol 500 mg tablets; ≤ 6 per day) was lower in the HA-HL group. Both treatments were similarly well tolerated.
conclusionsA single intra-articular injection of an innovative high and low molecular weight hyaluronic acid formulation (HA-HL) is effective in providing fast, sustained, and clinically relevant reductions in pain, functional limitation, and health-related quality of life that were apparent at 1 week after the intra-articular injection and maintained throughout the 24-week follow-up in subjects with painful knee osteoarthritis, with a good safety profile.
trial registrationClinicalTrials.gov identifier: NCT03200288.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.