Intra-articular Polyacrylamide Hydrogel in Knee Osteoarthritis

December 24, 2024 updated by: Research Centre BIOFORM

Multicenter Double-blind Randomized Comparative Placebo-controlled Study of Efficacy and Safety of Intra-articular HBISA Endoprosthesis of Synovial Fluid (NOLTREX™) in Knee Osteoarthritis

The aim of this double-blinded controlled study is to assess clinical efficacy and safety of intra-articular HBISA Endoprosthesis of Synovial Fluid (polyacrylamide hydrogel) in comparison with placebo (0.9% sodium chloride solution) in Kellgren Lawrence radiological grade II-III knee osteoarthritis

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Polyacrylamide hydrogel (hereinafter - PAAG) is intended for a symptomatic effect leading to decrease of joint pain intensity and improvement of functional joint characteristics. Therefore PAAG is regarded as symptom-modifying therapy for joint osteoarthritis (hereinafter - OA). The aim of this study was to estimate efficacy and safety of intra-articular injections of PAAG in comparison with saline solution. Men and women above 50 years with verified knee osteoarthritis in accordance with the American College of Rheumatology (ACR) criteria were randomly assigned to one of 2 groups (PAAG or saline solution). Each patient received to the target knee joint one injection of 4.0 ml either PAAG or placebo with one-week interval. Course - 2 injections. To avoid the joint overfilling with the dense, slowly resorbing material in patients with a good clinical result, the course of injections was to be stopped. Primary and secondary efficacy endpoints, and safety parameters were assessed at weeks 6, 13 and 25 visits .

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
144

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Russian Federation
      • Moscow, Russian Federation
        • Non-budgetary healthcare facility "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
      • Omsk, Russian Federation
        • "Clinical Diagnostic Center "Ultramed", LLC
      • Saint Petersburg, Russian Federation
        • Private Healthcare Facilty "Clinical hospital "RZHD-Medicina" of the city Saint-Petersburg
      • Yaroslavl, Russian Federation
        • State budgetary healthcare facility of Yaroslavl Region "Clinical hospital №3"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

46 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women above 50 years;
  • Verified knee osteoarthritis in accordance with the ACR (knee pain combined with one of the following signs: age above 50 years, knee crepitus or morning joint stiffness lasting for less than 30 minutes combined with radiologic signs of knee osteoarthritis);
  • Kellgren Lawrence radiological grade II-III knee osteoarthritis with the predominant involvement of the medial tibiofemoral region of the knee joint;
  • Joint space width (JSW) of the target knee joint at least 2.5 mm.

Exclusion Criteria:

  1. History of any injury or surgical intervention on the target knee joint (except for diagnostic arthroscopy made not longer than 60 days at the study entry);
  2. Severe degenerative changes in the target knee joint determined as the joint space narrowing less than 2 mm;
  3. Varus or valgus deformation of the target knee joint;
  4. Instability of the target knee joint;
  5. Active inflammation of the target knee joint (edema, hyperemia, present effusion) at the study entry;
  6. Microcrystalline arthropathies;
  7. Systemic inflammatory disease (rheumatoid arthritis, systemic lupus erythematosus, etc.);
  8. Seronegative spondyloarthritis and reactive arthritis;
  9. Inflammatory diseases of the skin and soft tissues in the proposed injection site for the test MD or placebo in the target joint;
  10. History of venous thrombosis and thromboembolia;
  11. Coagulogram abnormalities (APTT, prothrombin time, prothrombin index, fibrinogen);
  12. Inflammatory changes in the complete blood count (leukocytosis, increase of erythrocyte sedimentation rate [ESR]);
  13. Platelet count abnormality (in accordance with the reference ranges of the local laboratory;
  14. Increase of rheumatoid factor level;
  15. Increase of uric acid level > 360 μmol/l;
  16. Diabetes mellitus;
  17. Hemophilia and other hemorrhagic diatheses, as well administration of anticoagulants and disaggregants;
  18. Positive results of HIV, HBs-Ag, anti-HCV, RW tests;

  19. Intra-articular injection to the target knee joint:

    • Noltrex - within 24 months prior patient's inclusion to the study;
    • hyaluronates - within 6 months prior patient's inclusion to the study;
    • glucocorticosteroids - within 1 month prior the study inclusion;
    • non-steroidal anti-inflammatory drugs (NSAID) - within 3 weeks prior patient's inclusion to the study.
  20. Oral administration of non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks prior the study inclusion;
  21. Necessity of systemic glucocorticosteroids in any dosage form;
  22. Paracetamol administration within 48 hours prior the study inclusion;
  23. Pregnancy and lactation;
  24. Hypersensitivity to components of the test MD or placebo;
  25. Severe liver disorder determined as the increase of one of the values: ALT, AST, ALP, total bilirubin, GGTP more than 3 times the upper limit of normal;
  26. Renal diseases with the glomerular filtration rate estimated per Cockraft-Gault formula less than 60 ml/min/1.73 m2 (III-V stage chronic renal disease [CRD]);
  27. Clinically manifest hip osteoarthritis;
  28. History of knee and coxofemoral endoprosthesis;
  29. Acute infectious diseases or infectious aggravations of chronic diseases (respiratory infections) within one month prior the study inclusion;
  30. Severe decompensated chronic or acute diseases and other conditions which, by the opinion of the study physician, may preclude the patient's participation in the study or affect the study results.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: NOLTREX™, OA grade II-III
72 patients with gonarthrosis grade II-III were randomised to receive PAHG
Device: hydrous biopolymer with silver ions "Argiform"
2 once-weekly intra-articular injections of NOLTREX™ 4.0 ml
Other Names:
  • Synovial fluid endoprosthesis NOLTREX™
  • polyacrylamide hydrogel with silver ions
Placebo Comparator: Placebo,OA grade II-III
72 patients with gonarthrosis grade II-III were randomised to receive saline solution
Device: saline solution
2 once-weekly intra-articular injections of saline solution 4 ml

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change of the Total WOMAC Score (WOMAC-T)
Time Frame: baseline (week 1), week 25
Mean change from baseline (week 1) to visit 5 (Week 25) in the total WOMAC score. Patients were asked to complete the questionnaire during the study visit 5. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-500 for Pain, 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse pain, stiffness, and functional limitations. A sum of the scores for all three subscales gives a total WOMAC score (0-2400), where 0 represents the best health status and 2400 the worst possible status. The higher the score, the poorer the function.
baseline (week 1), week 25

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change of the Total WOMAC Score (WOMAC-T)
Time Frame: baseline (week 1), week 13 (visit 4)
Mean change from baseline (week 1) to Week 13 in the total WOMAC score. Patients were asked to complete the questionnaire during the study visits 1, 3, 4, 5. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). The WOMAC consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The test questions are scored on a scale of 0-4, which correspond to: None (0), Mild (1), Moderate (2), Severe (3), and Extreme (4). The scores for each subscale are summed up, with a possible score range of 0-20 for Pain, 0-8 for Stiffness, and 0-68 for Physical Function. Higher scores represent worse pain, stiffness, and functional limitations. A sum of the scores for all three subscales gives a total WOMAC score (0-96), where 0 represents the best health status and 96 the worst possible status. The higher the score, the poorer the function.
baseline (week 1), week 13 (visit 4)
The Pain Subscale Score WOMAC-A Changes
Time Frame: baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
Mean change from baseline (week 1) to week 6 (visit 3), 13 (visit 4) and 25 (visit 5) in the WOMAC Pain score (WOMAC-A). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a set of standardized questionnaires used by health professionals to evaluate pain, stiffness and physical functioning of the joints in patients with knee and/or hip osteoarthritis. The WOMAC Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS. The WOMAC pain scale consists of five items: (1) walking on flat ground; (2) going up or down stairs; (3) at night while in bed; (4) sitting or lying; and (5) standing upright. The scores for the Pain subscale are summed up, with a possible score range of 0-500. Higher scores represent worse pain. Patients were asked to complete the questionnaire during the study visits 1, 3, 4, 5.
baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
The Stiffness (WOMAC-B) and Functionality (WOMAC-C) Subscale Scores Changes
Time Frame: baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
Mean change from baseline (week 1) to week 6 (visit 3), 13 (visit 4) and 25 (visit 5) in the WOMAC Stiffness (WOMAC-B) and WOMAC Physical Function (WOMAC-C) scores. Patients were asked to complete the questionnaire during the study visit 5. The Western Ontario and McMaster Universities Osteoarthritis Index Version 3.1 Visual Analog Scale Format (WOMAC VA 3.1) applies a 100 mm VAS and consists of three subscales: pain (5 questions), stiffness (2 questions), and physical function (17 questions). The scores for each subscale are summed up, with a possible score range of 0-200 for Stiffness, and 0-1700 for Physical Function. Higher scores represent worse stiffness and functional limitations. The higher the score, the poorer the function.
baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
Patient Assessment of Treatment Efficacy
Time Frame: Week 6, Week 13 and Week 25
Patient satisfaction with treatment was measured by a 6-point scale Likert scale (evident aggravation, aggravation, without changes, weak improvement, improvement, significant improvement) at the study visits 3 (week 6), 4 (week 13) and 5 (week 25).
Week 6, Week 13 and Week 25
Investigator Assessment of Treatment Efficacy
Time Frame: Week 6, Week 13 and Week 25
Investigator satisfaction with treatment was measured by a 6-point scale Likert scale (evident aggravation, aggravation, without changes, weak improvement, improvement, significant improvement) at the study visits 3 (week 6), 4 (week 13) and 5 (week 25).
Week 6, Week 13 and Week 25
Assessment of the Total Number of NSAID Tablets Taken
Time Frame: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
A patient diary was used to capture data about the number of NSAID Tablets Taken. In case of paracetamol ineffectiveness and pain persistence patient was allowed to take Protocol-permitted NSAID in certain doses.
week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
Assessment of the Total Number of Paracetamol Tablets Taken
Time Frame: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
A patient diary was used to capture data about the number of paracetamol tablets taken.
week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
Patient Exclusion Rates Due to Safety
Time Frame: Week 25
According to protocol the reasons for withdrawal included health status deterioration, investigator's decision, need in paracetamol use ≥4 days a week during 2 consecutive weeks, individual intolerance or contraindications to the study MD, placebo, paracetamol or any of the protocol-permitted NSAIDs; development of a AE/SAE requiring examination and/or treatment that can significantly affect the study procedures
Week 25
Exclusion Rate Due to Poor Patient Compliance
Time Frame: Week 25
According to the protocol the reasons for patients drop-out included major protocol deviations (poor compliance) and withdrawal of informed consent.
Week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Research Centre BIOFORM

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Vladimir V Popov, DSc, Non-budgetary HCF "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 29, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 2, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 17, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 26, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 1, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 24, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IA/PAAG-SI/OA/2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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