OsteoarthritisNCT03897686
Intra-articular Polyacrylamide Hydrogel in Knee Osteoarthritis
A study testing hydrous biopolymer with silver ions "Argiform" and saline solution in people with Osteoarthritis, run by Research Centre BIOFORM at 4 sites in Russia.
Trial summary
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 Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- hydrous biopolymer with silver ions "Argiform" and saline solution
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 4 sitesRussia
- Study dates
- 29 Nov 2019to 17 Dec 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
- Severe degenerative changes in the target knee joint determined as the joint space narrowing less than 2 mm;
- Varus or valgus deformation of the target knee joint;
- Instability of the target knee joint;
- Active inflammation of the target knee joint (edema, hyperemia, present effusion) at the study entry;
- Microcrystalline arthropathies;
Show all 34Show fewer
- Systemic inflammatory disease (rheumatoid arthritis, systemic lupus erythematosus, etc.);
- Seronegative spondyloarthritis and reactive arthritis;
- Inflammatory diseases of the skin and soft tissues in the proposed injection site for the test MD or placebo in the target joint;
- History of venous thrombosis and thromboembolia;
- Coagulogram abnormalities (APTT, prothrombin time, prothrombin index, fibrinogen);
- Inflammatory changes in the complete blood count (leukocytosis, increase of erythrocyte sedimentation rate [ESR]);
- Platelet count abnormality (in accordance with the reference ranges of the local laboratory;
- Increase of rheumatoid factor level;
- Increase of uric acid level > 360 μmol/l;
- Diabetes mellitus;
- Hemophilia and other hemorrhagic diatheses, as well administration of anticoagulants and disaggregants;
- Positive results of HIV, HBs-Ag, anti-HCV, RW tests;
- 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.
- Oral administration of non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks prior the study inclusion;
- Necessity of systemic glucocorticosteroids in any dosage form;
- Paracetamol administration within 48 hours prior the study inclusion;
- Pregnancy and lactation;
- Hypersensitivity to components of the test MD or placebo;
- 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;
- 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]);
- Clinically manifest hip osteoarthritis;
- History of knee and coxofemoral endoprosthesis;
- Acute infectious diseases or infectious aggravations of chronic diseases (respiratory infections) within one month prior the study inclusion;
- 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.
Trial locations and contacts
4 sites in 1 country.
Russia4 sites
Non-budgetary healthcare facility "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
Moscow
"Clinical Diagnostic Center "Ultramed", LLC
Omsk
Private Healthcare Facilty "Clinical hospital "RZHD-Medicina" of the city Saint-Petersburg
Saint Petersburg
State budgetary healthcare facility of Yaroslavl Region "Clinical hospital №3"
Yaroslavl
About this study
Official title: 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
Read the 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 .
- Conditions
- Osteoarthritis
- Being tested
- hydrous biopolymer with silver ions "Argiform", saline solution
- Keywords
- intra-articular, polyacrylamide hydrogel, PAAG, Hydrous biopolymer with silver ions "Argiform" (HBISA), NOLTREX
- Medical subject headings
- Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydrous biopolymer with silver ions "Argiform"Device
Also called polyacrylamide hydrogel with silver ions, Synovial fluid endoprosthesis NOLTREX™
2 once-weekly intra-articular injections of NOLTREX™ 4.0 ml
saline solutionDevice
2 once-weekly intra-articular injections of saline solution 4 ml
| Study group | Role | What they receive |
|---|---|---|
| NOLTREX™, OA grade II-III | Experimental | 72 patients with gonarthrosis grade II-III were randomised to receive PAHG Receives: Device: hydrous biopolymer with silver ions "Argiform" |
| Placebo,OA grade II-III | Placebo comparator | 72 patients with gonarthrosis grade II-III were randomised to receive saline solution Receives: Device: saline solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of the Total WOMAC Score (WOMAC-T)
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.
Measured: baseline (week 1), week 25
Secondary outcomes (9)
Change of the Total WOMAC Score (WOMAC-T)
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.
Measured: baseline (week 1), week 13 (visit 4)
The Pain Subscale Score WOMAC-A Changes
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.
Measured: 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
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.
Measured: baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
Patient Assessment of Treatment Efficacy
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).
Measured: Week 6, Week 13 and Week 25
Investigator Assessment of Treatment Efficacy
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).
Measured: Week 6, Week 13 and Week 25
Assessment of the Total Number of NSAID Tablets Taken
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.
Measured: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
Assessment of the Total Number of Paracetamol Tablets Taken
A patient diary was used to capture data about the number of paracetamol tablets taken.
Measured: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
Patient Exclusion Rates Due to Safety
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
Measured: Week 25
Exclusion Rate Due to Poor Patient Compliance
According to the protocol the reasons for patients drop-out included major protocol deviations (poor compliance) and withdrawal of informed consent.
Measured: Week 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2019
- Study start29 Nov 2019
- Primary completion2 Jun 2020
- Study completion17 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- multicenter double-blind randomized comparative placebo-controlled
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research Centre BIOFORM
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vladimir V Popov, DSc, Principal investigator, Non-budgetary HCF "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03897686
- Sponsor's protocol ID
- IA/PAAG-SI/OA/2019
- Status last verified
- Nov 2024
- First submitted
- 26 Mar 2019
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Double-blind Randomized Comparative Placebo-controlled Study of Efficacy and Safety of Intra-articular HBISA Endoprosthesis of Synovial Fluid (NOLTREX™) in Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT03897686
- Acronym / sponsor ID
- IA/PAAG-SI/OA/2019
- Conditions
- Osteoarthritis
- Keywords
- intra-articular, polyacrylamide hydrogel, PAAG, Hydrous biopolymer with silver ions "Argiform" (HBISA), NOLTREX
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Research Centre BIOFORMIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2019 (actual)
- Primary completion
- 2 Jun 2020 (actual)
- Study completion
- 17 Dec 2020 (actual)
- First posted
- 1 Apr 2019 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- multicenter double-blind randomized comparative placebo-controlled
| Arm | Type | Receives |
|---|---|---|
| NOLTREX™, OA grade II-III | Experimental | Device: hydrous biopolymer with silver ions "Argiform"72 patients with gonarthrosis grade II-III were randomised to receive PAHG |
| Placebo,OA grade II-III | Placebo comparator | Device: saline solution72 patients with gonarthrosis grade II-III were randomised to receive saline solution |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (34 listed)
- 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);
- Severe degenerative changes in the target knee joint determined as the joint space narrowing less than 2 mm;
- Varus or valgus deformation of the target knee joint;
- Instability of the target knee joint;
- Active inflammation of the target knee joint (edema, hyperemia, present effusion) at the study entry;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| hydrous biopolymer with silver ions "Argiform"Also: polyacrylamide hydrogel with silver ions, Synovial fluid endoprosthesis NOLTREX™2 once-weekly intra-articular injections of NOLTREX™ 4.0 ml | Device | NOLTREX™, OA grade II-III |
| saline solution2 once-weekly intra-articular injections of saline solution 4 ml | Device | Placebo,OA grade II-III |
Primary outcome
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.
9 secondary outcomes
Change of the Total WOMAC Score (WOMAC-T)
Time frame: 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)
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)
Patient Assessment of Treatment Efficacy
Time frame: Week 6, Week 13 and Week 25
Investigator Assessment of Treatment Efficacy
Time frame: 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)
Assessment of the Total Number of Paracetamol Tablets Taken
Time frame: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
Patient Exclusion Rates Due to Safety
Time frame: Week 25
Exclusion Rate Due to Poor Patient Compliance
Time frame: Week 25
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vladimir V Popov, DSc principal investigator
Non-budgetary HCF "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing hydrous biopolymer with silver ions "Argiform" and saline solution in people with Osteoarthritis, run by Research Centre BIOFORM at 4 sites in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of the Total WOMAC Score (WOMAC-T) (time frame: baseline (week 1), week 25). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.