Clinical trial NCT03897686: Intra-articular Polyacrylamide Hydrogel in Knee Osteoarthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteoarthritis
Keywords: intra-articular
polyacrylamide hydrogel
PAAG
Hydrous biopolymer with silver ions "Argiform" (HBISA)
NOLTREX
Lead sponsor: Research Centre BIOFORM
Sponsor class: INDUSTRY
First posted: 2019-04-01
Enrollment: 144
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: multicenter double-blind randomized comparative placebo-controlled
Primary purpose: TREATMENT

Brief 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

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 .

Eligibility criteria: 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.

Primary outcomes:
measure: Change of the Total WOMAC Score (WOMAC-T)
timeFrame: baseline (week 1), week 25
Secondary outcomes:
measure: Change of the Total WOMAC Score (WOMAC-T)
timeFrame: baseline (week 1), week 13 (visit 4)
measure: The Pain Subscale Score WOMAC-A Changes
timeFrame: baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
measure: The Stiffness (WOMAC-B) and Functionality (WOMAC-C) Subscale Scores Changes
timeFrame: baseline (week 1), week 6 (visit 3), 13 (visit 4) and 25 (visit 5)
measure: Patient Assessment of Treatment Efficacy
timeFrame: Week 6, Week 13 and Week 25
measure: Investigator Assessment of Treatment Efficacy
timeFrame: Week 6, Week 13 and Week 25
measure: Assessment of the Total Number of NSAID Tablets Taken
timeFrame: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
measure: Assessment of the Total Number of Paracetamol Tablets Taken
timeFrame: week 6 (visit 3), week 13 (visit 4), week 25 (visit 5)
measure: Patient Exclusion Rates Due to Safety
timeFrame: Week 25
measure: Exclusion Rate Due to Poor Patient Compliance
timeFrame: Week 25
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Non-budgetary healthcare facility "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
city: Omsk
country: Russian Federation
facility: "Clinical Diagnostic Center "Ultramed", LLC
city: Saint Petersburg
country: Russian Federation
facility: Private Healthcare Facilty "Clinical hospital "RZHD-Medicina" of the city Saint-Petersburg
city: Yaroslavl
country: Russian Federation
facility: State budgetary healthcare facility of Yaroslavl Region "Clinical hospital №3"
Study officials:
affiliation: Non-budgetary HCF "Railway clinical hospital n.a. Semashko N.A. at Lublino, OJSC "Russian Railways"
name: Vladimir V Popov, DSc
role: PRINCIPAL_INVESTIGATOR
References: