noltrex isnoltrex is aa new generation new generation ooff ... · noltrex isnoltrex is aa new...

Noltrex isNoltrex is a a new generation new generation of of injection injection materials for osteoarthrosis treatmentmaterials for osteoarthrosis treatment

Hyaluronic products (HA)Hyaluronic products (HA)are effective only at early grade

of disease and have a short-term effectterm effect

Not proved:�HA injected into the joint does really efficiently restore

a homeostasis into destructing cartilage

Effect of HA products on a joint affected by ОА

a homeostasis into destructing cartilage�HA stimulates chondrocyte hyaluronan synthesis

sufficient for replacement of the synovia

Unknown:� the true term of presence of the injected HA in a joint

How long can a “system” with exhausted mechanisms of regulation of cell proliferation and

function be stimulated?

Cochrane Stroke Review Groupon-line source in evidence-based medicine

� injections of HA products are probably effective only for 13 weeks� injections of HA products are probably effective only for 13 weeks

� HA-product intra-articular injections, oral chondroprotectors, arthroscopic lavage or

debridement showed uneven clinical effectiveness (according to AHRQ Department

of Health and Human Services, USA)

� in USA and some EU countries viscosupplementation technique using HA-

preparations was excluded from the list of medical services paid by the insurance

companies as having no statistically proven effectiveness

”Development of new approaches to prevention and treatment of OA should have

a high priority” [David J. Samson, 2007]

Obtaining the manufacture design of water-containing

biopolymer with Ag++

1980s,

USSR

Creation of the hydrogel as a depot for prolonged release of therapeutic agents (drugs).

1992,

Kiev,

Obtained the first hydrogel-based product for plastic surgery. Currently this product is manufacturing by the swedish company Contura (Concern Ferrosan) under the trademark Aquamid™.

Ukraine(Concern Ferrosan) under the trademark Aquamid™.

1999 A technology of obtaining a hydrogel with the antibacterial activity was developed.

2001 NOLTREX™, endoprosthesis of synovial fluid was manufactured.

2007 NOLTREX™ was authorized for use in the European Union.

Material-biopolymer water-containing

with silver ions

NOLTREX™ molecular weight >

10 000 000 Dalton

3-Dimentional polyacrylamide 4,5 ± 1,5 %

Purified water 95,5 ± 1,5 %

Silver ions 0.01 ÷ 0,02 %

NOLTREX™ is the only hydrogel product hydrogel product

for endoprostheticsof synovial fluid

NOLTREX principle of action

• acting as viscoprosthesis for a longer period of time

• complete regain of viscous properties of synovial fluid

• mechanical stabilization of joint structures due to high density

of the material

• biochemical "protection" of joint tissues by binding

inflammatory mediators

• suppression of the bacterial infection manifestation within the • suppression of the bacterial infection manifestation within the

joint

• synovia substitution with 3-dimentional biopolymer bounded

with tissue fluid

Shear viscosity testNOLTREX vs. synovial fluid

NOLTREX physical properties are

identical to the natural properties identical to the natural properties

of the synovial fluid

of an intact joint

Study methodStudy method Regulatory actsRegulatory acts Brief description of testsBrief description of tests ResultsResults

Chemical stability State Standard (GOST) R ISO

10993.12-99(EN 30993-12-1994)

Determining the pH value, content of dryresidue, refraction index

Parameters are within reference intervals, the substance is chemically stable.

Monomer content testing

Standard (GOST) R ISO10993.9-99

The content of acrylamide was determinedby meansof chromatography

The monomer content does not exceed the maximum permissible

NOLTREX pre-clinical trials

testing 10993.9-99(EN 30993-9-1994),

Standard (GOST) R ISO10993.12-99,


by meansof chromatography exceed the maximum permissible value.

Content of metals testing


(EN 30993-15-1994)

The content was determined by means oflaser spectrometry using the measuringdevice “EMAL-2”

The metal content does not exceed the maximum permissible value.

Antibacterial activity “Guidelines on experimental (preclinical) trials

of new pharmacological substances”, 2000

The following strains were used in the tests:1.Staphylococcus aureusАТСС 25 923.2.Staphylococcus aureus АТСС 43300

The material possesses anantibacterial effect.

substances”, 20002.Staphylococcus aureus АТСС 43300 MRSA.3.Escherichia coli АТСС 25922.4. Pseudomonas aeruginosaАТСС 27853.

Cytotoxic action testing


(EN 30993-5-1994)

Cytotoxicity was studied on PC12 cell line(Rat adrenal pheochromocytoma) usingMTT-test.

Not cytotoxic.

Acute toxicity testing Standard (GOST) R ISO10993.11-99

(EN 30993-11-1994),Supplements B, B1

Acute toxicity was studied on albino miceby intra-abdominal administration of thematerial.

Administration at a dose of 50ml/kg of body weight of animalsdid not lead to either death of miceor clinical signs of intoxication.

Study methodStudy method Regulatory actsRegulatory acts Brief description of testsBrief description of tests ResultsResults

Subchronic toxicity test Standard (GOST) R ISO10993.11-99

(EN 30993-11-1994)

Subchronic toxicity was studied on albino ratsby subcutaneous administration.

During 2,5 months no general toxiceffect of the material was revealed.

Chronic toxicity test Standard (GOST) R ISO10993.11-99

(EN 30993-11-1994)

Chronic toxicity was studied on dogs bysubcutaneous administration.

During 1,8 months no toxic effectwas revealed.

Haemolytic action test Standard (GOST) R ISOIn vitro studyof haemolyticactionof material The extracts from all samples

NOLTREX pre-clinical trials

Haemolytic action test Standard (GOST) R ISO10993.4-1999

(EN 30993-4-1994),Supplement B

In vitro studyof haemolyticactionof materialextract was studied on isolated rabbiterythrocytes.

The extracts from all samplesshowed no haemolytic activity.

Sensitizing action test Standard (GOST) R ISO10993.10-99

(EN 30993-10-1994),Supplement E

The study on albino rats was carried out usingimmunological reaction of mast cellsdegranulation.

No sensitizing action of the materialwas revealed.

Mutagenic action Standard (GOST) R ISO10993.3-99

(EN 30993-3-1994)

There have used the micronuclear test ofpreparations of the femoral bone marrow ofalbino mice.

The material exerted no mutagenicactivity.

Gonadotoxicity Standard (GOST) R ISOThe gonadotropicaction was assessed by the No abnormal deviations of theGonadotoxicity Standard (GOST) R ISO10993.3-99

(EN 30993-10-1994)

The gonadotropicaction was assessed by the condition of testicles in histologic analysis of reproduction organs in male rats.

No abnormal deviations of thegonadal structure was revealed.

Pathomorphologicalstudy of visceral organs


(EN 30993-3-1994)

The morphological study of organs wascarried out in a subchronic experiment onalbino rats and chronic experiment on dogs.

No alterations in histologicallyexamined structure of visceral organswere revealed.

Implantation test Standard (GOST) R ISO10993.6-99

(EN 30993-6-1994)

The histological study of the implantation area was carried out in rats, rabbits, and dogs.

Minor tissue reaction and highdegree of the biomaterialcompatibility were observed.

Antibacterial properties of NOLTREX

Bacterial growth in the zone of the well containing the material “Formacryl” (the left well [1] on figures) does

not differ from the surrounding bacterial growth.

The well containing the material “Argiform” (NOLTREX) (the right well [2] on figures) shows zones of growth

inhibition on the Petri dishes with each control culture.

Staphylococcus aureus ATCC 25923 Staphylococcus aureus ATCC 43300

inhibition on the Petri dishes with each control culture.

Bacteria strains used in test

S. aureus25923

(MSSA)

S. aureus43300

(MRSA)

E. coli25922

P. aeruginosa27853

1

2

Bacteriostasis zone, in mm 4,0 3,0 3,0 5,0

Implantation test No 1

Laboratory of Pathomorphology, I.M. Sechenov Moscow Medical Academy, Moscow, RussiaMoscow, Russia

Study of NOLTREX effect

on the knee joint structures

was performed on 20 outbred rabbits

Left jumping joint: 1 ml of Noltrex was injected

Right jumping joint: remained intact (control)

Terms of withdrawal from the experiment: Day 1,3,7,10,14 and Month 1,3,6,12 и 18 after injection

Condition of the synovial membrane of the experimental animals during study

Day 7Day 14 Day 30

Day 3

6th month of the experiment

Day 1

Control (intact)joint

Condition of the hyaline cartilage of the experimental animals during study

Day 7

Infrared spectrum of NOLTREX samples

11

6th month of the experiment

11

22

Control (intact)joint

11 – original sample22 – retrieved from the joint of experimental animal after 6 months

Implantation test No 1. Conclusions:

1. Intra-articular injections of NOLTREX even in large amounts do not lead to

inflammation process in the synovium or degenerative processes in the cartilage.

2. Water in NOLTREX is replaced with native synovial fluid, forming a new compound

“polymer MATRIX filled in with synovial fluid” within the joint.

3. The gel forms complex substance with synovial fluid membrane without affecting

metabolism of joint tissues.

4. Prolonged and safe action of viscoprosthesis and its advantage over pharmaceutical

viscosupplementing agents are ensured by absence in macroorganism of ferments

decomposing polymer links.

� prolonged presence into the joint cavity

Main advantages of NOLTREX

� high-degree biocompatibility

� causes neither allergic reactions (100% synthetic material)

� bactericidal activity

� high viscosity

� renewal of the volume and viscosity of own synovial fluid

� improvement of consistence and composition of synovial fluid

� protection of the synovial cartilage from destruction, isolation of the articular

surfaces

Implantation test No 2Animal Anatomy and Histology Department, K.I. Skryabin Moscow State Academy of

Veterinary Medicine and Biotechnology, Moscow, Russia

Study of NOLTREX effect

on the repairing chondrogenesis by induced gonarthrosis

was performed on 27 outbred rats

Left knee joint: the hyaline cartilage wedge-shaped defect of the femoral epiphysisLeft knee joint: the hyaline cartilage wedge-shaped defect of the femoral epiphysis

Right joint: intact

Study group: injection of 0,2–0,3 ml of Noltrex

Control group: injection of 0,2–0,3 ml of normal saline solution

Terms of withdrawal from the study: day 0, 14, 30 of the experiment

Condition of the hyaline cartilage, day 14

Condition of the hyaline cartilage, day 30

Control group Control group

Joint cartilage structural changesby induced gonarthrosis

Experimental model of osteoarthrosis, Day 0

Group received NOLTREX Group received NoltrexGroup received NOLTREX Group received Noltrex

1. NOLTREX intended for substitution of synovial fluid compensates its lubricative

Implantation test No 2. Conclusions:

1. NOLTREX intended for substitution of synovial fluid compensates its lubricative

properties and optimizes a tribomechanical situation in the joint.

2. NOLTREX injected into the affected joint creates favourable microclimate providing

not only improvement of joint function but also accelerating the reparation

processes.

3. Restoration of the articular cartilage with organo-specific zonal differentiation and

appearance of the focuses of the osseochondral junction in the presence of

NOLTREX suggests restoration of the relationship between calcified zone of theNOLTREX suggests restoration of the relationship between calcified zone of the

articular cartilage and subchondral bone.

4. Intra-articular injection of “Noltrex” optimizes reparative chondro- and osteogenesis

at damaged tissue of the knee joint.

According to the data of the World Health Organization:

• 1 500 000 operations on endoprosthetics of joints are performed in the world annually

• purulent complications rate during endoprosthetic repair varies from 1.4% (Solvate, Chekovsky,

1982) to 12% (James Hunter, 1982; Cameron, 1982; Hugues, 1987; Zukerts et al., 1989; Klyuchevsky V.V., 1996;

Agadzhanyan V.V., 1996)

Clinical practice

Agadzhanyan V.V., 1996)

• NSAIDs intake complications: 70 000 hospitalizations and 7 000 lethal outcomes per year due to

peptic ulcers of the gastrointestinal tract in the USA

• gastrointestinal haemorrhages and ulcer perforations – 1-1.5 cases per 100 patients; clinically

significant gastroduodenal ulcers is encountered in 10 - 15% of patients using NSAIDs for a long

time

NOLTREX has Certificates of Conformity of the Russi an Federation, ISO, EU.

More than 280 000 injections of NOLTREX have been p erformed in the world.

More than a decade of safe use.

There have been no convincing evidences of any seri ous complications reported.

Clinical trialsStudiesStudies

(Medical institutions, authors, year)(Medical institutions, authors, year)PlanPlan N of N of

casescasesN of N of

injecinjec--tionstions

StudyStudydudu--

rationration

Results of the studiesResults of the studies

R.R. Vreden Russian Scientific Research Institute ofTraumatology & OrthopaedicsEmelyanov V.G., 2003

Phase I-II 10 3 6

Injections in patients with OA do not cause side effects, are well tolerated,sometimesa burningsensationoccursin the joint duringthe introductionof

Regional Scientific Research Clinical Institute n.a.M.F. Vladimirsky (MRSRCI)Buachidze O.Sh., Zar V.V., 2003

Phase I-II 32 3 6,5

Moscow Regional Hospital for War Veterans(MRHWV)

Phase I-II 18 3 6

MC – Multicentre studies, R – Randomized studies,

NC – Noncontrolled (open) studies, C - Controlled studies

sometimesa burningsensationoccursin the joint duringthe introductionofthe material. Injections bring long lasting relief or disappearance ofpain, aswell as relief of dysfunction in the joint for about 6 months.

(MRHWV)Martynov D.V., 2003

I-II 18 3 6

Peoples’ Friendship University of Russia (PFUR)(Municipal Clinical Hospital No 13, Municipal ClinicalHospital No 31)Zagorodniy N.V., 2003

Phase I-II

30 3 6,5

Ukrainian Medical Stomatological Academy (Ukraine,Poltava)Mokhnachyov O.V., Pelipenko V.P., 2007

Phase I-II 67 3 7

MRSRCIBuachidze O.Sh., Zar V.V., Tarek M., 2004

Phase I-II 50 3 18,5

In 90% of patients with OA the effect lasts for 6 month. Efficiency after6month and 18,5 month was in 88-95% and 67-85% cases respectively.

Municipal Clinical Hospital No 59Parakhin Yu.V., Popov F.V., Myakusheva T.N., 2009

Phase IIaNC

38 3-4 755% showed positive result after 2 injections, 26% after 3-4 injections.Prolonged effect for up to 6 month was observed in 76,3% of patients.

MRSRCI, PFUR, MRHWV Phase 80% of patients with OA are satisfied with the treatment,92% rate itMRSRCI, PFUR, MRHWVZagorodniy N.V., Zar V.V., 2006

Phase IIa

MC, NC

408 3 26

80% of patients with OA are satisfied with the treatment,92% rate itpositively. The synovitis occurred only in 0,5%, arthralgia – in 9,3% ofcases. The duration of the effect depends upon the stage of OA (from 6 to 12months).

Clinical Training Centre of the Semey State Medical Academy (Kazakhstan, Semey)Ivanova R.L., Agibaeva Zh.B., 2007

Phase IIb

R, C 150 3 1,5

The patients with RA and OA received the following treatment: Xefocam,Ambene, Diprospan, “Noltrex”, control (a standard oral anti-inflammatorycourse). “Noltrex” provides local clinical response without systemic effects,other than those associated with the reduction of inflammation in the joint.

PFUR (MCH No 13, MCH No 31), MCH No 12Zagorodniy N.V., Karpovich N.I., 2010

Phase IIa

R, C60 5 9

Control – NSAID intake. By the end of the study group "Noltrex + NSAID"vs. control, the last is higher in pain and lower in patient functional activityparameters.

MRSRCI, MRHWV, Domodedovo Central DistrictHospital, Dzerzhinsky CDH, Ivanteevka CDHZar V.V., Voloshin V.P., Martynov D.V., 2011

Phase IIb

MC, NC

186 1 6

"Noltrex" showed a tardive effect at 6 weeks. At 24 weeks after injection,the effect is not weakened and fixed.

Phase IIa noncontrolled (open) study Municipal Clinical Hospital No 59

(Parakhin Yu.V., Popov F.V., Myakusheva T.N., 2009)

� 38 patients with arthrosis aged 48 ± 83 years� gonarthrosis evaluated in 35 cases (92%),

talocrural arthrosis in 3 cases (8%)

� each patient underwent according to the procedure:• 3-4 weekly injections of 2,5 ml of NOLTREX• all injections were performed under local anaesthesia

� 17 patients (45%) noticed some slight discomfort during the 1st 24 hours after the injection

� therapeutic effect manifested by pain decrease and improvementof joint mobility

� distant results were assessed usingVAS and WOMAC

Conclusions:

Phase IIa noncontrolled (open) study Municipal Clinical Hospital No 59

(Parakhin Yu.V., Popov F.V., Myakusheva T.N., 2009)

� Efficacy of NOLTREX is manifested by the lack of pain syndrome, a decrease in joint

stiffness and increase of the amplitude of movements in the joints (the endoprosthesis

is effective in 76.3% of cases).

� The material is highly effective in complex treatment of deforming gonarthrosis and

talocrural arthrosis.

� The endoprosthesis NOLTREX may be employed in a local conservative treatment of

degenerative-dystrophic diseases of large joints.

� NOLTREX may be used in case of no indications for surgery or in cases of presence

of absolute and relative contraindications to operative treatment.

� The complex course of conservative treatment for OA includes anti-inflammatory

therapy, improvement of microcirculation and regional blood flow, vitamin therapy,

exercises, massage, physiotherapy and may include NOLTREX IA-injections.

Phase IIa noncontrolled (open) study MRSRCI, PFUR, MRHWV (Zagorodniy N.V., Zar V.V., 2006 )

• 527 patients with gonarthrosis

aged 57,2 ± 7,3 years

• 408 patients completed the study

(119 withdrawn)

• all patients received 3 injection

of NOLTREX 2,5ml each

with 6-7 day interval

Conclusions:

Phase IIa noncontrolled (open) study MRSRCI, PFUR, MRHWV (Zagorodniy N.V., Zar V.V., 2006 )

� The tolerability and safety of the material-biopolymer was demonstrated in 527

patients with OA.

� Significant benefits of NOLTREX application were achieved regardless of disease

stage.

� The duration of GA treatment effect was at least 52 week.

� The adverse events were observed in the form of arthralgia and causalgia in 16% of� The adverse events were observed in the form of arthralgia and causalgia in 16% of

cases, synovitis after the gel introduction was revealed in 2 patients (0,5%).

� Long-term efficacy of NOLTREX was proved, with neither local nor general iatrogenic

complications peculiar to pharmaceutical agents intended for local (intra-articular)

injections.

� 76 patients with gonarthrosis aged 55,3±3,1 years

� the average duration of the disease is 6,8+3,2 years

� assessment on 0, 1, 7 and 30 day after injections course

Phase IIb controlled study Clinical Training Centre of the Semey State Medical Academy (Kazakhstan, Semey)

(Ivanova R.L., Agibaeva Zh.B., 2007 )

and after the 3rd injection of NOLTREX respectively

� all patients completed the study

� treatment method: effusion has to be evacuated if

it’s present following Xefocam or Diprospan

introduction, then after 1-3 days 3 weekly NOLTREX

injections performed

� NOLTREX group was compared with groups 1-3 by the f ollowing measures:

- pain level on the VAS scale (0÷10, where 10 = maximum possible pain level),

- index of swelling in points (0÷4, where 4 = maximum possible swelling),

- joint mobility – the angles both of maximum flexion and extension in degrees,

- maximum walking speed measured in a 30-meter walk test in seconds,

- GAG level in the blood serum according to Karyakina’s method, in absorbance units,

- Erythrocyte Sedimentation Rate (ESR) in mm/h



Group 1 – XEFOCAMXEFOCAM

Group 2 – AMBENEAMBENE

Group 3 – DIPROSPANDIPROSPAN

Group 4 – Diprospan + NOLTREXNOLTREX

Dynamics of algofunctional parameters:

«VAS», «SI», «maximum walking speed measured

in a 30-meter walk test», «knee joint mobility»

at patients with OA in different groups

depends of study terms


Group 5 – Control (standard antiControl (standard anti--

inflammatory peroral course)inflammatory peroral course)

Maximum extension angle, in degrees

Maximum flexion angle, in degrees

Group 1 – XEFOCAMXEFOCAM

Group 2 – AMBENEAMBENE

Group 3 – DIPROSPANDIPROSPAN




Group 5 – Control (standard antiControl (standard anti--

inflammatory peroral course)inflammatory peroral course)

Dynamics of laboratory parameters

«serum GAG level» and «ESR»

in patients with OA in different groups

depending of the study term

Conclusions:



� The tolerability and safety of the material-biopolymer was demonstrated in 20 patients with

OA.

� The application of NOLTREX in the absence of active synovitis allows to improve joints

function.

� NOLTREX provided a significant improvement in clinical parameters, as well as pronounced

local clinical response with no systemic effects except for signs connected with an inflammation

decrease.

� NOLTREX offers no influence at ESR result but significantly reduces GAG levels, which reflects� NOLTREX offers no influence at ESR result but significantly reduces GAG levels, which reflects

its direct effect on reducing the destruction of articular cartilage.

� Systemic anti-inflammatory effect is more pronounced when using Diprospan.

� Application of NOLTREX is recommended at patients with OA in combination with Diprospan

or Xefocam, providing improvement of functional condition, systemic inflammatory relief and

protection of hyaline cartilage.

Phase IIb noncontrolled (open) study MRSRCI, MRHWV, Central District Hospital of Domodedovo, CDH of Dzerzhinsky, CDH of Ivanteevka

(Zar V.V., Voloshin V.P., Martynov D.V., 2011)

Phase II multicentre prospective open clinical trial

Medical institutions Moscow Regional Research Clinical Institute n.a. M.F. Vladimirskiy, Moscow Regional Hospital for War Veterans, Domodedovo Central District Hospital, Dzerzhinsky CDH,

Determining of clinical efficacy of a single NOLTRE X injection

Hospital for War Veterans, Domodedovo Central District Hospital, Dzerzhinsky CDH, Ivanteevka CDH

Materials Patients of both sexes aged 43 to 89 years with one- or two-sided gonarthrosis

Method The gel was injected into the superior recess of the knee joint in an amount of 5 ml at a time

Follow-up visit terms 0, 1, 6 и 24 weeks after material injection

Data collection Lequesne questionnaire

Results assessment Statistical analysis using the SPSS 13.0 package

Inclusion criteria Exclusion criteriaInclusion criteria Exclusion criteria

1. Clinical evidence of idiopathic gonarthrosis.2. X-ray verified OA based on Kellgren & Lawrence grading system.3. OA symptoms in the affected knee joint for at least 1 year.

1. Secondary gonarthrosis (post-traumatic, post-inflammatory, rheumatoid arthritis, associated with skin diseases).2. Chronic active fibromyalgia. 3. Metabolic arthritis. 4. Hyaluronic acid injections into the study knee within 6 months before the screening visit.5. Corticosteroid IA-injections or debridement to the study knee within 3 months before the screening visit.6. NSAIDs course intake.

• 236 patients with gonarthrosis

aged 65,3 ± 11,56 years

• 186 patients with uni- and bilaterial

GA completed the study

• the ratio of II:III:IV grades in men



and women was as follows

5,8:6,2:1 and 4,9:4,1:1 respectively

• treatment method

1) 5,0 ml of Noltrex as a single injection;

2) material injection into the joint

- 1 injection in unilateral case,

- 1 injection into each joint simultaneously

in bilateral case

Assessment according to Lequesne questionnaire (Zar V.V., Voloshin V.P., Martynov D.V., 2011)

Index Index Score Score NyctalgiaAbsentOnly on movement or in certain positionsEven at rest

012

Morning stiffness or pain after risingAbsentLasts less than 15 minutes15 minutes and more

012

Increase of pain while standing for 30 minutesNo increase of painPain increases (also mark if long standing is impossible)

01

Do you experience a joint pain while walking?No painexperiencedwhile walking 0

Grade II

GradeIII

GradeIV

FigureM ± σ (p = 0.05)

Day 0 12.6 ±2.39

19.9 ±3.39

24.1 ±1.46

Dynamics of the total Lequesne’s index

No painexperiencedwhile walkingPain appears only after walking on certain distancesPain appears from the very beginning and then increases

012

Pain or discomfort while standing up from the sitting positionAbsentPresent

01

Maximum walking distance without pain:More than 1 km, but with restApproximately 1 kmFrom 500 to 900 mFrom 300 to 500 mFrom 100 to 300 mLess than 100 m

123456

Do you walk using auxiliary devices?I do not use walking aidI useone walking stick (cane) or one crutchI use two walking sticks, two crutches or go-carts

+0+1+2

Difficulties in daily living:Are you able to go up one flight of stairs?Without difficultyWith difficultiesUnable

012

Week 1 10.1 ±3.25

16.1 ±3.25

19.9 ±3.26

Week 6 6.1 ±1.97

12.9 ±3.59

16.2 ±1.67

Unable 2

Are you able to go down one flight of stairs?Without difficultyWith difficultiesUnable

012

Are you able to put anything on the lower shelf of a cupboard standing onyour knees?Without difficultyWith difficultiesUnable

012

Are you able to walk on an uneven road?Without difficultyWith difficultiesUnable

012

Do you ever experience fulgurant pain or a sudden sensation of loosingsupport in the affected extremity?NeverSometimesOften

012

1.97 3.59 1.67

Week 24 3.5 ±1.48

11.4 ±3.61

14.8 ±2.15

Day 0 Week 1



Dynamics of intensity of «night pain in joint » parameter

Week 6 Week 24

Day 0 Week 1



Dynamics of intensity of «morning stiffness » parameter

Week 6 Week 24

Day 0 Week 1



Dynamics of intensity of «maximum walking distance » parameter

Week 6 Week 24

Day 0 Week 1

Dynamics of intensity of «walk with cane/crutch » parameter



Week 6 Week 24

Statistical analysis of the data concerning the total Lequesne’s index in the groups

ANOVA

(Post Hoc Bonferroni)



(Post Hoc Bonferroni)

F 173,848÷243,713

n = 186; p < 0,001

CORRELATION

Strong positive:

• GA grade < = > Index• GA grade < = > Index

• Patient’s age < = > Index

Weak positive:

• Number of joints < = > Index

Conclusions:

� IA-application of NOLTREX showed no development of either side effects or



complications in 186 patients.

� The injection is followed by rapid (within 1-6 weeks) improvement of the patient’s

physical activity; pain syndrome is decreased or stopped, significantly improving the

patient’s quality of life.

� During study 23 patients abandoned their additional walking devices (cane or

crutches).

� 24 weeks after injection the effect of NOLTREX is not only unflagging, but in most

cases is fixed or becomes slightly more pronounced.

� As a result of its prolonged functioning the isometric and dynamic capabilities of the

lower limbs are improved due to unload of joints and muscles compensating lack of

function

NOLTREX INTRODUCTION TECHNIQUE

Viscoprosthesis NOLTREX in orthopaedic practice

� NOLTREX does not include hyaluronic acid

� NOLTREX is the only polymeric hydrogel endoprosthesis of synovial fluid with

silver ions

� NOLTREX is safe, biocompatible, and antibacterial� NOLTREX is safe, biocompatible, and antibacterial

� more than 280 000 injections performed

� pronounced clinical effect of treatment is observed from 6 months to 2 years and

expressed in OA main symptoms relief

� 90% of patients repeated their NOLTREX IA-treatment in some time after the 1st

course, since they have been satisfied with the results

Thank you for your attentionThank you for your attention!!

noltrex isnoltrex is aa new generation new generation ooff ... · noltrex isnoltrex is aa new...

Documents