Pilot, Prospective, Comparative Multicentric Study Evaluating the Effects on the Arthrosis Biomarkers, the Clinical Effectiveness, the Tolerance of an Intra-articular Injection of Hyaluronic Acid KARTILAGE CROSS Versus Placebo in Patients Suffering From Knee Osteoarthritis

NCT ID: NCT02951585

Last Updated: 2016-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-05-31

Study Completion Date

2014-10-31

Brief Summary

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Intra-articular hyaluronic acid injections, also known as viscosupplementation, are a treatment option for knee osteoarthritis that serves to restore the decreasing rheological properties of synovial fluid. KARTILAGE® CROSS is a visco-elastic gel of highly purified reticulated hyaluronic acid. It contains mannitol to provide an anti-oxidative action and to avoid hyaluronic acid depolymerization. Reticulation and mannitol increase the residency time of the product in the joint cavity then allowing a single injection in painful knee osteoarthritis patients.

The US food and drugs administration (FDA) and European medicine agency (EMA), have recently published guidelines recommending a higher level of integration of biomarkers in the development and testing of new drugs to advance decision-making on dosing, time and treatment effect, trial design, and risk/benefit analysis. Biomarkers can be used not only in the process of drug development, but also in the future in assessment of individual patient's response to treatment.

Several soluble biomarkers have been identified as potential candidates to predict or monitor the efficacy of intervention. Coll2-1, a degradation product of type II collagen, and Coll2-1NO2, a nitrated form of the Coll2-1 peptide have been studied in human osteoarthritis and entered the qualification process. Evidences demonstrated them to be pertinent and to be foresee as markers used for the diagnosis, the prognosis, the burden of disease and the monitoring of a treatment efficacy.

The aim of this study was to provide with the first kinetic data regarding biomarkers in painful knee osteoarthritis patients treated with a new reticulated hyaluronic acid. The effects of the treatment were compared to those of saline solution. The primary endpoint was a specific osteoarthritis biomarker, Coll2-1. The secondary endpoints were the effects of the treatment or placebo on other biomarkers of osteoarthritis, its clinical efficacy and tolerance

Detailed Description

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Conditions

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Knee Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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KARTILAGE CROSS

Kartilage® Cross (2.2 mL, 16 mg/g of hyaluronic acid)

Group Type EXPERIMENTAL

KARTILAGE CROSS

Intervention Type DEVICE

Intra-articular injection of Kartilage Cross

Placebo

Saline solution (2.2-2.5 mL, NaCl 9 mg/g)

Group Type PLACEBO_COMPARATOR

PLACEBO

Intervention Type DEVICE

Intra-articular injection of physiological serum (saline solution)

Interventions

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KARTILAGE CROSS

Intra-articular injection of Kartilage Cross

Intervention Type DEVICE

PLACEBO

Intra-articular injection of physiological serum (saline solution)

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Man or Women, aged from 45 to 80
* Presenting a symptomatic femoro-tibial knee osteoarthritis responding to clinical and radiologic ACR (American College of Rheumatology) criteria,
* Symptomatic since at least 6 months
* Mean global knee pain determined on Visual Analog Scale for the last 24 hours over 40 mm (without any NSAIDs or analgesics for more than 48 hours).
* Kellgren and Lawrence (K\&L) radiological stage must have been II or III on pictures lasted less than 12 months
* Requiring a treatment with hyaluronic acid after failure or intolerance to first line analgesics or NSAIDs
* Having signed an informed consent after receiving comprehensive information
* Capable to follow the study instructions
* Benefiting from health insurance.

Exclusion Criteria

Related to the osteoarthritis pathology:

* Significant clinical knee effusion
* Radiographical Kellgren and Lawrence grade I or IV
* Osteoarthritis secondary to a microcrystalline arthropathy: chondrocalcinosis previously known or defined by a calcium border on at least one tibiofemoral spacing, gout ...
* Isolated femoropatellar osteoarthritis
* Presence of another joint (other than the evaluated knee) affected by osteoarthritis (known and symptomatic): collateral knee, hip, hand, shoulder, ankle or foot
* Chondromatosis or villonodular synovitis of the knee
* Paget disease
* Recent trauma (\< 1 month) of the evaluated knee
* Pathologies interfering with the evaluation of osteoarthritis (microcrystalline inflammatory arthropathy, rheumatoid arthritis, radiculalgia in the lower limbs, arteritis. etc)
* Acute inflammatory osteoarthritis (Kofus ≥ 7)

Related to previous and concomitant treatments

* Corticosteroids injection in the last month before injection regardless the concerned joint
* Hyaluronan injection in the last 6 months before injection regardless the concerned joint
* Analgesics and NSAIDs intake during the last 48 hours before inclusion visit
* Change in the dosage of slow-acting drugs against arthrosis i.e. chondroitin, glucosamine, diacerein or avocado-soybean unsaponifiables in the last 3 months before inclusion or planned during study
* Arthroscopy or surgery in the target knee in the last 3 months before inclusion
* Oral corticotherapy

Related to associated pathologies

* Severe diseases (severe hepatic failure, renal failure, uncontrolled cardiovascular diseases….)
* Dermatological infection at the site of injection
* Anticoagulant treatment
* Risk of hemorrhage according to the evaluator or injector assessment

Related to the patients

* Known allergy to hyaluronan
* Known allergy to acetaminophen
* Known allergy to mannitol
* Pregnant or breastfeeding women
* Premenopausal women without contraception
* Patient unable to read, and to write
* Patient having participated in a clinical research investigation in the last 3 months
* Patient under guardianship or judicial protection
Minimum Eligible Age

45 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Artialis

INDUSTRY

Sponsor Role collaborator

Laboratoires Vivacy

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

References

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Henrotin Y, Berenbaum F, Chevalier X, Marty M, Richette P, Rannou F. Reduction of the Serum Levels of a Specific Biomarker of Cartilage Degradation (Coll2-1) by Hyaluronic Acid (KARTILAGE(R) CROSS) Compared to Placebo in Painful Knee Osteoarthritis Patients: the EPIKART Study, a Pilot Prospective Comparative Randomized Double Blind Trial. BMC Musculoskelet Disord. 2017 May 26;18(1):222. doi: 10.1186/s12891-017-1585-2.

Reference Type DERIVED
PMID: 28549430 (View on PubMed)

Other Identifiers

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2012-A01521-42

Identifier Type: -

Identifier Source: org_study_id