Knee OsteoarthritisEPIKARTNCT02951585
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
A study testing KARTILAGE CROSS in people with Knee Osteoarthritis, run by Laboratoires Vivacy.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- KARTILAGE CROSS
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- No sites listed yet
- Study dates
- May 2013to Oct 2014
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Having signed an informed consent after receiving comprehensive information
- Capable to follow the study instructions
- Benefiting from health insurance.
Who cannot join
- 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
Show all 32Show fewer
- 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
About this study
Official title: 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.
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.
Read more
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
- Conditions
- Knee Osteoarthritis
- Being tested
- KARTILAGE CROSS, PLACEBO
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KARTILAGE CROSSDevice
Intra-articular injection of Kartilage Cross
PLACEBODevice
Intra-articular injection of physiological serum (saline solution)
| Study group | Role | What they receive |
|---|---|---|
| KARTILAGE CROSS | Experimental | Kartilage® Cross (2.2 mL, 16 mg/g of hyaluronic acid) Receives: Device: KARTILAGE CROSS |
| Placebo | Placebo comparator | Saline solution (2.2-2.5 mL, NaCl 9 mg/g) Receives: Device: PLACEBO |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patient with a reduction of at least 10 nmol/l of serum Coll2-1 between inclusion visit (10 days before injection) and 3 months after injection.
Measured: 3 months after injection
Secondary outcomes (7)
Variation in Coll2-1 between inclusion and 1 month or 6 months;
Measured: 1 month and 6 months
Variation of Lequesne index (LI) between inclusion visit and further visits
Measured: 1 month, 3 months and 6 months
Variation in the global assessment of pain with visual analog scale (0-100 mm) between inclusion visit and further visits,
Measured: 1 month, 3 months and 6 months
Percentage of responders according to OMERACT/OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) at 3 months and 6 months
Measured: 3 months and 6 months
Acetaminophen and Nonsteroidal anti-inflammatory drugs (NSAID) consumption during the study
Measured: 1 month, 3 months and 6 months
Patient's global assessment of the disease activity
Measured: 1 month, 3 months and 6 months
Monitoring of adverse events
Measured: 1 month, 3 months and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Nov 2016 (estimated)
- Study startMay 2013
- Primary completionSep 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Knee 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
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laboratoires Vivacy
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Artialis
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02951585
- Sponsor's protocol ID
- 2012-A01521-42
- Acronym
- EPIKART
- Status last verified
- Oct 2016
- First submitted
- 28 Oct 2016
- Last updated
- 1 Nov 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 28549430
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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.
- ClinicalTrials.gov ID
- NCT02951585
- Acronym / sponsor ID
- EPIKART / 2012-A01521-42
- Conditions
- Knee Osteoarthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Laboratoires VivacyIndustry (pharma, biotech, devices)
- Collaborators
- Artialis
- Study start
- May 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 1 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| KARTILAGE CROSS | Experimental | Device: KARTILAGE CROSSKartilage® Cross (2.2 mL, 16 mg/g of hyaluronic acid) |
| Placebo | Placebo comparator | Device: PLACEBOSaline solution (2.2-2.5 mL, NaCl 9 mg/g) |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (32 listed)
- 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
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 |
|---|---|---|
| KARTILAGE CROSSIntra-articular injection of Kartilage Cross | Device | KARTILAGE CROSS |
| PLACEBOIntra-articular injection of physiological serum (saline solution) | Device | Placebo |
Primary outcome
Percentage of patient with a reduction of at least 10 nmol/l of serum Coll2-1 between inclusion visit (10 days before injection) and 3 months after injection.
Time frame: 3 months after injection
7 secondary outcomes
Variation in Coll2-1 between inclusion and 1 month or 6 months;
Time frame: 1 month and 6 months
Variation of Lequesne index (LI) between inclusion visit and further visits
Time frame: 1 month, 3 months and 6 months
Variation in the global assessment of pain with visual analog scale (0-100 mm) between inclusion visit and further visits,
Time frame: 1 month, 3 months and 6 months
Percentage of responders according to OMERACT/OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) at 3 months and 6 months
Time frame: 3 months and 6 months
Acetaminophen and Nonsteroidal anti-inflammatory drugs (NSAID) consumption during the study
Time frame: 1 month, 3 months and 6 months
Patient's global assessment of the disease activity
Time frame: 1 month, 3 months and 6 months
Monitoring of adverse events
Time frame: 1 month, 3 months and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2016.
- Derived from this study: PubMed 28549430Henrotin 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.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing KARTILAGE CROSS in people with Knee Osteoarthritis, run by Laboratoires Vivacy.
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 9 inclusion and 32 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 1 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Percentage of patient with a reduction of at least 10 nmol/l of serum Coll2-1 between inclusion visit (10 days before injection) and 3 months after injection. (time frame: 3 months after injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02951585, which also lists 1 linked publication.
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 1 Nov 2016.