Clinical trial NCT01791062: Safety and Efficacy Study of HYTOP® in the Treatment of Focal Chondral Defects.
Official title: Safety and Efficacy of a Novel, Cell-free Cartilage Repair Construct in the Treatment of Focal Chondral Defects Involving the Femoro-tibial Compartment of the Knee Joint.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Focal Chondral Defect in Femoro-tibial Compartment of the Knee Joint
Keywords: cartilage tissue engineering
hyaluronan
hyaluronic acid
Lead sponsor: TRB Chemedica AG
Sponsor class: INDUSTRY
First posted: 2013-02-13
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The two-layer bioresorbable HYTOP® matrix consists of an upper layer of highly purified porcine splint-skin which contains natural pores, and a lower layer of highly purified collagen fleece containing hyaluronan (HA).

In this study, the medical device will be used and evaluated in a one-step procedure combining microfracturing with surgical implantation of HYTOP®. HYTOP® will support haemostasis in the articular cartilage defect, act as a support for cell growth and as a three-dimensional scaffold for cell differentiation. HYTOP® will protect the underlying tissue after cartilage debridement and/or microfracturing of the subchondral bone.

The primary working hypothesis is that HYTOP® is safe and suitable as a cell-free matrix to support haemostasis, as a cover for the cartilage lesion and eventually to enhance cartilage regeneration in a one-step surgical procedure.


Eligibility criteria: Inclusion Criteria:

* Male and female patients between 18 and 50 years of age.
* Good general health condition.
* Signed written informed consent.
* General anaesthesia is justifiable for the patient from the medical point of view.
* Focal chondral defects involving the femorotibial compartment of the knee joint localised in only one compartment and not larger than the size of one HYTOP® patch.
* Isolated one-sided chondral lesion.
* Cartilage defect classified as Outerbridge grade 3 or 4.
* Chondral lesions not exceeding through the subchondral bone (intact subchondral bone).
* Nearly intact chondral structure surrounding the defect, specifically Outerbridge grade 2 or less.
* Corresponding joint area classified with maximum Outerbridge grade 2.
* Clinical symptoms in the target joint (pain on walking 100 m of more than 4 on an 11-point numerical scale or swelling or locking or 'giving way').
* Ensured compliance of subjects over the whole study period.

Exclusion Criteria:

* Treatment with any investigational product within 4 weeks prior to study entry.
* Patients with known hypersensitivity to the constituents of the product or any component or procedure used in the study.
* Patients with previous treatment of the study relevant defect site.
* Cartilage lesion is not intact shouldered, has bipolar or corresponding involvement or bipolar 'kissing' lesions.
* Necessity of cartilage repair treatment at bilateral joints.
* Patients with meniscus lesions, total or partial (more than 1/3 of total volume) resected meniscus, limited joint mobility, varus/valgus joint malalignment of more than 5 degrees or insufficient ligament support.
* Inflammatory joint diseases (e.g. rheumatoid arthritis, Bechterew disease, chondromatosis).
* Infection at study relevant site.
* Osteoarthritis, arthrofibrosis or haematopoetic related diseases.
* Study relevant metabolic disease, adipositas (BMI equal to or greater 30 kilogram per square meter).
* Study relevant neoplastic, neurological or mental illness.
* Study relevant autoimmune disease.
* Patients with elevated risk of bleeding.
* Recent history of drug and/or alcohol abuse (within the last 6 months).
* Pregnant or lactating females.
* Participants of childbearing age (pre-menopausal) who do not accept the use of methods of birth control with pearl index more than 1% (e.g. oral contraceptives, vaginal ring, hormone-releasing intrauterine device (IUD), implants, depot syringes, hormone patch, double barrier method, tubal ligation, vasectomised partner,...) during the treatment period and the first 12 weeks of follow-up period.
* Subjects unable to understand informed consent or having a high probability of non compliance to the study procedures and/or non completion of the study according to investigator's judgement (e.g. illiteracy, insufficient knowledge of local language).
* Subjects not capable of contracting and of understanding the nature, risks, significance and implications of the clinical investigation and unable to form a rational intention in the light of these facts.
* Low probability of compliance with after-care rehabilitation scheme.
* Forbidden concomitant treatment affecting the evaluation of study parameters (e.g. oral intake of chondroitin sulfate, glucosamine, piascledine, other i.a. treatments like depot corticosteroids or arthroscopic procedures).

Primary outcomes:
measure: Number of adverse events with causal relationship to the investigational medical device.
timeFrame: Up to 2 years (plus or minus 14 days) after surgery.
Secondary outcomes:
measure: All adverse events without causal relationship to the investigational medical device.
timeFrame: Up to 2 years (plus or minus 14 days) after surgery.
measure: Joint girth measurement
timeFrame: Baseline
measure: Joint girth measurement
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Joint girth measurement
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Joint girth measurement
timeFrame: On Day 5 after surgery.
measure: Pain intensity
timeFrame: Baseline
measure: Pain intensity
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Pain intensity
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Pain intensity
timeFrame: On Day 5 after surgery.
measure: Magnetic Resonance Imaging (MRI) Signal intensity
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: MRI Signal intensity
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Presence of lesions
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Presence of lesions
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone oedema
timeFrame: Baseline
measure: Presence of subchondral bone oedema
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone oedema
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone cyst
timeFrame: Baseline
measure: Presence of subchondral bone cyst
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone cyst
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Presence of effusion
timeFrame: Baseline
measure: Presence of effusion
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Presence of effusion
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Joint girth measurement
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Pain intensity
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: MRI Signal intensity
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Presence of lesions
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone oedema
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Presence of subchondral bone cyst
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Presence of effusion
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Knee injury and osteoarthritis outcome score (KOOS)
timeFrame: Baseline
measure: Knee injury and osteoarthritis outcome score (KOOS)
timeFrame: On Day 5 after surgery.
measure: Knee injury and osteoarthritis outcome score (KOOS)
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Knee injury and osteoarthritis outcome score (KOOS)
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Knee injury and osteoarthritis outcome score (KOOS)
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
measure: Subjective knee evaluation form
timeFrame: Baseline
measure: Subjective knee evaluation form
timeFrame: On Day 5 after surgery.
measure: Subjective knee evaluation form
timeFrame: On Day 180 (plus or minus 14 days) after surgery.
measure: Subjective knee evaluation form
timeFrame: On Day 360 (plus or minus 14 days) after surgery.
measure: Subjective knee evaluation form
timeFrame: On Day 720 (plus or minus 14 days) after surgery.
Other outcomes:
Locations:
city: Osnabrück
country: Germany
facility: Klinikum Osnabrück GmbH Finkenhügel, Klinik für Orthopädie, Unfall- und Handchirurgie
state: Niedersachsen
Study officials:
affiliation: Klinikum Osnabrück GmbH Finkenhügel, Klinik für Orthopädie, Unfall- und Handchirurgie, Osnabrück (Germany)
name: Martin Engelhardt, Dr.
role: PRINCIPAL_INVESTIGATOR
References: