Clinical trial NCT01634711: Clinical Evaluation of a Resorbable PLLA Implant for Regeneration of the Anterior Cruciate Ligament (ACL)
Official title: A Prospective and Consecutive Clinical Evaluation of Soft Tissue Regeneration's L-C Ligament® in Primary ACL Reconstruction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Complete Tear, Knee, Anterior Cruciate Ligament
Keywords: ACL
Anterior Cruciate Ligament
Ligament
Resorbable polymer
Knee ligament
Lead sponsor: Soft Tissue Regeneration, Inc.
Sponsor class: INDUSTRY
First posted: 2012-07-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety of a resorbable polymer implant (Soft Tissue Regeneration's L-C Ligament) for replacement and regeneration of the anterior cruciate ligament (ACL). Approximately 15 patients at 2-3 different hospitals in Europe will participate in this study. The hypothesis of this study is that the L-C Ligament will successfully regenerate the ACL with clinical outcomes similar to or better than surgical intervention with auto graft tissue.

Detailed description: Reconstruction of the ACL is currently recommended as the standard of care following an ACL tear or rupture. The ACL has poor healing potential and repair of the damaged tissue is rarely successful. The gold standard for reconstruction of the ACL is autograft tissue, with the patellar and hamstring tendons the most common. The limitations of autograft are donor site morbidity and pain, and potential damage of the remaining tissue at the harvest site. Other problems include a limited amount of tendon available for harvesting, unpredictable resorption characteristics, and increased recovery time. Allografts are tissues such as patellar, hamstring, and Achilles tendons obtained from cadavers. The advantages of surgery with allograft are less pain and scarring, decreased surgical time, and faster rehabilitation. However, allografts can transmit disease, may elicit an unfavorable immunogenic response, and incorporate slower than autograft. Also, allografts cannot be sterilized without damaging the tissue, leading to a choice between a risk of bacterial infection and decreased tensile strength and healing potential.

The proposed study is a prospective, consecutive, non-randomized, multicentre clinical trial conducted at up to five European sites, wherein 15 study subjects will undergo primary ACL reconstruction with the L-C Ligament. After screening procedures are completed, eligible study subjects who provide written informed consent will be enrolled in the study. Subjects will undergo preoperative clinical, MRI, and radiographic evaluations and undergo primary ACL reconstruction. Follow-up clinical evaluations will be performed post-op (range 1-8 weeks), 3 months (± 3 weeks), 6 months (± 3 weeks), 12 months (± 1 month), and 24 months (± 2 months) after surgery. Assessment of safety (i.e., assessment of adverse events and complications), pain, and clinical function as well as imaging will occur.

In accordance with a separate radiographic protocol, analysis and scoring of MRI images (pre-op, 1 and 2 years), radiographs (pre- and post- op), and a CT scan post-op and at 1-year will be undertaken by an independent radiologist who will be masked to the identities of the subjects and clinical investigators. Outcome measures for imaging include position of the bone tunnels and interference screws, indirect evidence of ligament tissue remodeling, and evidence of tunnel-widening. Evidence of OA will also be monitored. The Principal Investigator and Co-Investigators will ensure that complications observed on radiographs, MRI, and CT images are reported to their ethics committee and the sponsor.

The primary objective of this study is to evaluate the safety of the L-C Ligament in primary ACL reconstruction. Safety will be evaluated by the occurrence, frequency, and severity of intra- and post- operative complications; the primary end point is one year and follow-up wil be performed for a minimum of two years. Clinical function will be assessed with the IKDC-2000 Scale and functionality of the device at two years follow-up.

The secondary objectives of this study are to determine efficacy by objectively and subjectively measuring pain, function, and the results of image analyses of the L-C Ligament in primary ACL reconstruction. Objective measures include the Lachman test, the anterior drawer test, the KT-1000 Arthrometer, the pivot-shift test, and the single-leg hop test. Pre- and post- operative objective and subjective measures include the Tegner and Lysholm scales. Pre- and post- op radiographs, MRI images pre-op, and at 1 and 2 years, and post-op and 1-year CT scans will be analyzed for position of the bone tunnels and screws, indirect evidence of ligament tissue remodeling, and evidence of widening of the bone tunnels.

Eligibility criteria: Inclusion Criteria:

1. 18 to 45 years of age.
2. Males and females.
3. If female, for the 24 months post-operative, actively practicing a contraception method, or surgically sterilised or postmenopausal.
4. Acute unilateral ACL tear, or partial or complete tear of the ACL that occurred within 18 weeks of injury, and requires reconstruction of the ACL.
5. Passive flexion ≥ 120° and passive extension on the target knee is the same as the contralateral knee.
6. Patients with all types of lateral and/or medial meniscal tears which are repairable.
7. Medial Collateral Ligament (MCL) grade 2 or less. Potential Subject is able to provide informed consent and must sign the EC-approved Informed Consent Form.
8. Must be physically and mentally willing and able to comply with post-operative rehabilitation and routinely scheduled clinical, radiographic and rehabilitation follow up visits through 24 months.

Exclusion Criteria:

1. Prior ACL reconstruction or other surgical procedure on the affected (target) knee.
2. Chronic ACL injury; interventional surgery scheduled 18 weeks or more after ACL injury.
3. Professional athletes currently engaged in active sport
4. Prior fracture of the affected (target) leg
5. Previous or current ACL injury on contra-lateral leg.
6. Multi-ligament reconstruction.
7. Malalignment with varus thrust
8. Patient greater than 193 cm tall (6' 4").
9. The patient does not follow pre-operative rehabilitation.
10. Confirmed connective tissue disorder.
11. Signs of moderate to severe degenerative joint disease (Osteoarthritis)
12. Concomitant injuries to the knee or lower extremities requiring treatment, per surgeon's discretion.
13. Severe pain, swelling, or redness within 24 hours prior to surgery.
14. Complete or partial Post Cruciate Ligament (PCL) tear.
15. Any of the following: 1/3rd meniscal resection; complex double-bucket tear; partially repaired meniscal tears.
16. Patient requires treatment of articular cartilage on target leg
17. The patient is mentally compromised.
18. The patient has a neuromuscular disorder that would engender unacceptable risk of knee instability, prosthesis fixation failure, or complications in postoperative care.
19. The patient has a diagnosed systemic disease that would affect his/her safety or the study outcome.
20. The patient has an active or latent infection in or about the affected knee joint or an infection site distant from the knee that may spread to the knee hematogenously.
21. Pregnant based on a positive beta hCG serum or an in vitro diagnostic test result or breast-feeding.
22. The patient is obese with a BMI greater than or equal to 35.
23. The patient has a known allergy to PLLA.
24. The patient has a medical condition or comorbidity that would interfere with study participation.

Primary outcomes:
measure: The anterior cruciate ligament (ACL) is clinically functional at one year follow-up
timeFrame: One year
Secondary outcomes:
measure: International Knee Documentation Committee (IKDC) score
timeFrame: Pre-op, 6, 12, and 24 months
measure: Tegner Activity score
timeFrame: Pre-op, 6, 12, & 24 months
measure: Lachman test
timeFrame: Pre-op, 6, 12, and 24 months
measure: KT-1000 Arthrometer score
timeFrame: Pre-op, 6, 12, 24 months
measure: Lysholm Knee Score
timeFrame: pre-op, 6, 12, 24 months
measure: Lachman Test score
timeFrame: pre-op, 6, 12, 24 months
measure: Pivot Shift
timeFrame: pre-op, 6, 12, 24 months
measure: Single-Leg Hop test
timeFrame: pre-op, 6, 12, 24 months
measure: Anterior Drawer Test
timeFrame: pre-op, 6, 12, 24 months
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Martini ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken - locatie Weezenlanden
Study officials:
References: