Clinical trial NCT03441295: LIBRE (Ligamys, Internal Bracing, REconstruction) Study: Comparing Three Surgery Techniques After an Acute ACL Rupture.
Official title: Single-blind, Multi-centre, Randomized Controlled Trial Comparing Ligamys Anterior Cruciate Ligament (ACL) Repair, Internal Bracing ACL Repair and Conventional ACL Reconstruction for Relative Clinical Efficacy and Economic Benefit.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Anterior Cruciate Ligament Rupture
Keywords: ACL
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: Universitair Ziekenhuis Brussel
name: Onze Lieve Vrouw Hospital
First posted: 2018-02-22
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study 1 comparing Ligamys (DIS) and Internal Bracing (N=48). Study 2 comparing Internal Bracing and ACL Reconstruction (N=48).
Primary purpose: TREATMENT

Brief summary: Single-blind, multi-centre, prospective, randomized controlled trial comparing Ligamys Anterior Cruciate Ligament (ACL) repair, Internal Bracing ACL repair and conventional ACL reconstruction for relative clinical efficacy and economic benefit.

Patients with a primary proximal acute ACL rupture will be included in either study 1 (0-4 weeks post rupture) or study 2 (5-12 weeks post rupture) of the LIBRE study.

Detailed description: Rationale The conventional operative treatment of an anterior cruciate ligament (ACL) rupture is an ACL reconstruction, whereby the residual ruptured ACL is removed and replaced by an autograft hamstring tendon.

Recently, two alternative natural healing techniques have been developed and proof of concept have been established. The two repair techniques are: Dynamic Intraligamentary Stabilization (DIS) and Internal Brace Ligament Augmentation (IBLA). Both DIS and IBLA allow the rupture to heal by itself. The biggest difference between the two techniques is that the DIS system consists of a polyethylene suture and a spring screw system, which stabilizes the knee joint with the same force during flexion and extension of the knee, and the IBLA system consists of a 2mm high molecular weight polyethylene FiberTape®.

Objective The aim is to identify the optimal ACL technique for treating an acute ACL injury that can deliver an enhanced clinical efficacy and economic benefit for two time frames (0-4 weeks and 5-12 weeks) following ACL rupture.

Study design Two separate, interventional, single-blind, comparative, multi-centre, randomized controlled trials (RCTs) will be conducted. The University Hospital of Antwerp (UHA), University Hospital of Brussels (UHB) and OLV Hospital (OLVH) are the three participating sites. A total of 96 patients will be included in the study, 48 for study 1 and 48 for study 2.

The anticipated study duration is 72 months which will include a five month starting-up phase, 40 month recruitment period, a 24 month follow-up period and three months for final analysis. The study data will be collected over three periods: pre-operative, per-operative and post-operative.

To meet the aim the time-dependent nature of ACL repair surgery has to be taken into account. As the DIS should be performed within a short period after the ACL rupture, study 1 is limited to 4 weeks after ACL rupture. IBLA can be performed up to 12 weeks after ACL rupture, therefore the time limit for study 2 is 12 weeks after ACL rupture. ACL reconstruction is preferably performed when the knee has 'cooled down', and this is from 5 weeks post-rupture. There is no time limit for the ACL reconstruction, since this can be performed up to several years post-rupture.

• Study 1: RCT 1 DIS versus IBLA within 4 weeks after the ACL rupture.

• Study 2: RCT 2 IBLA versus the conventional ACL reconstruction between 5-12 weeks after the ACL rupture.

Study population Patients with a primary acute proximal ACL rupture, below the age of 50 years. The ACL remnant must be suitable for repair.

Intervention The conventional ACL reconstruction, DIS or IBLA surgery.

Main study objectives Primary outcome: Difference of 13 points in IKDC score between the reconstruction technique and the repair techniques (DIS/IBLA) 6 months postoperatively.

Main secondary outcomes: Failure/re-rupture, Tegner score, Lysholm score, EQ-5D-5L, return to work/sport, Lachman test, Pivot Shift test and complications.

Nature and extent of the burden and risks associated with participation, and benefit Proof of concept have been established and the expected complications are similar in the three treatment arms. The major benefit of the alternative repair techniques is the preservation of the native ACL and its own proprioceptors possibly leading to a faster recovery time.

Eligibility criteria: Inclusion Criteria:

* • Primary acute proximal ACL rupture (MRI and per-operative confirmation): 3-digit ACL rupture classification, type A (supplement 1)

  * Between 18-50 years, male or female
  * Randomization and surgery within 4 weeks after the ACL rupture (Study 1)
  * Randomization and surgery between 5-12 weeks after the ACL rupture (Study 2)
  * The ACL remnant is suitable for repair in the three treatment groups: the distal ACL remnant must be in contact with the proximal remnant/femoral condyle for at least 75% (per-operative confirmation)
  * The patient is mentally and verbally capable of participating in the study.
  * Written informed consent (according to the International Conference on Harmonisation (ICH)-GCP Guidelines).

Exclusion Criteria:

* • Known posterior cruciate ligament (PCL) and/or posterolateral ligamentous complex (PLC), lateral collateral ligament (LCL) or medial collateral ligament (MCL) grade 3 injury.

  * Known osseous fractures that could impair revalidation and/or ACL repair
  * Patients with neurological disorders or systemic diseases
  * Patients with trauma/fractures in the lower limb in the past 6 months that could influence rehabilitation
  * Non-sportive patients with a Tegner score of \<3: these patients could probably counteract instability complaints with intensive physiotherapy.
  * Any inflammatory disease, Rheumatoid Arthritis (RA), Spondyloarthropathy (SpA), active malignancy
  * Patient not suited for intervention due to lack of mobility, meaning not achieving 90° of flexion before surgery.

Primary outcomes:
measure: International Knee Documentation Committee (IKDC) Score
timeFrame: Baseline (pre-rupture), week 13, week 26, week 52, week 104. At 6 months follow-up the primary outcome will be measured, a change of 13 IKDC points between the treatments is considered clinically meaningful.
Secondary outcomes:
measure: Failure (re-rupture/instability complaints)
timeFrame: Day 1, week 2, week 6, week 13, week 26, week 52, week 104.
measure: Tegner score
timeFrame: Baseline (pre-rupture), week 13, week 26, week 52, week 104.
measure: Lysholm score
timeFrame: Baseline (pre-rupture), week 13 post-operative, week 26 post-operative, week 52 post-operative, week 104 post-operative
measure: EQ-5D-5L
timeFrame: Baseline (pre-operative), day 1, week 2, week 6, week 13, week 26, week 52, week 104.
measure: Return to work/sport
timeFrame: Day 1, week 2, week 6, week 13, week 26, week 52, week 104.
measure: Isokinetic measurement (Biodex/CSMI)
timeFrame: Pre-operative, week 13, week 26, week 52.
measure: MRI
timeFrame: Pre-operative, week 26, week 52, week 104.
measure: Visual Analogue Scale (VAS) Pain
timeFrame: Baseline (pre-operative), day 1, week 2, week 6, week 13, week 26, week 52, week 104.
measure: Visual Analogue Scale (VAS) Satisfaction
timeFrame: Week 6, week 13, week 26, week 52, week 104.
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: University Hospital, Antwerp
state: Antwerp
city: Jette
country: Belgium
facility: University Hospital, Brussels
state: Brussels
city: Aalst
country: Belgium
facility: OLV Hospital
state: Oost-Vlaanderen
Study officials:
affiliation: UH, Antwerp
name: Christiaan Heusdens
role: PRINCIPAL_INVESTIGATOR
References:
citation: Heusdens CHW, Zazulia K, Roelant E, Dossche L, van Tiggelen D, Roeykens J, Smits E, Vanlauwe J, Van Dyck P. Study protocol: a single-blind, multi-center, randomized controlled trial comparing dynamic intraligamentary stabilization, internal brace ligament augmentation and reconstruction in individuals with an acute anterior cruciate ligament rupture: LIBRƎ study. BMC Musculoskelet Disord. 2019 Nov 18;20(1):547. doi: 10.1186/s12891-019-2926-0.