PXL01 in sodium hyaluronate for improvement of hand recovery after flexor tendon repair surgery: randomized controlled trial

Abstract

Background: Postoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery.

Methods: This prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery.

Results: The most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p = 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p = 0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p = 0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p = 0.021; PPAS: 76% vs. 35%, p = 0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p = 0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture.

Conclusions: Treatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits.

Trial registration: ClinicalTrials.gov NCT01022242; EU Clinical Trials 2009-012703-25.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and the following conflicts have been identified: Dr. M. Mahlapuu was employed by Pergamum AB, Dr. M. Wiig has received honorariums and held advisory board positions for Pergamum AB. The study was financed by Pergamum AB. Dr. K. Wiklund is employed by Pharma Consulting Group Solutions AB. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Flow of participants through trial.

Figure 2. DIPAM of the injured finger over time up to 12 months post-surgery/IMP administration in FAS (A) and PPAS (B).

Boxes show the interquartile range that contains values between the 25th and 75th percentile. Crosses (x) denote mean values, whereas lines (−) denote median values. Minimum and maximum values are indicated with bars. Circles denote outliers. At baseline, one outlier of 146 degrees in the PXL01 group is not displayed in the figure. Baseline is defined as DIPAM of the corresponding non-injured finger of the contralateral hand.

Figure 3. TAM2 absolute values of the injured finger graded according to Strickland's original classification at 12 weeks, 6 months and 12 months post-surgery/IMP administration in FAS.

Mobility of ≥150 degress is assessed as “excellent”, 125 to 149 degrees as “good”, 90 to 124 degrees as “fair” and

Figure 4. Sensory evaluation of the injured finger in patients with complete digital nerve injury at 12 weeks post-surgery/IMP administration in FAS: the first monofilament that a patient could feel.

Values are numbers (percentages) of patients in each category.