Sensory Recovery of Digital Nerves After Microsurgical Epineural Neurorrhaphy Alone or in Combination With Tisseel - RET (RET)

A Prospective Randomized Study to Evaluate Sensory Recovery of Digital Nerves After Primary Repair Performed by Microsurgical Epineural End-to-end Neurorrhaphy Alone, or in Combination With an Enwrapping With Fibrin Sealant Tisseel®

Evaluation of sensitivity after primary surgical treatment of digital nerve injuries with microsurgical epineural end-to-end neurorrhaphy alone or in combination with the fibrin glue Tisseel®

Study Overview

• Status: Not yet recruiting
• Conditions: Digital Nerve Injuries
• Intervention / Treatment: Drug: Tisseel®

Detailed Description

Lacerations of the fingers with nerve injuries are a common reason for a presentation at the surgical emergency ward of the Inselspital Bern. The patient complains of either reduced sensitivity or even complete numbness in the affected finger. This leads to a clear functional loss in daily activities and should be reliably tested during the clinical examination. If a nerve lesion is suspected, the wound and the affected nerve should be explored in the operating room. If the suspicion is confirmed, the sheath of the two nerve endings can be sewn under the microscope or with surgical loupes.

Tension free microsurgical epineural end-to-end neurorrhaphy of digital nerves after sharp or blunt lesions is a simple and effective procedure in order to regain sensory recovery and prevent neuroma formation.

Industry is promoting different aids in order to achieve better outcomes after repair - such as tissue glue, grafts and conduits. These products are more or less expensive, which becomes more and more important as the general cost in the Swiss health system are progressively increasing.

The aim of this randomized, prospective controlled study is thus to compare the clinical benefit of a primary epineural end-to-end neurorrhaphy combined with fibrin glue (Tisseel®) versus a simple epineural end-to-end neurorrhaphy alone.

• Study Type: Interventional
• Enrollment (Anticipated): 74
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Esther Voegelin, Prof. Dr.; Phone Number: +41794401987 +41316328014; Email: esther.voegelin@insel.ch
• Study Contact Backup: Name: Léna Dietrich, Dr. med.; Phone Number: +41799463620 +41316326440; Email: lena.dietrich@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Insel Gruppe AG
    • Contact: Esther Voegelin, Prof.; Phone Number: +41 31 6323534; Email: esther.voegelin@insel.ch
    • Contact: Léna Dietrich, Dr.; Phone Number: +41 31 632 6440; Email: lena.dietrich@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written consent to participate in the study
• Acute digital nerve lesion(s) distal to the superficial arterial arch on one or more fingers that qualify for primary direct end-to-end microsurgical epineural neurorrhaphy
• Age ≥18 years

Exclusion Criteria:

• Lesions that do not allow a tension-free direct suture, partial transections, amputation, re-vascularisation
• Age < 18 years
• Pre-operation on the injured finger
• Clinical comparison with contralateral finger not possible (e.g. due to amputation).
• Treatment that is known to inhibit the growth/regeneration of nerves impaired or can cause neuropathy - such as chemo- or radiotherapy before or during the whole study
• Systemic and local neurological impairments (polyneuropathy, diabetes mellitus, carpal tunnel syndrome, etc.)
• History of vascular diseases like Raynaud's disease syndrome that affects blood flow or sensation in the upper can affect the extremities
• Known or suspected non-compliance
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, or dementia
• Women who are pregnant (urin pregnancy test) or breast feeding. Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
• Previous enrolment into the current study
• Enrolment of the investigator, his/her family members, employees and other dependent persons
• Contraindications to the investigational product, e.g. known allergy to components of the Tisseel® fibrin glue
• Participation in another interventional study within the 30 days preceding and during the present study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Microsurgical end-to-end neurorrhaphy alone; This group of patients receives a simple, tension-free, end-to-end microsurgical neurorrhaphy alone (without fibrin glue)
Experimental: Microsurgical end-to-end neurorrhaphy in combination with an enwrapping with fibrin sealant Tisseel®; This group of patients receives a simple, tension-free, end-to-end microsurgical neurorrhaphy in combination with an enwrapping with fibrin sealant Tisseel®.	Drug: Tisseel®; The investigational medical product (IMP) in this study is Tisseel®, which is a tissue sealer consisting of two components: Sealer protein: Human fibrinogen as "glue" component and synthetic Aprotinin, which delays fibrinolysis.; Human thrombin: Thrombin is an unique molecule that functions both as a procoagulant and anticoagulant. It activates platelets through its receptor on the platelets and regulates its own. generation by activating coagulation factors V, VIII and even XI resulting in a burst of thrombin formation. Its indications are a better hemostasis, enforcement of vessel/gastrointestinal sutures and tissue sutures (mesh grafts, flaps etc).; Other Names: Neurorraphy alone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
two point discrimination	For this purpose a standardized two-point-discriminator (PADGETT DeMayo Two-Point Discrimination Device, Used for Post hand surgery diagnostic. MFID: PM-855) is used	preoperative
two point discrimination	For this purpose a standardized two-point-discriminator (PADGETT DeMayo Two-Point Discrimination Device, Used for Post hand surgery diagnostic. MFID: PM-855) is used	6 weeks postoperative
two point discrimination	For this purpose a standardized two-point-discriminator (PADGETT DeMayo Two-Point Discrimination Device, Used for Post hand surgery diagnostic. MFID: PM-855) is used	12 weeks postoperative
two point discrimination	For this purpose a standardized two-point-discriminator (PADGETT DeMayo Two-Point Discrimination Device, Used for Post hand surgery diagnostic. MFID: PM-855) is used	24 weeks postoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuroma formation	presence of Hofmann-Tinel sign; Allodynographia/Mapping (Semmes-Weinstein Monofilament (SWMF) assessment as described by Spicher et al. (17); Sammons Preston Rolyan) performed by a trained hand therapist; detection of a neuroma in ultrasound examination (measurement of three cross-section areas: proximal, distal and at the level of the neurorrhaphy) performed by a therefore certified hand surgeon (Philips iU22 Medical system or Philips 70 affiniti)	6 weeks postoperative
Grip strength	using a JAMAR dynamometer	12 weeks postoperative
Active range of motion	using a goniometer	6 weeks postoperative
Pain with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	6 weeks postoperative
quickDASH score (Disabilities of the Shoulder, Arm and Hand)	a 11 item questionnaire: filled out by the patient	preoperative
STI-Test: (Shape-Texture Identification test)	This test is a standardized outcome measure of sensory function of the median and ulnar nerves of the hand: max. score for completed test = 6 points, min. score = 0	12 weeks postoperative
Neuroma formation	presence of Hofmann-Tinel sign; Allodynographia/Mapping (Semmes-Weinstein Monofilament (SWMF) assessment as described by Spicher et al. (17); Sammons Preston Rolyan) performed by a trained hand therapist; detection of a neuroma in ultrasound examination (measurement of three cross-section areas: proximal, distal and at the level of the neurorrhaphy) performed by a therefore certified hand surgeon (Philips iU22 Medical system or Philips 70 affiniti)	12 weeks postoperative
Neuroma formation	presence of Hofmann-Tinel sign; Allodynographia/Mapping (Semmes-Weinstein Monofilament (SWMF) assessment as described by Spicher et al. (17); Sammons Preston Rolyan) performed by a trained hand therapist; detection of a neuroma in ultrasound examination (measurement of three cross-section areas: proximal, distal and at the level of the neurorrhaphy) performed by a therefore certified hand surgeon (Philips iU22 Medical system or Philips 70 affiniti)	24 weeks postoperative
Neuroma formation	presence of Hofmann-Tinel sign; Allodynographia/Mapping (Semmes-Weinstein Monofilament (SWMF) assessment as described by Spicher et al. (17); Sammons Preston Rolyan) performed by a trained hand therapist; detection of a neuroma in ultrasound examination (measurement of three cross-section areas: proximal, distal and at the level of the neurorrhaphy) performed by a therefore certified hand surgeon (Philips iU22 Medical system or Philips 70 affiniti)	48 weeks postoperative
Grip strength	using a JAMAR dynamometer	24 weeks postoperative
Grip strength	using a JAMAR dynamometer	48 weeks postoperative
Active range of motion	using a goniometer	12 weeks postoperative
Active range of motion	using a goniometer	24 weeks postoperative
Active range of motion	using a goniometer	48 weeks postoperative
Pain with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	12 weeks postoperative
Pain with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	24 weeks postoperative
Pain with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	with the Numeric Rating Scale (NRS): 0 indicating no and 10 indicating maximum pain	48 weeks postoperative
quickDASH score (Disabilities of the Shoulder, Arm and Hand)	a 11 item questionnaire: filled out by the patient	6 weeks postoperative
quickDASH score (Disabilities of the Shoulder, Arm and Hand)	a 11 item questionnaire: filled out by the patient	12 weeks postoperative
quickDASH score (Disabilities of the Shoulder, Arm and Hand)	a 11 item questionnaire: filled out by the patient	24 weeks postoperative
quickDASH score (Disabilities of the Shoulder, Arm and Hand)	a 11 item questionnaire: filled out by the patient	48 weeks postoperative
STI-Test: (Shape-Texture Identification test)	This test is a standardized outcome measure of sensory function of the median and ulnar nerves of the hand: max. score for completed test = 6 points, min. score = 0	24 weeks postoperative
STI-Test: (Shape-Texture Identification test)	This test is a standardized outcome measure of sensory function of the median and ulnar nerves of the hand: max. score for completed test = 6 points, min. score = 0	48 weeks postoperative

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: Baxter Healthcare Corporation
• Investigators: Study Chair: Esther Vögelin, Prof. Dr., Insel Gruppe AG, University of Bern

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2023
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: July 6, 2022
• First Submitted That Met QC Criteria: August 4, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: 2021-02050

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No