Surgery with Botulinum Toxin a for Incisional Hernia

NCT06499324 | Recruiting Phase 3

• 1 other identifier: APHP220805
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

After laparotomy, treating large incisional hernias (width \>= 10cm) proves challenging due to the progressive retraction of lateral abdominal muscles and the separation of rectus muscles. This width is a significant risk factor for repair failure and recurrence. High rates of severe postoperative morbidity, up to 50%, are reported, linked to dissection extent, increased muscular tension, and abdominal pressure. Reconstructing normal anatomy by bringing muscles together may be impossible, leading to the use of complex procedures like component separation techniques (CST), involving large aponeurotomy for muscle relaxation. Intramuscular injection of botulinum toxin A (BTA) induces reversible flaccid paralysis, with potential benefits in hernia closure, known as "chemical CST." Retrospective studies suggest reduced muscle retraction and facilitated closure without specific morbidity. Prehabilitation with BTA aims to reduce surgical morbidity compared to repair and CST. The prospective evaluation of BTA's clinical benefits, including reduced postoperative morbidity, pain, successful abdominal closure, and decreased IH recurrence risk, is lacking. A prospective randomized double-blind placebo-controlled trial is proposed to demonstrate BTA's efficacy. The hypothesis is that BTA injection before IH repair is more effective than a placebo in reducing postoperative morbimortality. Secondary expectations include a significant reduction in complete closure of the abdominal wall without CST.

Conditions

Incisional Hernia

Keywords

Incisional Hernia; Botulinum toxin A; Incisional Hernia repair; Laparatomy

Outcome Measures

Primary Outcomes (1)

• Demonstrate the efficacy of preoperative BTA injection in the lateral abdominal wall muscles reduces the rate of postoperative morbimortality after large IH (width >= 10cm) repair with mesh, compared with placebo injection.

  Occurrence of Clavien-Dindo classification grade II or higher post-operative complication

  During the 90-day postoperative period

Secondary Outcomes (12)

• Assessment of the impact of preoperative BTA injection on length of stay.

  From surgery until hospital discharge, average 5 days

• Assessment of the impact of preoperative BTA injection on severity of surgical complications

  During the 90-day postoperative period

• Assessment of the impact of preoperative BTA injection on surgical difficulty: abdominal wall closure with CST; incomplete closure of the wall with need of bridge prosthetic repair

  During IH repair surgery

• Assessment of the impact of preoperative BTA injection on radiological response:lateral muscles elongation

  Between the pre-inclusion CT-scan and the CT-scan 4 weeks after BTA injection

• Assessment of the impact of preoperative BTA injection on radiological response:lateral muscles elongation

  Between the pre-inclusion CT-scan and the CT-scan 4 weeks after BTA injection

Study Arms (2)

BTA group

EXPERIMENTAL

This arm corresponds to patients presenting with midline anterior primary or recurrent IH (subxiphoidal to suprapubic) of width \>= 10 cm, without loss of domain, scheduled for IH repair with mesh. Patients will be injected with 288 IU of BTA (XEOMIN® 100U) into the lateral muscles (18 injection sites, 16UI/8mL/injection site), 4 to 6 weeks before the treatment of the IH.

Drug: BTA group

Placebo group

PLACEBO COMPARATOR

This arm corresponds to patients presenting with midline anterior primary or recurrent IH (subxiphoidal to suprapubic) of width \>= 10 cm, without loss of domain, scheduled for IH repair with mesh. Patients will be injected with placebo of BTA (XEOMIN® 100U matching placebo) into the lateral muscles (18 injection sites, 8mL/injection site), 4 to 6 weeks before the treatment of the IH.

Drug: Placebo group

Interventions

BTA group DRUG

It consists of a blind injection of 288 IU (/144mL) of BTA (XEOMIN®) into the lateral muscles (18 injection sites, 16UI/8mL/injection site), 4 to 6 weeks before the treatment of a large anterior IH (width ≥ 10 cm) with open non absorbable mesh repair. The injection of BTA (XEOMIN®) will be done during an outpatient hospitalization, in each of the 3 lateral muscles of the abdomen on each side. To do this in the BTA group, 3 vials of 100 equivalent IU of BTA (XEOMIN® 100U), diluted to 2 IU/mL with 0.9% saline will be distributed in 3 syringes of 50 mL equipped with a 21G needle. A total of 72 mL of BTA solution (144 IU) will be injected on each side, at 3 injection points between the costal rim and iliac crest, under ultrasound control.

BTA group

Placebo group DRUG

It consists of a blind injection of placebo of BTA (XEOMIN® 100U matching placebo) into the lateral muscles (18 injection sites, 8mL/injection site), 4 to 6 weeks before the treatment of a large IH (width \>= 10 cm) with open non absorbable mesh repair. The injection of placebo of BTA (XEOMIN® 100U matching placebo) will be done during an outpatient hospitalization, in each of the 3 lateral muscles of the abdomen on each side. To do this in the control group, 3 vials of placebo of BTA (XEOMIN® 100U matching placebo), diluted with 0.9% saline will be distributed in 3 syringes of 50 mL equipped with a 21G needle. A total of 72 mL of placebo of BTA solution will be injected on each side, at 3 injection points between the costal rim and iliac crest, under ultrasound control.

Placebo group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients between 18 and 79 years;
• BMI \< 35 kg/m²;
• Written informed consent;
• Scheduled surgery for an open IH repair;
• For female of childbearing potential: using highly effective contraception.

You may not qualify if:

• Other types of IH (lateral, groin, para-stomal, portsite);
• VHWG grades 3 or 4 for the risk of surgical site infection;
• Ongoing skin infection or inflammation at the IH site or at the BTA injection site;
• Planned IH repair with slowly absorbable mesh;
• IH with loss of domain (volumetric ratio \> 25%);
• Emergency IH surgery;
• ASA score \> 3;
• Pregnancy or breastfeeding;
• Ongoing treatment with aminoglycosides;
• Severe hemostasis disorder or non-weaning treatment with curative dose anticoagulant;
• Active tobacco use (or cessation inferior to 3 months);
• Use of another investigational product within 6 months or 5 half-lives (whichever is longer), or currently participating in a prospective study with an investigational product, whether it concerns an experimental drug or a medical device;
• Patient not covered by social insurance;
• Patient under legal guardianship;
• Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose);

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

David Moszkowicz

Colombes, France, France

RECRUITING

MeSH Terms

Conditions

Incisional Hernia

Condition Hierarchy (Ancestors)

Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes

Study Officials

• David MOSZKOWICZ

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David MOSZKOWICZ, MD-PhD

CONTACT

+33 (0)1 47 60 66 02; david.moszkowicz@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The injection physician and surgeon will be blinded to the randomization group due to the transparency of BTA and the placebo. The surgeon will not know the patient's treatment during surgery as BTA does not affect muscle appearance. A blinded CT-scan, four to six weeks post-injection, will be performed; results will be kept from the surgeon to avoid unblinding, and patients will remain blinded to their randomization group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: July 12, 2024
• Study Start: January 17, 2025
• Primary Completion (Estimated): August 4, 2028
• Study Completion (Estimated): March 4, 2029
• Last Updated: January 22, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)