Surgery with Botulinum Toxin a for Incisional Hernia

NCT ID: NCT06499324

Last Updated: 2025-01-22

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-17
• Study Completion Date: 2029-03-04

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.

Detailed Description

Almost 20% of patients will develop an incisional hernia (IH) after laparotomy. Each year in France, around 30,000 patients undergo IH repair with mesh [PMSI, 2017]. The treatment of large IH (width>=10cm) is difficult due to the progressive retraction of the lateral abdominal muscles associated with the separation of the rectus muscles. The IH width is a major risk factor of failure of the repair and recurrence. Furthermore, high rates of severe postoperative morbidity, up to 50%, have been reported and related to the extent of dissection and increase of muscular tension and abdominal pressure. Thus, bringing the muscles together to reconstruct the normal anatomy may be impossible and lead the surgeon to use complex and morbid technical procedures, such as component separation techniques (CST), consisting in large aponeurotomy for relaxation of the lateral muscles. The intramuscular injection of botulinum toxin A (BTA) makes it possible to obtain a reversible flaccid paralysis of the striated muscle fibers and its advantage has been demonstrated for the treatment of neurological spasticity. Its use to obtain a relaxation of the lateral muscles of the abdomen, so-called "chemical CST", reduce their retraction and facilitate hernia closure, as studied in retrospective studies, without specific morbidity. In particular, prehabilitation with BTA injection, is supposed to reduce surgical morbidity in comparison with surgical repair and CST. The expected clinical benefit, in terms of reduction of postoperative morbidity and pain, successful closure of the abdomen, and reduction of the risk of recurrence of the IH, has never been evaluated prospectively. Thus, a prospective randomized double-blind placebo-controlled trial would be the best method to demonstrate the benefit of BTA injection. The investigators hypothesize that BTA injection in the lateral muscles before IH repair is more effective than placebo injection in reducing postoperative morbimortality. Secondarily, the investigators expect that BTA injection is associated with a significant reduction of complete closure of the abdominal wall without CST.

Conditions

Incisional Hernia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

BTA group

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.

Group Type: EXPERIMENTAL

BTA group

Intervention Type: 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.

Placebo group

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.

Group Type: PLACEBO_COMPARATOR

Placebo group

Intervention Type: 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.

Interventions

BTA group

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.

Intervention Type: DRUG

Placebo group

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients between 18 and 79 years;

2. BMI < 35 kg/m²;

3. Midline anterior primary or recurrent IH (subxiphoidal to suprapubic), of width >= 10 cm, on the abdominopelvic CT without injection of contrast agent, performed in the 6 months before inclusion (EHS W3);

4. IH without loss of domain, defined by the ratio: (volume of the peritoneal sac) / (total peritoneal volume) < 25%, on the abdominal CT without injection of contrast agent, performed in the 6 months before inclusion;

5. Written informed consent;

6. Scheduled surgery for an open IH repair;

7. For female of childbearing potential: using highly effective contraception.

Exclusion Criteria

1. Other types of IH (lateral, groin, para-stomal, portsite);

2. VHWG grades 3 or 4 for the risk of surgical site infection;

3. Ongoing skin infection or inflammation at the IH site or at the BTA injection site;

4. Planned IH repair with slowly absorbable mesh;

5. IH with loss of domain (volumetric ratio > 25%);

6. Emergency IH surgery;

7. ASA score > 3;

8. Pregnancy or breastfeeding;

9. Ongoing treatment with aminoglycosides;

10. Severe hemostasis disorder or non-weaning treatment with curative dose anticoagulant;

11. Active tobacco use (or cessation inferior to 3 months);

12. 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;

13. Patient not covered by social insurance;

14. Patient under legal guardianship;

15. Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose);

16. Generalized disorders of muscle activity (e.g. myasthenia gravis, Lambert-Eaton syndrome, peripheral motor neuropathic diseases (e.g. amyotrophic lateral sclerosis or motor neuropathy), facial nerve disorders, underlying neurological disorders) and history of dysphagia and aspiration);

17. Patient with ongoing treatment with medicinal products that interfere with the transfer of an impulse from a nerve to a muscle, e.g. tubocurarine-type muscle relaxants that weaken the muscles;

18. Patient with severe and uncontrolled cardiovascular diseases;

19. Patient has received BTA within 12 weeks;

20. Patients with a history of seizures.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David MOSZKOWICZ

Role: PRINCIPAL_INVESTIGATOR

APHP

Locations

David Moszkowicz

Colombes, France, France

Site Status: RECRUITING

Countries

France

Central Contacts

David MOSZKOWICZ, MD-PhD

Role: CONTACT

david.moszkowicz@aphp.fr

+33 (0)1 47 60 66 02

Facility Contacts

David Moszkowicz, Pr

Role: primary

david.moszkowicz@aphp.fr

01 47 60 63 84

Other Identifiers

APHP220805

Identifier Type: -

Identifier Source: org_study_id