RecruitingPhase 3NCT06499324

Surgery with Botulinum Toxin a for Incisional Hernia

Surgical Treatment of Large Incisional Hernia with Botulinum Toxin a Injection: a Double-blind Randomized Controlled Trial

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

260 participants

Start Date

Jan 17, 2025

Study Type

INTERVENTIONAL

Conditions

Incisional Hernia

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.

Eligibility

Min Age: 18 YearsMax Age: 79 Years

Inclusion Criteria7

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

Exclusion Criteria20

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);
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);
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;
Patient with severe and uncontrolled cardiovascular diseases;
Patient has received BTA within 12 weeks;
Patients with a history of seizures.

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Interventions

DRUGBTA 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.

DRUGPlacebo 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.