Surgery with Botulinum Toxin a for Incisional Hernia

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат 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® 1

Первичные конечные точки

• 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. [Срок оценки: During the 90-day postoperative period]

Вторичные конечные точки (12)

• Assessment of the impact of preoperative BTA injection on length of stay. [Срок оценки: From surgery until hospital discharge, average 5 days]
• Assessment of the impact of preoperative BTA injection on severity of surgical complications [Срок оценки: 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 [Срок оценки: During IH repair surgery]
• Assessment of the impact of preoperative BTA injection on radiological response:lateral muscles elongation [Срок оценки: 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 [Срок оценки: 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: muscular defect reduction [Срок оценки: 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: muscular defect reduction [Срок оценки: 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: hernia sac volume [Срок оценки: Between the pre-inclusion CT-scan and the CT-scan 4 weeks after BTA injection]
• Assessment of the impact of preoperative BTA injection on intra-abdominal pressure, monitored until bladder catheter removal [Срок оценки: From catheter insertion to removal]
• Assessment of the impact of preoperative BTA injection on consequences of repair on pain evolution and consumption of analgesics [Срок оценки: From 1st to 7th postoperative day and at 1, 3 , 6, and 12 months after surgery]
• Assessment of the impact of preoperative BTA injection repair results: post-operative abdominal wall disruption , clinical and radiological recurrence of the IH [Срок оценки: 90 days and 12 months after surgery]
• Assessment of the impact of preoperative BTA injection on evolution of quality of life [Срок оценки: 90 days, 6, and 12 months after surgery]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• David Moszkowicz — Colombes

Идентификаторы

NCT: NCT06499324 · APHP220805

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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