Surgical treatment of large incisional hernia with botulinum toxin A injection: a double-blind randomized controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Jan 2025 → ongoing

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Programme Hospitalier de Recherche Clinique - PHRC 2021 (French Ministry of Health)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To demonstrate that preoperative BTA injection in the lateral abdominal wall muscles reduces the rate of postoperative morbi-mortality after large IH (width ≥ 10cm) repair with mesh, compared with placebo injection.

Secondary objectives 8

1. To assess the impact of preoperative BTA injection on length of hospital stay
2. To assess the impact of preoperative BTA injection on severity of surgical complications
3. To assess 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
4. To assess the impact of preoperative BTA injection on radiological response: lateral muscles elongation, muscular defect reduction, and hernia sac volume on CT-scan without contrast injection 4 weeks after BTA injection
5. To assess the impact of preoperative BTA injection on intra-abdominal pressure, monitored until bladder catheter removal
6. To assess the impact of preoperative BTA injection on consequences of repair on pain evolution and consumption of analgesics until 12 months after surgery
7. To assess the impact of preoperative BTA injection repair results: post-operative abdominal wall disruption on day 90, clinical and radiological recurrence of the IH at 1-year; reoperation for recurrence of the IH at 1 year postoperative
8. To assess the impact of preoperative BTA injection on evolution of quality of life between inclusion and 90 day, 6 months, and 1-year postoperative

Conditions and MedDRA coding

incisional hernia

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

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 20

1. Other types of IH (lateral, groin, para-stomal, port-site) are allowed, provided they are not the target of surgical treatment (i.e., not intended to be repaired as part of the current intervention)
2. Severe hemostasis disorder or non-weaning treatment with curative dose anticoagulant
3. Active tobacco use (or cessation inferior to 3 months)
4. 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
5. Patient not covered by social insurance
6. Patient under legal guardianship
7. Hypersensitivity to the active substance (Clostridium Botulinum neurotoxin type A) or to any of the excipients (Human albumin, sucrose)
8. 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)
9. VHWG grades 3 or 4 for the risk of surgical site infection
10. Ongoing skin infection or inflammation at the IH site or at the BTA injection site
11. Planned IH repair with slowly absorbable mesh
12. IH with loss of domain (volumetric ratio > 25%)
13. Emergency IH surgery
14. ASA score > 3
15. Pregnancy or breastfeeding
16. Ongoing treatment with aminoglycosides
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of Clavien-Dindo classification grade II or higher post-operative complication during the 90-day postoperative period.

Secondary endpoints 8

1. Length of hospital stay in days
2. Severity of complication according to the Clavien-Dindo classification during the 90-day postoperative period
3. Occurrence of CST during IH repair, Occurrence of incomplete wall closure (bridge closure) during IH repair
4. Sum of the length variation of the left and right lateral muscles (cm), sum of the width variation of the left and right lateral muscles (cm), sum of the width (cm) and surface (cm²) variation of the muscular defect; peritoneal sac volume (cm3) variation, between the pre-inclusion CT and the CT 4 weeks after BTA injection
5. Intravesical pressure, measured daily until bladder catheter removal
6. Pain on Analogical Visual Scale at inclusion, from 1st to 7th postoperative day and at 1, 3 (90 days), 6, and 12 months after surgery ; 90-day postoperative prescription of type 3 analgesics
7. Occurrence of post-operative abdominal wall disruption during a 90 days period after surgery; occurrence of clinical recurrence of the IH during the first year after surgery; occurrence of radiological recurrence of the IH at 12 months post-surgery; 1-year postoperative occurrence of clinical and radiological recurrence of the IH, or reoperation for recurrence;
8. EQ-5D-5L at inclusion, 90 days, 6, and 12 months after surgery

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David MOSZKOWICZ

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr David MOSZKOWICZ

Locations

1 EU/EEA country · 18 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications