Preoperative BOTOX® Injection for Large Ventral Hernia Repair

Not Applicable

Recruiting

• Conditions: Hernia Abdominal Wall; Hernia Incisional; Botox Injection; Hernia Incisional Ventral; Hernia Repair With Compartment Syndrome; Hernia Surgery; Hernia
• Interventions: Procedure: OnabotulinumtoxinA Injection; Procedure: Saline (placebo) Injection; Drug: OnabotulinumtoxinA; Drug: 0.9 % Normal Saline; Procedure: Open Ventral Hernia Repair

• Registration Number: NCT07220382
• Lead Sponsor: The Cleveland Clinic

Brief Summary

This study is for adults who need open surgery to repair a very large abdominal (ventral) hernia. This study tests whether a one-time, image-guided injection of a medicine commonly known as "BOTOX®" (onabotulinumtoxinA) into the side abdominal muscles 3-7 weeks before surgery helps surgeons close the abdominal wall fully at the end of the operation. Closing the muscle and tissue layers ("primary fascial closure") is linked to fewer problems after surgery and better quality of life.

Participants will be randomly assigned (like a coin flip) to receive either the BOTOX® medicine or a saltwater (placebo) injection. Neither patients nor the care team will know which one was given. All participants will still have their planned hernia repair in the standard way that we repair patients who are not part of the study. The study will track whether the abdomen can be closed without leaving a gap, and investigators will also look at recovery, complications, time in the ICU or on a ventilator, length of stay, pain, and quality-of-life scores. Most information will be collected during participants' hospital stay, but the investigators will continue to see how participants are doing up to 2 years after surgery. Short phone check-ins will occur before surgery, and after surgery follow-up happens around 30 days, 90 days, 1 year, and 2 years.

Possible risks from the injection include temporary muscle weakness, trouble swallowing or breathing, pain or infection at the injection site, and (if CT is used for guidance) a small amount of radiation exposure. Surgery itself carries the usual risks (pain, bleeding, wound problems). Benefits are not guaranteed, but the injection may make closure easier and recovery smoother. About 188 people will take part at Cleveland Clinic.

Detailed Description

Background and Rationale:

Massive ventral hernias (pre-op axial width ≥15 cm and/or Tanaka volume ratio \>25%) seldom achieve primary fascial closure (PFC) and are associated with higher respiratory morbidity, intensive care unit (ICU) utilization, post-operative pain, hospital length of stay (LOS), cost, and recurrence. Spasticity/fibrosis of the external oblique-internal oblique-transversus abdominis (EO/IO/TA) complex likely limits lateral abdominal wall compliance and impedes midline medialization. Pre-operative, image-guided onabotulinumtoxinA (BOTOX®) has been proposed to elongate the lateral wall, enlarge the functional abdominal domain, reduce closure pressures, and thereby increase the primary fascial closure (PFC) rate. Prior institutional data show \~77% PFC in this population without pre-op toxin, whereas retrospective series suggest \~95% with toxin utilization, motivating a definitive randomized trial.

Design:

Single-center, randomized, double-blind, placebo-controlled superiority trial. Randomization uses pre-generated block allocation (statistician-generated). Analyses will be intention-to-treat (ITT), with a parallel per-protocol (PP) analyses limited to participants who receive the assigned injection and undergo AWR within 21-48 days post-injection. A single interim analysis is planned at 50% completion of primary endpoint. Intention-to-treat (ITT) is primary method of analysis; however, a per-protocol (PP) analysis will also be conducted as this supports causal inference among adherent participants. An independent DMC will review interim results and advise on continuation/early stopping.

Interventions:

Fully described in 'Arms and Interventions' section. Participants will either receive image-guided injections of BOTOX® at six sites on the lateral abdominal wall (three sites per side) with a total of 300 units give (2 u / cc concentration; 25 cc at each site); or, participants will receive the same volume of a 0.9% saline solution (25 cc at each site).

End Points and Outcomes:

Fully described in the 'Outcomes Measures' section. Primary endpoint is primary fascial closure (PFC), the successful closure of hernia defect at the conclusion of the case. Additional secondary outcomes regarding clinical course and patient-reported outcomes will be captured at 30 days, 90 days, 1 year, and 2 years.

Exploratory outcomes include cost and healthcare utilization information, as well as comparison of physiological parameters between treatment groups.

Data Stewardship:

Primary data capture occurs in the ACHQC registry, supplemented by an institutional REDCap database for variables not routinely captured (e.g., physiologic measures) in the registry.

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-17
• Study First Submitted QC: 2025-10-21
• Last Update Submitted: 2025-10-22
• Study First Posted: 2025-10-23
• Last Update Posted: 2025-10-24
• Study Start: 2025-11-03
• Primary Completion: 2027-12-15
• Study Completion: 2029-12-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

• Adult (greater than or equal to 18 years of age)
• Candidate for elective open repair of ventral hernia
• Preoperative imaging demonstrating either:
• ventral hernia defect width of at lest 15 cm; AND/OR,
• Tanaka volume ratio of at least 25%
• Planned elective hernia repair in an open fashion via a midline laparotomy with posterior component separation and transversus abdominis release

Exclusion Criteria

• Emergent cases
• Pregnancy and/or breastfeeding at time of intramuscular injection
• Inability to provide informed consent
• Inability to receive either study intervention (i.e. allergy to local anesthetics utilized for intervention administration, allergy and/or contraindication to any botulinum toxin, inability to attend outpatient administration of study intervention, inability to conform to safety check schedule)
• Known congenital or acquired neuromuscular disorder
• Presence of stoma
• Current infection at time of intramuscular injection
• Flank hernias s defined by EHS L1-L4
• BMI > 45 kg/m^2
• Diaphragmatic hemiparesis or chronic obstructive pulmonary disease (COPD) with chronic oxygen dependence

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
OnabotulinumtoxinA Group	OnabotulinumtoxinA Injection	These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
Placebo Group	Saline (placebo) Injection	These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.
OnabotulinumtoxinA Group	OnabotulinumtoxinA	These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
OnabotulinumtoxinA Group	Open Ventral Hernia Repair	These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
Placebo Group	0.9 % Normal Saline	These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.
Placebo Group	Open Ventral Hernia Repair	These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.

Primary Outcome Measures

Name	Time	Method
Primary Fascial Closure (PFC) at conclusion of Hernia Surgery (Yes / No, determined by surgeon)	This will be measured (recorded) on the day of the hernia repair surgery, which will be 21 to 48 days after receiving your BOTOX injection.	Primary fascial closure (PFC) is the successful closure of the hernia. It will be defined in a binary, categorical manner as: "Yes" (fascial closed) or "No" (fascia not closed and bridging mesh required). To be considered "Yes" for PFC, the midline anterior fascia must be completely re-approximated via absorbable running or figure-of-eight sutures. If any segment of the anterior fascia cannot be approximated and closed, the patient will require anterior bridging and this would be considered a failure of PFC.; Surgeons will decide if the fascia can be closed or if it cannot be closed by their expertise and discretion. No prespecified criteria have been established which dictate operative decision-making. The study team will record an outcome of "Yes" for PFC if the fascia is successfully closed by the surgeon via an eligible technique as previously described.

Secondary Outcome Measures

Name	Time	Method
30-Day Surgical Site Infection (SSI) - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Any incisional or organ/space infection within 30 days, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
30-Day Readmission - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Any inpatient hospital readmission within 30 days of index surgery. "How measured": EHR review/REDCap; unit = participants (%).
30-Day Hospital Length of Stay - Days	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Days from operation to hospital discharge. "How measured": EHR discharge date minus surgery date; unit = days.
30-Day ICU Admission - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Any ICU care during the index stay or within 30 days (planned or unplanned). "How measured": EHR/REDCap; unit = participants (%).
30-Day Surgical Site Occurrence (SSO) - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 30 days of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
30-Day Post-operative Ileus - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Ileus requiring clinical management within 30 days. Defined as placement of an nasogastric tube or clinical diagnosis by surgeon based on intolerance of oral intake or delayed return of bowel function. "How measured": medical record review or clinician diagnosis. Unit = participants (%).
30-Day SSOPI (Surgical Site Occurrence Requiring Procedural Intervention) - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 30 days. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).
90-Day Reoperation - Proportion of Participants (%)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Any return to the operating room related to the index surgery within 90 days. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).
30-Day Reoperation - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Any return to the operating room related to the index surgery within 30 days. "How measured": EHR/REDCap; unit = participants (%).
Duration of Mechanical Ventilation (Index Hospitalization) - Hours	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Total ventilator time during and after surgery until final extubation during the index stay. Will be sub-divided as during surgery and after surgery. "How measured": anesthesia/intensive care record; unit = hours (may also be displayed as days:hours)
30-Day Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).
30-Day Myocardial Infarction (MI) - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	MI within 30 days per treating clinician diagnosis. "How measured": medical record review, patient interview, and/or clinical diagnosis. Unit = participants (%).
30-Day Renal Failure/Acute Kidney Injury (AKI) - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Acute kidney injury/failure within 30 days. "How measured": clinician diagnosis, medical record review, and/or KDIGO Guidelines. Unit = participants (%).
30-Day Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Intensity Short Form 3a - T-Score (Raw Response score range: 0-10, Higher = Worse Pain)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.
90-Day SSO - Proportion of Participants (%)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 90 days of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
90-Day Comprehensive Complication Index (CCI) Score at 90 Days - Score	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Comprehensive Complication Index® score, which is a weighted score based on the number of complications in each Clavien-Dindo group within 90 postoperative days. "How measured": the individuals CCI score at 90-days, as calculated via https://www.cci-calculator.com/.
30-Day Pneumonia - Proportion of Participants (%)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Clinically diagnosed pneumonia within 30 days. "How measured": patient interview, medical record review, or clinical diagnosis. Unit = participants (%).
30-Day Complication Severity (Clavien-Dindo) - Distribution of Highest Grade (I-V)	Approximately 30 to 45 days after hernia repair surgery, which would be approximately 2 to 3 months after injection procedure.	Highest complication grade based on the Clavien-Dindo classification system per participant within 30 days. "How measured": graded in REDCap from clinical documentation; unit = participants in each grade (%). Minimum = I, maximum = V; higher grades = worse.
90-Day SSI - Proportion of Participants (%)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Any incisional or organ/space infection within 90 days, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
90-Day SSOPI - Proportion of Participants (%)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 90 days. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).
90-Day Complication Severity (Clavien-Dindo) - Distribution of Highest Grade (I-V)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Highest complication grade based on the Clavien-Dindo classification system per participant within 90 days. "How measured": graded in REDCap from clinical documentation; unit = participants in each grade (%). Minimum = I, maximum = V; higher grades = worse.
90-Day Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).
1-Year SSOPI - Proportion of Participants (%)	Approximately 1 year after hernia repair surgery	These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 1 year. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).
90-Day Readmission - Proportion of Participants (%)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Any inpatient hospital readmission within 30 days of index surgery. "How measured": EHR review/REDCap; unit = participants (%).
1-Year Reoperation	Approximately 1 year after hernia repair surgery	Any return to the operating room related to the index surgery within 1 year. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).
90-Day Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Intensity Short Form 3a - T-Score (Raw Response score range: 0-10, Higher = Worse Pain)	Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.	Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.
1-Year Surgical Site Occurrence (SSO) - Proportion of Participants (%)	Approximately 1 year after hernia repair surgery	SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 1 year of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
1-Year Surgical Site Infection (SSI) - Proportion of Participants (%)	Approximately 1 year after hernia repair surgery	Any incisional or organ/space infection within 1 year, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
1-Year Reoperation for Hernia Recurrence	Approximately 1 year after hernia repair surgery	Any return to the operating room related repair of a hernia within 7 cm of the hernia repaired in the original surgery within 1 year. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).
1-Year Hernia Recurrence (Clinical)	Approximately 1 year after hernia repair surgery	A recurrence after hernia repair is defined as a new hernia detected within 7cm of the original repair. The hernia must be determined via imaging (ultrasound, computed tomography scan, or magnetic resonance imaging scan) or the documented physical exam of a licensed practitioner. Determined as within 1 year of the hernia repair surgery.
1-Year Hernia Recurrence (Patient-Reported)	Approximately 1 year after hernia repair surgery	Patient self-reported concern for recurrence based on response to the the question, "Do you feel or see a bulge?" on the Ventral Hernia Recurrence Inventory (VHRI) questionnaire. Asked at 1 year.
1-Year Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Intensity Short Form 3a - T-Score (Raw Response score range: 0-10, Higher = Worse Pain)	Approximately 1 year after hernia repair surgery	Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.
1-Year Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)	Approximately 1 year after hernia repair surgery	12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).
2-Year Surgical Site Occurrence (SSO) - Proportion of Participants (%)	Approximately 2 years after hernia repair surgery	SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 2 years of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
2-Year Surgical Site Infection (SSI) - Proportion of Participants (%)	Approximately 2 years after hernia repair surgery	Any incisional or organ/space infection within 2 years, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).
2-Year SSOPI - Proportion of Participants (%)	Approximately 2 years after hernia repair surgery	These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 2 years. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).
2-Year Reoperation	Approximately 2 years after hernia repair surgery	Any return to the operating room related to the index surgery within 2 years. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).
2-Year Reoperation for Hernia Recurrence	Approximately 2 years after hernia repair surgery	Any return to the operating room related repair of a hernia within 7 cm of the hernia repaired in the original surgery within 2 years. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).
2-Year Hernia Recurrence (Clinical)	Approximately 2 years after hernia repair surgery	A recurrence after hernia repair is defined as a new hernia detected within 7cm of the original repair. The hernia must be determined via imaging (ultrasound, computed tomography scan, or magnetic resonance imaging scan) or the documented physical exam of a licensed practitioner. Determined as within 2 years of the hernia repair surgery.
2-Year Hernia Recurrence (Patient-Reported)	Approximately 2 years after hernia repair surgery	Patient self-reported concern for recurrence based on response to the the question, "Do you feel or see a bulge?" on the Ventral Hernia Recurrence Inventory (VHRI) questionnaire. Asked at 2 years.
2-Year Patient-Reported Outcomes Measurement Information System (PROMIS®) Pain Intensity Short Form 3a - T-Score (Raw Response score range: 0-10, Higher = Worse Pain)	Approximately 2 year after hernia repair surgery	Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.
2-Year Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)	Approximately 2 year after hernia repair surgery	12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).

Trial Locations

Locations (1)

Cleveland Clinic Main Campus; 🇺🇸 Cleveland, Ohio, United States