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.
Adult (greater than or equal to 18 years of age)
Candidate for elective open repair of ventral hernia
ventral hernia defect width of at lest 15 cm; AND/OR,
Tanaka volume ratio of at least 25%
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)
Parallel
OnabotulinumtoxinA Injection
Procedure/SurgeryA total of 300 units of onabotulinumtoxinA will be reconstituted 150 cc of injectable 0.9% NaCl (for a final concentration of 2 units / cc). Each side of the abdominal wall will receive a total 75 cc distributed across three injection sites (six injection sites total per patient). At each injection site, the muscle bodies of the transversus abdominis, internal oblique, and external oblique will receive an equivalent volume of product under ultrasonic or radiographic visualization.
Saline (placebo) Injection
Procedure/Surgery150 cc of injectable 0.9% NaCl will be prepared. Each side of the abdominal wall will receive a total 75 cc distributed across three injection sites. At each injection site, the muscle bodies of the transversus abdominis, internal oblique, and external oblique will receive an equivalent volume of product under ultrasonic or radiographic visualization.
OnabotulinumtoxinA
Drug300 units of onabotulinumtoxinA will be prepared and administered as described in: "Procedure/Surgery: OnabotulinumtoxinA Injections"
0.9 % Normal Saline
Drug150cc of normal saline will be prepared and administered as described in: "Procedure/Surgery: Saline (placebo) Injection".
Open Ventral Hernia Repair
Procedure/SurgeryOpen abdominal wall reconstruction will be conducted in our standard fashion for the repair of very large hernias. The surgery is the same for patients who are not in the study. Surgeons will be blinded to the study arm of participant patients.
Primary Fascial Closure (PFC) at conclusion of Hernia Surgery (Yes / No, determined by surgeon)
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.
30-Day Surgical Site Occurrence (SSO) - Proportion of Participants (%)
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 Surgical Site Infection (SSI) - Proportion of Participants (%)
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 SSOPI (Surgical Site Occurrence Requiring Procedural Intervention) - Proportion of Participants (%)
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 (%).
30-Day Readmission - Proportion of Participants (%)
Any inpatient hospital readmission within 30 days of index surgery. "How measured": EHR review/REDCap; unit = participants (%).
Fascial Tension (Pre-Release and Post-Component Separation) - Force Units (lbs)
Force required to bring each fascial edge to midline, measured twice: (1) after initial dissection/before retro-rectus release and (2) after each step during posterior component separation. "How measured": sterile Kocher clamps attached to fascia will be connected to a sterilizable tensiometers which is pulled until midline is reached by medial fascial edge; force recorded. Unit = pounds of force (lbs); higher values = greater tension.
Plateau Airway Pressure - cmH₂O
Ventilator plateau pressure measured (a) after intubation before incision, (b) just before skin closure (after repair), and (c) POD1 if still intubated. "How measured": volume-controlled ventilation; inspiratory pause 0.5-3 s; stabilized pressure recorded as Pplat; also record PIP, tidal volume, ventilator mode, PEEP, FiO₂. Unit = cmH₂O.
Change in Plateau Pressure With Closure - cmH₂O
Difference between pre-closure and post-closure plateau pressures; negative change indicates improved mechanics. "How measured": subtraction of time-point values. Unit = cmH₂O.
Bladder Pressure (Intra-abdominal Pressure Proxy) - mmHg
Measured three times for all patients: (1) after anesthesia before incision and (2) immediately pre-extubation; also (3) on POD1 prior to Foley removal. "How measured": per WSACS consensus - instill ≤25 mL sterile saline via stopcock into a clamped Foley; patient supine with bed flat; transduce at mid-axillary line at end-expiration. Unit = mmHg.
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The Cleveland Clinic
Lead sponsor
Joseph and Florence Mandel Family Foundation
Collaborator
