PREoperative Targeted OnabotulinumtoXina Injection for Abdominal Wall Reconstruction: A Randomized, Double-Blind, Placebo-Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 188
- 试验地点
- 1
- 主要终点
- Primary Fascial Closure (PFC) at conclusion of Hernia Surgery (Yes / No, determined by surgeon)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Patients will be blinded to the intervention drug (botulinumtoxin vs placebo). Radiologist(s) performing the injection will be blinded to the intervention drug.
Surgeon(s) performing the hernia repair will be blinded to the intervention drug.
Only study personnel and pharmacists who are not participating in a patient's surgery will know the randomization group (intervention or placebo).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
OnabotulinumtoxinA Group
These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
干预措施: OnabotulinumtoxinA Injection (Procedure)
OnabotulinumtoxinA Group
These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
干预措施: OnabotulinumtoxinA (Drug)
OnabotulinumtoxinA Group
These patients will receive image-guided botulinumtoxin injections as described 21-48 days prior to open ventral hernia repair.
干预措施: Open Ventral Hernia Repair (Procedure)
Placebo Group
These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.
干预措施: Saline (placebo) Injection (Procedure)
Placebo Group
These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.
干预措施: 0.9 % Normal Saline (Drug)
Placebo Group
These patients will receive image-guided saline (placebo) injections as described 21-48 days prior to open ventral hernia repair.
干预措施: Open Ventral Hernia Repair (Procedure)
结局指标
主要结局
Primary Fascial Closure (PFC) at conclusion of Hernia Surgery (Yes / No, determined by surgeon)
时间窗: 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.
次要结局
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 90-Day Reoperation - Proportion of Participants (%)(Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 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.)
- 90-Day SSO - Proportion of Participants (%)(Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.)
- 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.)
- 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.)
- 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.)
- 90-Day SSI - Proportion of Participants (%)(Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.)
- 90-Day SSOPI - Proportion of Participants (%)(Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.)
- 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.)
- 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.)
- 1-Year SSOPI - Proportion of Participants (%)(Approximately 1 year after hernia repair surgery)
- 90-Day Readmission - Proportion of Participants (%)(Approximately 3 months after hernia repair surgery, which would be about 4 to 5 months after injection procedure.)
- 1-Year Reoperation(Approximately 1 year after hernia repair surgery)
- 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.)
- 1-Year Surgical Site Occurrence (SSO) - Proportion of Participants (%)(Approximately 1 year after hernia repair surgery)
- 1-Year Surgical Site Infection (SSI) - Proportion of Participants (%)(Approximately 1 year after hernia repair surgery)
- 1-Year Reoperation for Hernia Recurrence(Approximately 1 year after hernia repair surgery)
- 1-Year Hernia Recurrence (Clinical)(Approximately 1 year after hernia repair surgery)
- 1-Year Hernia Recurrence (Patient-Reported)(Approximately 1 year after hernia repair surgery)
- 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)
- 1-Year Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)(Approximately 1 year after hernia repair surgery)
- 2-Year Surgical Site Occurrence (SSO) - Proportion of Participants (%)(Approximately 2 years after hernia repair surgery)
- 2-Year Surgical Site Infection (SSI) - Proportion of Participants (%)(Approximately 2 years after hernia repair surgery)
- 2-Year SSOPI - Proportion of Participants (%)(Approximately 2 years after hernia repair surgery)
- 2-Year Reoperation(Approximately 2 years after hernia repair surgery)
- 2-Year Reoperation for Hernia Recurrence(Approximately 2 years after hernia repair surgery)
- 2-Year Hernia Recurrence (Clinical)(Approximately 2 years after hernia repair surgery)
- 2-Year Hernia Recurrence (Patient-Reported)(Approximately 2 years after hernia repair surgery)
- 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)
- 2-Year Hernia-Related Quality-of-Life Survey (HerQLes) - Score (0-100; Higher = Better QoL)(Approximately 2 year after hernia repair surgery)
研究者
Lucas Beffa
Assistant Professor of Surgery
The Cleveland Clinic