Safety and Efficacy of CollaRx® Bupivacaine Implant in Men After Open Laparotomy Herniorrhaphy

Study Overview
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Brief Summary
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This study will assess pain intensity for the first 72 hrs after after aggravated movement (cough)following open laparotomy inguinal herniorrhaphy in patient who receive either the CollaRx Bupivacaine implant or a plain collagen sponge.

Detailed Description
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Inguinal herniorrhaphy is a common surgery; and common surgical methods used include laparoscopic and open placement of synthetic mesh. The use of synthetic mesh can greatly reduce the risk of hernia recurrence regardless of the method used for its placement. Managing postoperative pain and preventing morbidity after open mesh herniorrhaphy remain considerable medical challenges. Bupivacaine is a local anesthetic (pain medicine) that has an established safety profile. Collagen is a protein that is found in all mammals. The CollaRx Bupivacaine implant is a thin flat sponge made out of collagen that comes from cow tendons and contains bupivacaine. When inserted into a surgical site, the collagen breaks down and bupivacaine is released at the site but very little is absorbed into the blood stream. The high levels of bupivacaine at the surgical site may result in less pain for several days after surgery. This study will assess pain intensity after surgery in patients who receive either the CollaRx Bupivacaine implant or a plain collagen sponge.

Official Title
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A Phase II, Randomized, Single Dose, Double-blind, Placebo Controlled Study to Investigate the Efficacy and Safety Profile of the CollaRx® Bupivacaine Implant (200 mg Bupivacaine Hydrochloride) in Men After Open Laparotomy Herniorrhaphy

Conditions
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Herniorrhaphy, Postoperative Pain, Inguinal Hernia

Intervention / Treatment
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* Drug: Bupivacaine Collagen Sponge
* Drug: Placebo collagen Sponge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man ≥ 18 years Body mass index (BMI) ≥ 19 and ≤ 40 kg/m2. Has a planned unilateral inguinal herniorrhaphy (open laparotomy, tension free technique) to be performed according to standard surgical technique under general anesthesia. Exclusion Criteria: Has a known hypersensitivity to amide local anesthetics, opioids, or bovine products. Scheduled for bilateral inguinal herniorrhaphy. Undergone a prior herniorrhaphy on the side scheduled for repair. Undergone major surgery within 3 mos of the scheduled herniorrhaphy. Has cardiac arrhythmias or atrioventricular (AV) conduction disorders. Concomitantly uses antiarrhythmics (eg, amiodarone, lidocaine), propranolol, or strong/moderate cytochrome P450 (CYP) 3A4 inhibitors or inducers (eg, macrolide antibiotics and grapefruit juice). Used long acting analgesics within 24 hours of surgery. Short acting analgesics such as acetaminophen may be used on the day of surgery but are subject to preoperative restrictions for oral intake.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2, 5x5cm bupivacaine collagen sponges<br>collagen sponges | Drug: Bupivacaine Collagen Sponge<br>* Drug: Bupivacaine Collagen Sponge<br>* Other names: Bupivacaine Implant;|
| Placebo Comparator: 2, Placebo collagen sponges<br>Placebo collagen sponges | Drug: Placebo collagen Sponge<br>* Drug: Placebo Collagen Sponge<br>* Other names: Collagen Implant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity Defined as Area Under the Curve (AUC) of 100-mm VAS PI Scores. | The primary efficacy variable was SPI defined as area under the curve (AUC) of 100-mm VAS pain intensity scores after aggravated movement (cough) from 1 to 72 hours after surgery. Minimum score is 0. Maximum score is 7200. This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule. A lower score means a better outcome or less pain reported. | 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of Pain Intensity (SPI) After Aggravated Movement (Cough) | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100) at each time point. A lower score is better which means the patient experience lower pain. The score is calculated using the number of hours * the VAS score. This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule. For each measure outcome - the minimum score is 0 and the maximum score is 100* the number of hours in that period. | 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours. | 
| Sum of Pain Intensity (SPI) Using a Visual Analog Scale (VAS) When at Rest | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100) at each time point. A lower score is better which means the patient experience lower pain. The score is calculated using the number of hours * the VAS score. This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule. For each measure outcome - the minimum score is 0 and the maximum score is 100* the number of hours in that period. | 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours. | 
| Pain Intensity Visual Analog Pain Scale Scores Over Time After Aggravated Movement (Cough) | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100). Patients were asked during multiple time points to provide a score on this VAS scale. The lower the sore the better the outcome. Higher score is a worse outcome | 1,2,4,6,8,10,12,24,48 and 72 hours | 
| Pain Intensity VAS Scores Over Time at Rest | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100). Patients were asked during multiple time points to provide a score on this VAS scale. Lower score is better. Higher score means more pain. Time points are summarized independently | 1,2,4,6,8,10,12,24,48 and 72 hours | 
| Mean Sum of Pain Intensity (SPI) Categorical Scores After Aggravated Movement | Measured on a Visual Analog Pain Scale (VAS) with the lowest possible value of 0 and highest 100 (0 - 100) for each timepoint. (timepoints 1,2,4,6,8,10,12,24,48 and 72 hours ) Patients were asked during multiple time points to provide a score on this VAS scale. For 1 to 24 hours the highest score possible would be 800. For 1 to 48 hours the highest score possible would be 900. For 1 to 72 hours the highest score possible would be 1000. A mean Lower score is better. A mean Higher score is a worse outcome. | 1,2,4,6,8,10,12,24,48 and 72 hours |