Efficacy and Safety of the CollaRx Bupivacaine Implant Compared to the ON-Q Painbuster Following Abdominal Hysterectomy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the CollaRx Bupivacaine Implant is safe and effective in reducing the amount of narcotic pain medication needed to control pain during the first 96 hours after abdominal hysterectomy when compared to the ON-Q PainBuster Post-op Pain Relief System.

Detailed Description
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Hysterectomy is the second most common surgery among women in the United States (US). Abdominal hysterectomy surgery may be performed to treat benign tumors, such as fibroids, heavy periods, painful periods and chronic pelvic pain. The most common route for performing hysterectomy is through an incision in the abdominal wall; however, about 20% are performed vaginally.Laparoscopic assisted vaginal hysterectomy is performed when warranted. Bupivacaine is a local anesthetic (pain medication) 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 cattle 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. The ON Q system consists of 1 elastometric pump with a fill volume of 270 mL containing 0.25% bupivacaine; 1 soaker catheter measuring 12.5 cm in size; and a fill port, tubing, clamp, filter and flow restrictor. The pump provides positive pressure and is portable. It may be attached to the patient's dressing or placed in a carrying pouch. The catheter is inserted directly into the surgical wound providing a continuous flow of bupivacaine into the wound. A capillary flow restricting orifice located at the end of the tubing controls the flow rate. This study will compare the total narcotic use in patients with the CollaRx Bupivacaine Implant with the total narcotic use in patients with the ON Q PainBuster Post op Pain Relief System after abdominal hysterectomy.

Official Title
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A Phase II, Randomized, Single-dose, Unblinded Study to Compare the Efficacy and Safety of the CollaRx Bupivacaine Implant With the ON-Q PainBuster Post-op Pain Relief System in Women Following Abdominal Hysterectomy

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Bupivacaine Collagen Sponge (CollaRx Bupivacaine Implant)
* Drug: ON-Q PainBuster Post-op Pain relief System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be a woman who is ≥ 18 and ≤ 75 years of age. Has a body mass index (BMI) > 19 and < 40 kg/m2. Has planned an elective total abdominal hysterectomy for reasons other than malignancies (such as uterine adenocarcinoma, cervical cancer or leiomyosarcoma) to be performed according to standard surgical technique using a standard incision and under general anesthesia with the following caveats: Laparoscopic procedures or supraumbilical or Maylard incisions will not be allowed. A nonlaparoscopic incision for benign nonhysterectomy gynecological procedures (such as myomectomy or adnexal surgery) is acceptable if the surgical indication is not to treat pelvic pain. No concomitant vaginal procedures such as anterior and posterior colporrhaphy (A&P repairs) are allowed. An abdominal urethropexy and an incidental appendectomy will be allowed. Has a risk classification of I, II or III according to the American Society of Anesthesiologists (ASA). Is nonpregnant (negative pregnancy test at Screening and Day 0 before surgery) and nonlactating. Is free of other physical or mental conditions that, in the opinion of the Investigator, may confound quantification of postoperative pain resulting from the abdominal hysterectomy. Has the ability to read, understand and comply with the study procedures and the use of the pain scales; is deemed capable of operating a patient controlled analgesia (PCA) device; and is able to communicate meaningfully with the study staff. Must voluntarily sign and date an informed consent form (ICF), approved by an Institutional Review Board (IRB), prior to the conduct of any study specific procedures. Must be able to fluently speak and understand English and be able to provide meaningful written informed consent for the study. Exclusion Criteria: Has known hypersensitivity to amide local anesthetics, opioids, bovine products or to inactive ingredients of the test article or reference product. Has cardiac arrhythmias or atrioventricular (AV) conduction disorders. Concomitantly uses other amide local anesthetics. Concomitantly uses antiarrhythmics (eg, amiodarone), propranolol or strong/moderate cytochrome P450 (CYP) 3A4 inhibitors or inducers (eg, macrolide antibiotics and grapefruit juice). Has 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. Has used aspirin or aspirin containing products within 7 days of surgery. Aspirin at a dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the patient has been on a stable dose regimen for ≥ 30 days prior to Screening. Has undergone major surgery within 3 months of the scheduled hysterectomy. Requires the use of Seprafilm® or other absorbable adhesion barriers for the scheduled hysterectomy. Requires any additional surgical procedures either related or unrelated to the abdominal hysterectomy during the same hospitalization (except for the specific allowed procedures noted in the Inclusion Criteria). Is required to receive neuraxial (spinal or epidural) opioid analgesics during the surgery. Has known or suspected history of alcohol or drug abuse or misuse within 3 years of Screening or evidence of tolerance or physical dependency on opioid analgesics or sedative hypnotic medications. Has used opioids or tramadol on an extended daily basis (> 7 days) prior to surgery. Patients who, in the Investigator's opinion, are developing opioid tolerance are to be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bupivacaine collagen sponge<br>Three Bupivacaine sponges placed at different levels within the surgical cavity; one deep within the vault, one at the incision line in the peritoneum and one at the dermal incision line. | Drug: Bupivacaine Collagen Sponge (CollaRx Bupivacaine Implant)<br>* The bupivacaine collagen sponge contains 70mg Type I bovine collagen and 50mg bupivacaine hydrochloride<br>* Other names: CollRx Bupivacaine Implant;|
| Active Comparator: ON-ON-Q PainBuster Post-op Pain relief SystemQ system<br>Insertion of the ON-Q system catheter into the deep subcutaneous space overlying the fascia. | Drug: ON-Q PainBuster Post-op Pain relief System<br>* 5 mL/hr per catheter of 0.25% bupivacaine (12.5 mg) for 72 hours(total dose 360 mL [900 mg])<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Amount of Opioid Rescue Analgesia Used | Higher value means worse outcome - Higher number reflects a need for more analgesia - For the first 24 hours after surgery, patients received IV morphine via a PCA pump as rescue analgesia. Patient demand for morphine was recorded. Measurement recorded in total Morphine Milligrams | 0 to 24 hours postoperatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Amount of Opioid Rescue Analgesia Used | Higher score means worse outcome - Higher number means more Analgesia was needed. For the first 24 hours after surgery, patients received IV morphine via a PCA pump as rescue analgesia. Patient demand for morphine was recorded. After 24 hours, patients were offered hydrocodone/acetaminophen (maximum could not exceed 8 tablets per 24 hours of the 5/500 mg tablets [40 mg hydrocodone and 4000 mg acetaminophen]) or similar medication as determined by the Investigator for pain until discharge. If oral medication was insufficient for control of pain, IM or IV morphine could be administered. | 0 to 48 hours postoperatively | 
| The Total Amount of Opioid Rescue Analgesia Used | Higher score means worse outcome. Higher number means more Analgesia was needed. For the first 24 hours after surgery, patients received IV morphine via a PCA pump as rescue analgesia. Patient demand for morphine was recorded. After 24 hours, patients were offered hydrocodone/acetaminophen (maximum could not exceed 8 tablets per 24 hours of the 5/500 mg tablets [40 mg hydrocodone and 4000 mg acetaminophen]) or similar medication as determined by the Investigator for pain until discharge. If oral medication was insufficient for control of pain, IM or IV morphine could be administered. | 0 to 96 hours postoperatively | 
| Total Use of Opioid Rescue Analgesia (mg) Over 0 to 72 Hours | Higher score means worse outcome. Higher number means more Analgesia was needed. For the first 24 hours after surgery, patients received IV morphine via a PCA pump as rescue analgesia. Patient demand for morphine was recorded. After 24 hours, patients were offered hydrocodone/acetaminophen (maximum could not exceed 8 tablets per 24 hours of the 5/500 mg tablets [40 mg hydrocodone and 4000 mg acetaminophen]) or similar medication as determined by the Investigator for pain until discharge. If oral medication was insufficient for control of pain, IM or IV morphine could be administered. | 0 to 72 Hours | 
| Time to First Use of Opioid Rescue Analgesia | Higher score has a better outcome | 0 to 72 hours | 
| VAS Pain Intensity Scores Over Time AT REST | For the VAS assessment, patients measured their pain intensity at rest using a horizontal 100-mm VAS scale labeled as follows: No Pain (0 mm) as the left anchor and Worst Pain Imaginable (100 mm) as the right anchor. | Hour 1, 1.5, 2,3,6,9,12,18,24,36,48,72,96 | 
| VAS (mm) Pain Intensity Scores Over Time (After Cough) | For the VAS assessment, patients measured their pain intensity after aggravated movement (cough) using a horizontal 100-mm VAS scale labeled as follows: No Pain (0 mm) as the left anchor and Worst Pain Imaginable (100 mm) as the right anchor. | Hour 1, 1.5, 2,3,6,9,12,18,24,36,48,72,96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Abdominal Hysterectomy, Postoperative pain