Clinical trial NCT02523599: Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty
Official title: A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy and Safety of the XaraColl® Bupivacaine Implant (300 mg Bupivacaine Hydrochloride) After Open Laparotomy Hernioplasty
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pain, Postoperative
Keywords: post operative pain
hernioplasty
bupivacaine
Lead sponsor: Innocoll
Sponsor class: INDUSTRY
First posted: 2015-08-14
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled efficacy and safety study of postoperative pain in adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy (tension-free technique).

Patients will assess their postoperative pain intensity (PI) using an 11-point numerical rating scale (NRS) from 0 hour through 72 hours postoperatively.

The expected maximum study duration for each patient will be up to 60 days, including a maximum 30-day screening period, the day of surgery and implantation, and a 30-day post implantation period including treatment and follow-up.

Detailed description: This is a Phase 3, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in adults who are scheduled for unilateral inguinal hernioplasty via open laparotomy (tension-free technique). Patients will receive either 3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose; or 3 placebo-sponges.

Three test article sponges will be implanted according to the patient's blinded treatment assignment. Following surgery, patients will be transferred to a postanesthesia care unit (PACU) and/or other postoperative recovery area for observation where they may receive parenteral morphine as needed (rescue medication for breakthrough pain) and on request for pain control. Once patients can tolerate oral medication, they will commence a standardized oral analgesic regimen with additional PRN medication to manage breakthrough pain only when it occurs.

Patients will assess their postoperative pain intensity (PI) using an 11-point numerical rating scale (NRS) from 0 hour through 72 hours postoperatively.

Patients will be observed postoperatively for a minimum of 3 hours and may be discharged at any time following completion of their 3-hour vital sign and PI assessments. Patients will be contacted at approximately 6, 24 and 48 hours after implantation to ensure protocol compliance and to perform safety assessments (including AEs and concomitant medications). At 72 hours, patients will return to the clinic to perform their final PI assessment, complete a categorical assessment of their overall pain control, and for follow-up safety assessments. They will also be asked to record the incidence of any ongoing or subsequent AEs (and any associated treatment) through Day 7. Additional follow-up assessments for safety will be performed at postoperative Day 7 (telephone call) and Days 15 and 30 (clinic visits).

Eligibility criteria: Inclusion Criteria:

* Has a planned (non-emergent) unilateral inguinal hernioplasty (open laparotomy, tension-free technique) to be performed according to standard surgical technique under general anesthesia. Repair of multiple hernias through a single incision is permitted provided only a single mesh will be used.
* If female, is nonpregnant and nonlactating.
* If female, is either not of childbearing potential (defined as postmenopausal for ≥ 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy or hysterectomy\]) or practicing 1 of the protocol specified medically-acceptable methods of birth control and agrees to continue with the regimen throughout the duration of the study:
* Has the ability and willingness to comply with the study procedures and use of the eDiary.
* Is willing to use only permitted medications throughout the study.
* Is willing to use opioid analgesia.
* Must be able to fluently speak and understand either English or Spanish and be able to provide meaningful written informed consent for the study.

Exclusion Criteria:

* Has a known hypersensitivity to amide local anesthetics, morphine, acetaminophen or bovine products.
* Is scheduled for bilateral inguinal hernioplasty or other significant concurrent surgical procedures per investigator discretion.
* Has undergone major surgery within 3 months of the scheduled hernioplasty or plans to undergo another laparotomy procedure within 30 days postoperatively.
* Has used any analgesic other than acetaminophen within 24 hours of surgery. Acetaminophen may be used on the day of surgery but is 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 before Screening.
* Has used systemic steroids, anticonvulsants, antiepileptics, antidepressants for the management of chronic pain, or monoamine oxidase inhibitors on a regular basis within 10 days of surgery.
* Has used any opioid analgesic for an extended daily basis (30 - 60 mg oral morphine equivalent per day for 3 or more days a week) within 4 weeks before surgery. Patients who, in the investigator's opinion, may be developing opioid tolerance are also excluded.
* Has any chronic painful condition (eg, fibromyalgia) or routinely uses pain medication other than acetaminophen (including nonsteroidal anti-inflammatory drugs \[NSAIDs\]) that, in the opinion of the investigator, may confound the assessment of pain associated with the hernioplasty.
* Has a physical or mental condition that, in the opinion of the investigator, may confound the assessment of postoperative pain after hernioplasty.
* Shows evidence of tolerance or physical dependency on opioid analgesics or sedative-hypnotic medications.
* Has a urine drug screen that tests positive for drugs of abuse or misuse, including cannabinoids.
* Has liver function test results greater than 3x the upper limit of normal or a history of cirrhosis.
* Has any clinically significant unstable cardiac disease (eg, uncontrolled hypertension, clinically significant arrhythmia at baseline, or an implantable cardioverter-defibrillator \[ICD\])
* Has any clinically significant unstable neurological, immunological, renal, or hematological disease (eg, uncontrolled diabetes or significantly abnormal laboratory findings), or any other condition that, in the opinion of the investigator, could compromise the patient's welfare, ability to communicate with the study staff or otherwise contraindicate study participation.
* Has an open workman's compensation claim.
* Has participated in a clinical trial (investigational or marketed product) within 30 days of surgery.

Primary outcomes:
measure: SPI24
timeFrame: 0 to 24 hours
Secondary outcomes:
measure: TOpA24
timeFrame: Time 0 through 24 hours
measure: TOpA48
timeFrame: Time 0 through 48 hours
measure: TOpA72
timeFrame: Time 0 through 72 hours
measure: SPI48
timeFrame: 0 to 48 hours
measure: SPI72
timeFrame: 0 to 72 hours
Other outcomes:
Locations:
city: Mobile
country: United States
state: Alabama
city: Sheffield
country: United States
state: Alabama
city: Phoenix
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Encino
country: United States
state: California
city: Bradenton
country: United States
state: Florida
city: Clermont
country: United States
state: Florida
city: Inverness
country: United States
state: Florida
city: Kissimmee
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Orlando
country: United States
state: Florida
city: Saint Petersburg
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Weston
country: United States
state: Florida
city: Indianapolis
country: United States
state: Indiana
city: Springfield
country: United States
state: Massachusetts
city: Flint
country: United States
state: Michigan
city: Las Vegas
country: United States
state: Nevada
city: Las Vegas
country: United States
state: Nevada
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Lampasas
country: United States
state: Texas
Study officials:
affiliation: Innocoll
name: Gwendolyn Niebler, D.O.
role: STUDY_DIRECTOR
References:
citation: Velanovich V, Rider P, Deck K, Minkowitz HS, Leiman D, Jones N, Niebler G. Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials. Adv Ther. 2019 Jan;36(1):200-216. doi: 10.1007/s12325-018-0836-4. Epub 2018 Nov 22.