Pain, PostoperativePhase 3MATRIX-2NCT02525133
Phase 3 Study of Efficacy and Safety of the XaraColl® Bupivacaine Implant After Hernioplasty
A Phase 3 study testing XaraColl in people with Pain, Postoperative, run by Innocoll at 24 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Postoperative
- What is being tested?
- XaraColl
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 319 participants
- Where
- 24 sitesUnited States
- Study dates
- 5 Sep 2015to 22 Apr 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
United States24 sites
Study site
Anaheim, California, 92801
Study site
Anniston, Alabama, 36207
Study site
Aurora, Colorado, 80045
Study site
Birmingham, Alabama, 35216
Study site
Chicago, Illinois, 60645
Study site
Cleveland, Ohio, 44106
Study site
Columbus, Georgia, 31904
Study site
Columbus, Ohio, 43210
Study site
Durham, North Carolina, 27710
Study site
Houston, Texas, 77004
Study site
Houston, Texas, 77024
Study site
Laguna Hills, California, 92653
Study site
Las Vegas, Nevada, 89104
Study site
Madison, Wisconsin, 53792
Study site
Miami, Florida, 33134
Study site
Miami, Florida, 33155
Study site
Newport News, Virginia, 23606
Study site
Oklahoma City, Oklahoma, 73104
Study site
Pasadena, California, 91105
Study site
Pembroke Pines, Florida, 33028
Study site
Pensacola, Florida, 32503
Study site
Philadelphia, Pennsylvania, 19104
Study site
Placentia, California, 92870
Study site
Salt Lake City, Utah, 84124
About this study
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
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.
Read the 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).
- Conditions
- Pain, Postoperative
- Being tested
- XaraColl, Placebo
- Keywords
- post operative pain, hernioplasty, bupivacaine
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XaraCollDrug
Also called Bupivacaine collagen implant
Surgical implantation of 3 bupivacaine collagen implants
PlaceboOther
Also called Collagen implant
Plain collagen implant (vehicle)
| Study group | Role | What they receive |
|---|---|---|
| XaraColl | Experimental | 3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose Receives: Drug: XaraColl |
| Placebo | Placebo comparator | 3 placebo implants Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
SPI24
The primary efficacy variable (time-weighted sum of pain intensity from Time 0 through 24 hours [SPI24]) was compared once at a 2-sided 0.05 level. Therefore, no multiplicity adjustment was necessary for the primary efficacy analysis. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". Minimum value would be "0" and Maximum value would be 240. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑[PI x (time t - time t-1)], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Measured: 0 to 24 hours
Secondary outcomes (5)
TOpA24
Total use of opioid analgesia (TOpA) from Time 0 through 24 hours (TOpA24) This is a basic measurement of counting in total the number of morphine tablets (15 mg) patients had to use within a 24-hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Measured: Time 0 through 24 hours
TOpA48
Total use of opioid analgesia (TOpA) from Time 0 through 48 hours (TOpA48) This is a basic measurement of counting in total the number of morphine tablets (15 mg) patients had use within a 48-hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Measured: Time 0 through 48 hours
TOpA72
Total use of opioid analgesia (TOpA) from Time 0 through 72 hours (TOpA72) This is a basic measurement of counting in total the number of morphine tablets (15 mg) patients had use within a 72-hour period (typically called "rescue" to help manage pain. Zero (0) is the "lowest" score. The lower the number of tablets the better outcome.
Measured: Time 0 through 72 hours
SPI48
Time-weighted sum of pain intensity from Time 0 through 48 hours (SPI48). Lower score has a better outcome. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". Minimum value would be "0" and Maximum value would be 480. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI48 = ∑[PI x (time t - time t-1)], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Measured: 0 to 48 hours
SPI72
Time-weighted sum of pain intensity from Time 0 through 72 hours (SPI72) A lower score is a better outcome. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible" Minimum value would be "0" and Maximum value would be 720. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI72 = ∑[PI x (time t - time t-1)], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
Measured: 0 to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2015 (estimated)
- Study start5 Sep 2015
- Primary completion22 Apr 2016
- Study completion22 Apr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 319 participants (actual)
Sponsor and investigators
- Lead sponsor
- Innocoll
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gwendolyn Niebler, D.O., Study director, Innocoll
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02525133
- Sponsor's protocol ID
- INN-CB-016
- Acronym
- MATRIX-2
- Status last verified
- Jan 2021
- First submitted
- 12 Aug 2015
- Last updated
- 8 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 30467808
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02525133
- Acronym / sponsor ID
- MATRIX-2 / INN-CB-016
- Conditions
- Pain, Postoperative
- Keywords
- post operative pain, hernioplasty, bupivacaine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 319 participants (actual)
- Lead sponsor
- InnocollIndustry (pharma, biotech, devices)
- Study start
- 5 Sep 2015
- Primary completion
- 22 Apr 2016 (actual)
- Study completion
- 22 Apr 2016 (actual)
- First posted
- 17 Aug 2015 (estimated)
- Results
- Posted 8 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| XaraColl | Experimental | Drug: XaraColl3 XaraColl Bupivacaine Implants each containing 100 mg of bupivacaine hydrochloride, for a 300 mg total dose |
| Placebo | Placebo comparator | Other: Placebo3 placebo implants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XaraCollAlso: Bupivacaine collagen implantSurgical implantation of 3 bupivacaine collagen implants | Drug | XaraColl |
| PlaceboAlso: Collagen implantPlain collagen implant (vehicle) | Other | Placebo |
Primary outcome
SPI24
Time frame: 0 to 24 hours
The primary efficacy variable (time-weighted sum of pain intensity from Time 0 through 24 hours [SPI24]) was compared once at a 2-sided 0.05 level. Therefore, no multiplicity adjustment was necessary for the primary efficacy analysis. Pain Intensity was assessed by the subject using the 11-point NRS, where 0 indicated "no pain" and 10 indicated "worst pain possible". Minimum value would be "0" and Maximum value would be 240. Time-weighted SPI is calculated as the sum of the pain intensities between successive time points (i.e., if SPI24 = ∑[PI x (time t - time t-1)], where "t" represents a given time point,"t-1" represents the previous time point, and time is expressed in hours). This represents the AUC (Area Under the Curve) of the pain intensities when calculated with the trapezoidal rule.
5 secondary outcomes
TOpA24
Time frame: Time 0 through 24 hours
TOpA48
Time frame: Time 0 through 48 hours
TOpA72
Time frame: Time 0 through 72 hours
SPI48
Time frame: 0 to 48 hours
SPI72
Time frame: 0 to 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30467808Velanovich 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gwendolyn Niebler, D.O. study director
Innocoll
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing XaraColl in people with Pain, Postoperative, run by Innocoll at 24 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SPI24 (time frame: 0 to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02525133, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2021.