Phase 4, Controlled Study in Adult Subjects Undergoing Primary, 1-2 Level, Open Lumbar Spinal Fusion Surgery
Paraules clau
Resum
Descripció
This is a Phase 4, multicenter, randomized, double-blind, controlled study in approximately 220 adult subjects undergoing primary, 1-2 level, open lumbar spinal fusion surgery under general anesthesia.
Subjects will be screened within 30 days prior to study drug administration and at least one day prior to surgery. During the screening visit, subjects will be assessed for past or present neurologic, cardiac, and general medical conditions that in the opinion of the Investigator would preclude them from study participation. After the informed consent form (ICF) is signed, a medical history, surgical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, select clinical laboratory evaluations, urine drug screen, alcohol breath test, and urine pregnancy test for women of childbearing potential will be conducted. Study drug, approximately 1-2 mL every 1.0-1.5 cm, will be administered using 20- or 22-gauge needles prior to wound closure.
Administration Instructions/Procedures
Study drug should be injected in the prescribed locations based on the areas of highest nerve density. Study drug will be administered using syringes with 20- or 22-gauge needles prior to wound closure. The Investigator must document the size of the incision. Each infiltration site should be spaced 1.0-1.5 cm apart and should deliver approximately 1-2 mL into both deep and superficial areas (para-spinous fascia, muscle, and subcutaneous layers). Total volume administered will be depended on the number of levels of dissection, as described below. Following infiltration, the tissue should visibly expand with minimal leakage.
Total Volume of Expansion
The Investigator must document the total volume used for each surgery.
1. Level Procedures Group 1: EXPAREL 266 mg in 20 mL + bupivacaine HCl 0.5% in 20 mL + 20 mL normal saline = total volume of 60 mL Group 2: Bupivacaine HCl 0.5% in 20 mL + 40 mL normal saline = total volume of 60 mL
2. Level Procedures Group 1: EXPAREL 266 mg in 20 mL + bupivacaine HCl 0.5% in 20 mL + 50 mL normal saline = total volume of 90 mL Group 2: Bupivacaine HCl 0.5% in 20 mL + 70 mL normal saline = total volume of 90 mL
Drains may be used at the surgeon's discretion. In addition to LIA, all study participants will receive a standardized approach for managing postsurgical pain that includes a scheduled multimodal pain regimen including adjunctive analgesics, non-steroidal anti-inflammatory drugs (NSAIDs). Rescue analgesics will be available as needed.
Postsurgical clinical assessments will include pain intensity scores using a 10-cm visual analog scale (VAS) (see Appendix 1); overall benefit of analgesia score (OBAS) questionnaire (see Appendix 2); total postsurgical opioid consumption; predefined opioid-related AEs; and nurse's satisfaction with overall analgesia (see Appendix 3).
Adverse events will be recorded from the time the ICF is signed through Day 30. If a cardiac AE (e.g., chest pain [angina, myocardial infarction], abnormal/irregular heart rate [bradycardia, tachycardia, extrasystoles], or shortness of breath), neurological AE (e.g., altered mental status/altered sensorium, dizziness, dysarthria, hyperesthesia, metallic taste, peroral numbness, seizure, tinnitus, tremors, visual disturbance, muscular twitching or rigidity beyond 72 hours postdose, or tingling/paresthesia beyond 72 hours postdose), or serious AE (SAE) occurs during the study a 12-lead ECG, vital signs, and any appropriate clinical laboratory tests should be conducted.
Postsurgical health economic outcome assessments will include hospital length of stay (LOS), use of skilled nursing facility, hospital readmissions, and use of other health services following discharge (phone calls related to postsurgical pain, unscheduled visits related to postsurgical pain, and visits to emergency department) through Day 30.
A follow-up visit will be scheduled for all subjects on postsurgical Day 14. A follow-up phone call will be made on Day 30 to all subjects who received study drug to assess for adverse events (AEs).
Number of Subjects (Planned):
Approximately 194 subjects are planned for enrollment in this study in order to have at least 184 evaluable subjects.
Dates
| Darrera verificació: | 11/30/2017 |
| Primer enviat: | 11/13/2016 |
| Inscripció estimada enviada: | 01/05/2017 |
| Publicat per primera vegada: | 01/09/2017 |
| Última actualització enviada: | 12/06/2017 |
| Publicació de l'última actualització: | 12/10/2017 |
| Data d'inici de l'estudi real: | 10/31/2016 |
| Data estimada de finalització primària: | 08/31/2017 |
| Data estimada de finalització de l’estudi: | 08/31/2017 |
Condició o malaltia
Intervenció / tractament
Drug: Bupivacaine HCl
Drug: EXPAREL admixed with bupivacaine HCl
Fase
Grups de braços
| Braç | Intervenció / tractament |
|---|---|
| Active Comparator: EXPAREL admixed with bupivacaine HCl | Drug: EXPAREL admixed with bupivacaine HCl Drug: EXPAREL EXPAREL and bupivacaine HCl
Other Name: bupivacaine liposome injectable suspension Drug: Bupivacaine Single dose of bupivacaine HCl 0.5%
Other Name: bupivacaine HCl |
| Placebo Comparator: bupivacaine HCl |
Criteris d'elegibilitat
| Edats elegibles per estudiar | 18 Years Per a 18 Years |
| Sexes elegibles per estudiar | All |
| Accepta voluntaris saludables | Sí |
| Criteris | Inclusion Criteria: 1. Male or female, at least 18 years of age at screening. 2. Primary surgical indication is lumbar pain, radiculopathy, disc degeneration, disc herniation, foraminal stenosis, or 1-2 level spondylolisthesis or deformity. 3. Scheduled to undergo primary, 1-2 level, open spine fusion under general anesthesia. 4. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3. 5. Female subjects must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, or transdermal, contraceptive approved by the FDA for greater than 2 months prior to screening. All women of childbearing potential (ie, premenopausal without permanent sterilization) must commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study. 6. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments Exclusion Criteria: 1. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. 2. Serious spinal conditions (to include cauda equina syndrome, infection, tumor, fracture, or severe osteoporosis [i.e., if taking Bisphosphonate or TNF-α blockers]). 3. Previous spinal surgery at the same level other than microdiscectomy (e.g., laminectomy, fusion). 4. Planned concurrent surgical procedure. 5. Identification of a dural tear during surgery will be an intra-operative exclusion unless it is well repaired (no evidence of CSF leak with Valsalva and no plan to restrict activity post-operatively). Any injury to the nerve root occurring during surgery will also be considered an intra-operative exclusion. 6. Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the spinal surgery and which may confound the postsurgical assessments. 7. Comorbidity impacting current physical function or Investigator opinion that it may impact postsurgical rehabilitation. 8. Allergy, hypersensitivity, or contraindication to any of the study medications (i.e., bupivacaine, oxycodone, morphine, hydromorphone, gabapentin, acetaminophen, celecoxib, or cyclobenzaprine) for which an alternative medication is not provided in the protocol. 9. Use of any of the following medications within the times specified before surgery: long-acting opioid medication (eg, morphine including MS Contin®, hydromorphone [Dilaudid®], oxycodone [Oxycontin®], methadone) daily for more than 3 months duration or within 3 days of surgery or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours. Patients receiving short-acting opioids or NSAIDs should be at a steady or plateau dose. Such patients should require or receive no more than 20 morphine equivalents (eg, 4 Percocet) within 24 hours of surgery. 10. Initiation of treatment with any of the following medications within 1 month of study drug administration or if the medication(s) are being given to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), or duloxetine (Cymbalta). If a subject is taking one of these medications for a reason other than pain control, he or she must be on a stable dose for at least 1 month prior to study drug administration. Gabapentin (Neurotin) or pregabalin (Lyrica) is permitted pre-operatively if the duration has been less than 12 weeks. 11. Current use of systemic glucocorticosteroids within 1 month of enrollment in this study. 12. Use of dexmedetomidine HCl (Precedex) within 3 days of study drug administration. 13. History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion). 14. Have been treated for a deep vein thrombosis, pulmonary embolism, myocardial infarction, or ischemic stroke within the past 6 months (may be extended to 1 year if medically indicated per physician discretion). 15. Severely impaired renal (e.g., serum creatinine clearance ≤ 30) or hepatic function (e.g., serum AST level >3 x ULN or serum ALT level >3 x ULN). 16. Any neurologic or psychiatric disorder that might impact postsurgical pain or interfere with study assessments. 17. Malignancy in the last 2 years, per physician discretion. 18. History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol. Dependence or chronic opioid use will be defined as use of more than 30 morphine equivalents per day during the prior 90 days. 19. Failure to pass the urine drug screen or alcohol breath test. 20. Body weight <50 kg (110 pounds) or a body mass index >40 kg/m2. 21. Subjects receiving Worker's compensation for a disability or who are involved in litigation. 22. Previous participation in an EXPAREL study. 23. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study |
Resultat
Mesures de resultats primaris
1. The AUC of the VAS pain intensity scores from 12-48 hours [12-48 hours]
Mesures de resultats secundaris
1. Proportion of subjects who are pain free (defined as a VAS pain intensity score of ≤1.5 and no prior rescue medication) at each assessed timepoint [72 hours]
2. The AUC of the VAS pain intensity scores through 24, 36, 48, 60, and 72 hours [72 hours]
3. The AUC of the VAS pain intensity scores from 24-48 and 48-72 hours [72 hours]
4. The sum of the pain intensity scores (SPIS) through 24, 48, and 72 hours [72 hours]
5. SPIS from 24-48 and 48-72 hours [72 hours]
6. Total inpatient postsurgical opioid consumption (in mg) through 24 and 72 hours and hospital discharge [72 hours]
7. Total postsurgical opioid consumption (in mg) from hospital discharge through Day 30 [30 days]
8. Percentage of opioid-free subjects through 24, 48, and 72 hours or hospital discharge [72 hours]
9. Time to first opioid rescue through 72 hours or hospital discharge [72 hours]
10. Incidence of the following opioid-related AEs until the discharge order is written: respiratory depression, hypoventilation, hypoxia, dry mouth, nausea, vomiting, constipation, altered mental status, pruritus, urinary retention, and postoperative ileus [30 days]
11. The OBAS total score at 24, 48, and 72 hours [72 hours]
12. Pain interference at Day 1 Pre-op and Day 14 [14 Days]
13. Nurse's satisfaction with overall analgesia at 24, 48, and 72 hours or upon hospital discharge [72 hours]
14. total opioid consumption (in IV morphine equivalents) from 0-48 hours [48 hours]
