A Phase 4 interventional study of Liposomal bupivacaine injection and Bupivacaine indwelling catheter in Drug Effect, Rib Fractures and Rib Trauma, sponsored by Denver Health and Hospital Authority. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-09-29.
Sponsored by Denver Health and Hospital Authority · Phase 4, Interventional, and Treatment
Rib fractures represent a common injury pattern this is highly associated with patient morbidity and mortality, as pain control remains a challenge. Even after surgical stabilization of rib fractures (SSRF), unsuccessful pain control can lead to morbid outcomes such as pneumonia and opioid dependence. Multi-modal anesthesia, with the use of thoracic epidurals and para-vertebral injections/catheters, has shown to lessen these occurrences but are subject to a wide array of limitations. A more directed therapy with liposomal bupivacaine has shown to provide sustained analgesia for up to 72 hours in patients who have undergone other types of thoracic surgery, but not SSRF. The hypothesis of the current clinical trial is that, among patients undergoing SSRF, liposomal bupivacaine delivered via video assisted thoracic surgery (VATS) is an intercostal nerve block that provides comparable analgesia to the pain catheter, as measured by pulmonary function, numeric pain scoring, and postoperative narcotic use.
Rib fractures represent a common injury pattern with high associated morbidity and mortality. Effective pain control in both the acute and long term periods remains a challenge. Surgical stabilization of rib fractures (SSRF) is now a recommended treatment for patients with severe chest wall injuries. In addition to stabilization of the chest wall, SSRF offers a unique opportunity to deliver directed, loco-regional anesthesia. Loco-regional anesthesia is a recognized, essential component of multi-modal anesthesia for patients with rib fractures in order to both decrease pain and minimize the use of opioids and their associated side effects.
Delivery options for loco-regional anesthesia to patients with rib fractures share in common the intention of anesthetizing the intercostal nerves. Moving from the spinal cord laterally, modalities include thoracic epidural catheters, paravertebral blocks or catheters, and rib/intercostal blocks. Although rib blocks may be accomplished via a variety of techniques, the two most common intra-operative techniques are video-assisted thoracoscopic surgery (VATS) intercostal nerve blocks and indwelling, subscapular catheters In general, neuraxial modalities such as thoracic epidural and para-vertebral injections/catheters are subject to a wide array of limitations, including patient coagulopathy (International Normalized Ratio > 1.5), co-existing spine fractures, peri-insertion, peri-removal withholding of venous thromboembolism pharmacoprophylaxis, and provider availability. For these reasons, our current practice is to insert a subscapular "pain catheter" at the conclusion of the SSRF operation; this catheter is able to deliver a continuous infusion of 0.25% bupivacaine and may be left in place for several days.
Although favorable results using the pain catheter have been published in patients with rib fractures who have not undergone SSRF, we have noticed several limitations to this treatment modality. First, position is highly variable; and, because the catheter is not truly in the space of the intercostal nerves, drug delivery is likely irregular. This variability may be particularly relevant in obese patients; and the median body mass index of patient who underwent SSRF at Denver Health is 29 kg/m\^2. Beyond catheter placement, we have also experienced issues with leakage of drug from the skin entry site of the catheter. Moreover, catheters frequently become dislodged or inadvertently removed during patient transport. Further, the indwelling foreign body likely introduces some risk of infection. Finally, the presence of the catheter is distressing to many patients.
Liposomal bupivacaine (Exparel, Pacira Pharmaceuticals, Inc., Parsippany, NJ, www.pacira.com) has been shown to provide sustained analgesia for up to 72 hours following a single injection of the drug delivery system. The safety and efficacy of liposomal bupivacaine has been evaluated in over 1,300 subjects and 21 clinical trials. Although many of these trials have included thoracic surgery patients, no trial has evaluated the efficacy and safety of liposomal bupivacaine administered to patients with rib fractures undergoing SSRF. Potential benefits as compared to current practice include directed injection immediately adjacent to the intercostal nerve using a VATS approach, as well as obviation of the need for an indwelling catheter. The hypothesis of the current clinical trial is that, among patients undergoing SSRF, liposomal bupivacaine delivered via video assisted thoracic surgery (VATS) is an intercostal nerve block that provides comparable analgesia to the pain catheter, as measured by pulmonary function, numeric pain scoring, and postoperative narcotic use.
126 studies on the registry are indexed under Rib Fractures; 28 are open to participants now.
This study's enrollment of 36 is below the median of 60 across 92 interventional studies indexed under Rib Fractures.
Browse Rib Fractures studies →Denver Health and Hospital Authority is the lead sponsor of 84 studies on the registry; 4 are open to participants now.
Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bupivacaine indwelling OnQ pain pump catheter will be placed in the subscapular space at the time of surgery, at infusion of 12 ml/hr of 0.25% bupivacaine, and left in place for a maximum of 120 hours
Drug: Bupivacaine indwelling catheter
A single injection of liposomal bupivacaine: mixture of 20 mL liposomal bupivacaine, 20 mL 0.25% bupivacaine, and 10 mL sterile saline (50 mL total), will be delivered in the intercostal space during VATS (with a 178 mm, 22 gauge needle, at ribs 3-8).
Drug: Liposomal bupivacaine injection
A single injection of liposomal bupivacaine is administered at the time of SSRF, directly to the fracture site via VATS
Also known as: Exparel
Bupivacaine indwelling OnQ pain pump catheter is placed in the subscapular space at the time of SSRF for continuous bupivacaine infusion post op
Also known as: OnQ pain pump, Continuous infusion of bupivacaine
Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score
The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry \< 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.
Time frame: Median SCARF scores were recorded for the first 5 postoperative days.
Daily Narcotic Requirements Using Equi-analgesic Doses
Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.
Time frame: Mean narcotic requirement scores were recorded for the first 5 postoperative hospital inpatient days.
Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA)
The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.
Time frame: 72 hours
Participants were recruited based on physician referral for surgical stabilization of rib fracture (SSRF) at Denver Health from November 2017 through July 2020.
| Milestone | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection |
|---|---|---|
| Started | 18 | 18 |
| Completed | 16 | 18 |
| Not completed | 2 | 0 |
| Withdrew: Orif cancelled due to patient's cognitive decline, withdrawn from study at this time | 2 | 0 |
The SCARF score is a validated, dynamic tool that ranges from 0-4, with 0 being the best score and 4 being the worst. One point is given for each of the following four parameters: (1) respiratory rate ≥ 20 breaths per minute; (2) numeric pain score ≥ 5; (3) incentive spirometry \< 50% of predicted based upon a nomogram including sex, height, and age; (4) cough deemed inadequate to clear respiratory secretions by respiratory therapists. The parameters used to calculate the SCARF score are summed to create the total 0-4 score and these results were recorded by clinical personnel not involved in the trial. SCARF scores were taken at 10 am daily for all postoperative inpatient hospital days, however due to variance in length of stay, only scores from the first 5 postoperative days were recorded for the purpose of this results analysis. Scores were then aggregated across the patients and timeframe to result in one median score per group.
| score on a scale | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection |
|---|---|---|
| Daily Sequential Clinical Assessment of Respiratory Function (SCARF) Score | 2 (0 to 4) | 2 (0 to 4) |
Narcotic pain medication requirements were recorded daily over the duration of inpatient hospital stay, however due to variance in length of stay, only the first 5 postoperative days were recorded for this analysis. Scores were averaged across patients providing one daily postoperative mean score per treatment group. The narcotics provided to patients varied based on standard of care, so an Equi-Analgesic Scale was used to standardize dosages across narcotic type. A 1:1 ratio for narcotic dosages is calculated with the following measured as equivalent: 1.5 milligrams (mg) of intravenous (IV) Hydromorphone; 7.5 mg of per oral (PO) Hydromorphone; 100 micrograms (mcg) of IV Fentanyl; 10 mg of IV Morphine; 30 mg of PO Morphine; 20 mg of PO Oxycodone (Percocet); and 30 mg of PO Hydrocodone (Vicodin). In the context of this scale, lower scores are best, indicating fewer narcotics required and higher scores are worse indicating the need for more narcotics based on subjective patient pain.
| units on a scale | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection |
|---|---|---|
| Postoperative Day #1 | 8.8 ± 13 | 6.5 ± 8.5 |
| Postoperative Day #2 | 6.8 ± 10.1 | 4.0 ± 6.9 |
| Postoperative Day #3 | 4.0 ± 6.1 | 2.6 ± 3.3 |
| Postoperative Day #4 | 4.2 ± 5.7 | 1.6 ± 1.5 |
| Postoperative Day #5 | 4.1 ± 7.4 | 2.2 ± 2.3 |
The failure of LRA for this study was defined as the percentage number of instances a patient required a secondary LRA modality within 72 hours of placement of the primary modality for either treatment arm. Requirement of this secondary LRA was determined by the patients' medical team with criteria based on subjective patient experience of pain.
| percentage of participants | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection |
|---|---|---|
| Percentage of Participants Experiencing Failure of Primary Loco-Regional Analgesia (LRA) | 18.8 | 5.6 |
Collected over Adverse event data were collected throughout the participants' stay in the hospital or for 28 days, whichever length of time was the shorter duration.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Bupivacaine Indwelling Catheter | 0/16 (0%) | 0/16 (0%) | 3/16 (18.8%) |
| Liposomal Bupivacaine Injection | 0/18 (0%) | 0/18 (0%) | 1/18 (5.6%) |
| Event | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection |
|---|---|---|
| Hospital ReadmissionSocial circumstances | 1/16 | 0/18 |
| OR TakebackSkin and subcutaneous tissue disorders | 1/16 | 0/18 |
| ED VisitSocial circumstances | 1/16 | 0/18 |
| Hospital ReadmissionInjury, poisoning and procedural complications | 0/16 | 1/18 |
The baseline analysis did not include two patients who were withdrawn from the study.
| Age, Categorical(Participants) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 11 | 15 | 26 |
| >=65 years | 5 | 3 | 8 |
| Age, Continuous(years) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Mean | 53.3 (18 to 81) | 52.3 (37 to 85) | 52.8 (18 to 85) |
| Sex: Female, Male(Participants) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Female | 5 | 8 | 13 |
| Male | 11 | 10 | 21 |
| Ethnicity (NIH/OMB)(Participants) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Hispanic or Latino | 6 | 5 | 11 |
| Not Hispanic or Latino | 10 | 13 | 23 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 16 | 16 | 32 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Body Mass Index (BMI)(kg/m^2) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Mean | 26 (20.4 to 34.8) | 27.2 (16.45 to 36.8) | 26.6 (16.45 to 36.8) |
| Injury Severity Score (ISS)(units on a scale) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Mean | 19.5 (9 to 38) | 22.1 (9 to 38) | 20.8 (9 to 38) |
| Number of Participants with Asthma(Participants) | Bupivacaine Indwelling Catheter | Liposomal Bupivacaine Injection | Total |
|---|---|---|---|
| Count of participants | 2 | 3 | 5 |
3 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
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Studies of the drug tested here: Liposomal Bupivacaine
Denver Health and Hospital Authority