Traumatic Rib Fracture(s)Phase 4NCT04198662
Rib Fracture Analgesia Using Cryoanalgesia
A Phase 4 study testing Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas) and Intercostal nerve block ropivacaine with epinephrine in people with Traumatic Rib Fracture(s), run by University of California, San Diego at 1 site in United States.
Trial summary
Rib fractures are one of the most common injuries in trauma patients. These fractures are associated with significant pain as well as decreased ability to inspire deeply or cough to clear secretions, which together lead to pulmonary complications and a high degree of morbidity and mortality. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Traumatic Rib Fracture(s)
- What is being tested?
- Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas) and Intercostal nerve block ropivacaine with epinephrine
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2020to 27 Aug 2024
- Phase
- Phase 4
- 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
- Adult patients of at least 18 years of age
- having a total of 1-6 rib fractures at least 3 cm distal to the costo-transverse joint sustained within the previous 3 days (bilateral fractures are acceptable, but the total of the two sides combined must not exceed 6 fractures)
- regional anesthetic requested by the admitting service
- accepting of a cryoneurolysis procedure
Who cannot join
- chronic opioid use (daily use within the 2 weeks prior to surgery and duration of use > 4 weeks
- pregnancy
- incarceration
- inability to communicate with the investigators
- morbid obesity (body mass index > 40 kg/m2)
- possessing any contraindication specific to cryoneurolysis such as a localized infection at the treatment site, cryoglobulinemia, cold urticaria and Reynaud's Syndrome
Show all 13Show fewer
- any patient unable to correctly perform incentive spirometry as this is the primary outcome measure
- any patient with any degree of decreased mental capacity as determined by the surgical service
- any reason an investigator believes study participation would not be in the best interest of the potential subject
- flail chest
- chest tube
- fracture of the 1st rib on either side
- any moderate or severe pain (NRS>3) unrelated to the rib fracture(s), as best determined by the patient and investigator
Trial locations and contacts
1 site in 1 country.
United States1 site
University California San Diego
San Diego, California, 92103
About this study
Official title: Intercostal Cryoneurolysis Following Traumatic Rib Fractures
Rib fractures are one of the most common injuries in trauma patients. These fractures are associated with significant pain as well as decreased ability to inspire deeply or cough to clear secretions, which together lead to pulmonary complications and a high degree of morbidity and mortality. Peripheral nerve blocks as well as epidural blocks have been used with success to improve pain control in rib fracture patients and have been associated with decreased pulmonary complications and improved outcomes. However, a single-injection nerve block lasts less than 24 hours; and, even a continuous nerve block is generally limited to 3-4 days. The pain from rib fractures usually persists for multiple weeks or months. In contrast to local anesthetic-induced nerve blocks, a prolonged block lasting a few weeks/months may be provided by freezing the nerve using a process called "cryoneurolysis". The goal of this multicenter, randomized, double-masked, sham-controlled, parallel-arm study is to evaluate the potential of cryoanalgesia to decrease pain and improve pulmonary mechanics in patients with rib fractures.
Read the detailed description
The ultimate objective of the proposed line of research is to determine if cryoanalgesia is an effective treatment for pain associated with rib fractures; and, if this analgesic modality improves pulmonary mechanics measured with incentive spirometry.
Specific Aim 1: To determine if, compared with current and customary analgesia for rib fracture(s), intercostal nerve cryoneurolysis improves maximum inspiratory volume.
Hypothesis 1a: The maximum inspired volume will be significantly increased on the day following the procedure [primary endpoint] as well as at other time points following the procedure [secondary end points] with intercostal cryoanalgesia as compared single-injection local anesthetic-based intercostal nerve blocks [measured with an incentive spirometer].
Hypothesis 1b: The maximum inspired volume as a percentage of the baseline will be significantly increased on the day following the procedure [secondary endpoint of greatest interest], as well as at other time points following the procedure [secondary end points] with intercostal cryoanalgesia as compared with single-injection local anesthetic-based intercostal nerve blocks [measured with an incentive spirometer].
Specific Aim 2: To determine if, compared with current and customary analgesia, intercostal nerve cryoneurolysis decreases the pain associated with rib fracture(s).
Hypothesis 2a: The severity of rib fracture pain at rest will be significantly decreased within the 12 months following the procedure with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2b: The severity of rib fracture pain when using the spirometer or coughing will be significantly decreased within the 12 months following the procedure with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2c: The incidence of chronic pain will be significantly decreased 6 and 12 months following a rib fracture with intercostal cryoeurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2d: The severity of chronic pain will be significantly decreased 6 and 12 months following a rib fracture with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Study Overview Day 0 Baseline pain levels and spirometry Subjects randomized and cryoneurolysis/sham procedure administered Post-block pain levels and spirometry repeated
Days 1, 2, 7 Pain levels, opioid consumption, sleep disturbances due to pain, and incentive spirometry values collected [as well as the day of discharge]
Months 0.5, 1, 1.5 , 2, 3, 6, and 12 Pain levels, opioid consumption, sleep disturbances due to pain, and pain interference collected [and incentive spirometry if subject has spirometer available]
Subjects will be individuals who present to one of the UCSD hospitals with rib fracture(s) and significant pain. All will be following the same protocol and the subjects from all institutions will be combined for the analysis.
Treatment group assignment (randomization). Subjects will be allocated to one of two possible treatments stratified by unilateral vs. bilateral fractures:
- active cryoneurolysis (sham local anesthetic intercostal blocks)
- sham cryoneurolysis (active local anesthetic intercostal blocks)
Computer-generated randomization lists created by the UC San Diego Investigational Drug Service will be used to create sealed, opaque randomization envelopes with the treatment group assignment enclosed in each envelope labeled with the randomization number. The lists will be kept by the Investigational Drug Service and not provided to the investigators until completion of data collection (1 year following enrollment of the final subject).
The specific intercostal nerves targeted will depend on the injury site. The treatment sites will be cleansed with chlorhexidine gluconate and isopropyl alcohol. Using the optimal ultrasound transducer for the specific anatomic location and subject anatomy (linear vs curvilinear array), the target nerves will be identified in a transverse cross-sectional (short axis) view. The intercostal nerve of each fractured rib as well as the level above and below will be treated with the protocol below:
Intercostal nerve block procedure: The target nerve will be visualized with ultrasound. Local anesthetic (1% lidocaine) will be used to infiltrate the skin and underlying muscle at each entry point. A 20 g Tuohy needle will be introduced through the skin wheel and along the anesthetized muscle tract. For subjects randomized to active cryo, 3 mL of normal saline will be injected into the muscle superficial to the nerve; and for subjects randomized to sham cryo, 3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block.
Cryoneurolysis procedure: Cryoneurolysis probes are available for a console neurolysis device (PainBlocker, Epimed, Farmers Branch, Texas) that either (1) pass nitrous oxide to the tip inducing freezing temperatures; or, (2) vent the nitrous oxide at the base of the probe so that no gas reaches the probe tip, resulting in no temperature change. The latter is a sham procedure since without the temperature change, no ice ball forms and therefore the target nerve is not affected. An angiocatheter/introducer will be inserted beneath the ultrasound transducer and directed until the probe tip is immediately adjacent to the target nerve. The angiocatheter needle will be removed, leaving the angiocatheter through which the appropriate Epimed probe will be inserted until it is adjacent to the target nerve. The cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation (active or sham) separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. For the sham probes, the nitrous oxide will be vented prior to reaching the probe shaft, resulting in a lack of perineural temperature change.
The process will be repeated with the same treatment probe for any additional nerves (e.g., all nerves will receive either active cryoneurolysis or sham/placebo, and not a mix of the two possible treatments).
Statistical Analysis: The primary endpoint is the maximum inspired volume measured by incentive spirometry the day following treatment. There is no accepted minimal clinically-relevant change in incentive spirometry volume. However, the median (IQR) of inspired volume for patients with rib fracture(s) is 1250 (750-1750) mL; and, ISV<1000 mL is associated with an increased risk of acute respiratory failure. The investigators will therefore use the difference between 1250 and 1000 (250 mL) as the minimal clinically-relevant difference. However, there is high variability in the reported increase in inspired volume with various regional analgesic interventions such as continuous intercostal nerve blocks and serratus plane blocks, and the investigators will therefore increase our enrollment to account for an unpredicted increase in variability or non-normal data distribution.
But, assuming a normal distribution, the interquartile range is approximately 1.35 standard deviations (SDs). Therefore an interquartile range of 250-50 = 200 mL (Hernandez et al. 2019) corresponds to, approximately, an SD of 200/1.35 = 148 mL. Assuming this SD of 148 mL, a sample size of n=7 per group provides 80% power to detect a group difference of d=250 mL per group with two sided Type 1 Error 5%. To allow for a larger-than-anticipated SD, we will enroll 10 subjects per group with an evaluable primary outcome measure (n=20 for both groups combined). Accounting for drop-outs, we request a maximum enrollment of 30 subjects.
Continuous data will be summarized with mean, SDs, medians, quartiles, and ranges; and displayed with box-and-whisker plots by group and in aggregate. Key baseline characteristics will be tested between groups using two-sample t-tests, and summarized with Cohen's D, for continuous measures; and Fisher's Exact test for categorical variables. The primary outcome is maximum incentive spirometry volume (ISV) measured in mL on POD 1. The group difference will be tested using Welch's two-sample test. Secondary outcomes will also be tested with the two-sample t-test. No multiplicity adjustments will be applied for these secondary outcomes. The Wilcoxon signed-rank test will be used as a sensitivity analysis. Secondary analyses will include a Mixed Model of Repeated Measures with fixed-effects for time, time-by-group, unilateral vs bilateral, and the number of fractures. The model will treat time as a categorical variable and will assume a compound symmetric correlation and heterogeneous variance with respect to time. The estimated mean difference between groups at the final scheduled timepoint will be the parameter of interest and will be tested using Kenward-Roger degrees of freedom. Outcomes only measured at baseline and a single follow-up timepoint will be analyses with Analysis of Covariance (ANCOVA). The dependent variable will be change from baseline, and covariates will include group, baseline outcome, unilateral vs bilateral, and the number of fractures. Missing data is not expected due to the short follow-up in this study. However, if missing data issues arise, the investigators will use multiple imputation which is robust to covariate-dependent Missing at Random, and tipping point analyses under various Missing Not at Random assumptions.
The Investigational Drug Pharmacists and investigators doing the study procedures will be the only individuals aware of the treatment group assignments. The Investigational Drug Service will not provide the treatment group assignments to the investigators until the completion of data collection for all subjects; and will only provide "Treatment A" vs "Treatment B" assignments for the initial statistical analysis. Only at the completion of statistical analysis will each treatment be revealed to the investigators.
- Conditions
- Traumatic Rib Fracture(s)
- Being tested
- Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas), Intercostal nerve block ropivacaine with epinephrine, Sham cryoneurolysis with a Painblocker, Placebo intercostal nerve block with normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas)Device
The cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis.
Intercostal nerve block ropivacaine with epinephrineDrug
3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block(s)
Sham cryoneurolysis with a PainblockerDevice
The cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. For the sham probes, the nitrous oxide will be vented prior to reaching the probe shaft, resulting in a lack of perineural temperature change.
Placebo intercostal nerve block with normal salineDrug
3 mL of normal saline will be injected perineurally to provide placebo intercostal nerve blocks
| Study group | Role | What they receive |
|---|---|---|
| Cryoneurolysis and placebo intercostal nerve block | Active comparator | Active cryoneurolysis: 3 mL of normal SALINE will be injected into the muscle superficial to the nerve followed by an ACTIVE cryoneurolysis procedure using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. Receives: Device: Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas); Drug: Placebo intercostal nerve block with normal saline |
| Sham cryoneurolysis and active intercostal nerve block | Sham comparator | Sham cryoneurolysis: 3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block followed by a SHAM cryoneurolysis procedure with a probe that vents the nitrous oxide prior to reaching the probe tip using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. Receives: Drug: Intercostal nerve block ropivacaine with epinephrine; Device: Sham cryoneurolysis with a Painblocker |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Inspired Volume
maximum inspired volume measured on a handheld incentive spirometer based on the American Association of Respiratory Care (AARC) clinical practice guideline.[Restrepo. Respirated Care 2011] The best of three measurements will be recorded as the maximum inspired volume.
Measured: Day 1 of study treatment
Secondary outcomes (8)
Maximum Inspired Volume
maximum inspired volume measured on a handheld incentive spirometer based on the American Association of Respiratory Care (AARC) clinical practice guideline.[Restrepo. Respirated Care 2011] The best of three measurements will be recorded as the maximum inspired volume.
Measured: Days 0, 1, 2, 7, 14, and Months 1, 1.5, and 2
Spirometry Pain
Worst pain level during the same-day spirometry use as measured using the 11-point Numeric Rating Scale with 0= no pain and 10= worst imaginable pain.
Measured: Days 0, 1, 2, 7, 14, and Months 1, 1.5, and 2
Brief Pain Inventory (Pain Scale)
The Brief Pain Inventory (Pain Scale) measures pain intensities: (1) worst pain; (2) least pain; (3) average pain; and (4) current pain. Each of these is measured using a 0-10 numeric rating scale, in which 0 is equivalent to no pain and 10 the worst imaginable. Then, all 4 are added together to produce a scale with values ranging from 0-40, with 0 equivalent to no pain and 40 the maximum pain.
Measured: Days 1, 2, and 7
Brief Pain Inventory (Interference Scale)
The Brief Pain Inventory (Interference Scale) assesses pain's interference with physical and emotional functioning (time frame: previous 24 h). The instrument measures interference with physical and emotional functioning using a 0-10 scale (0 = no interference; 10 = complete interference). The seven interference questions involve general activity, mood, walking ability, normal work activities (both inside and outside of the home), relationships, sleep, and enjoyment of life. These seven responses are then combined to produce an interference scale (0-70), with 0 equivalent to no interference (good) and 70 equivalent to the maximum interference (bad).
Measured: Day 14, and Months 1, 1.5, 2, 3, 6, and 12
Sleep Disturbances Due to Pain
Recorded as the number of awakenings subject-identified as due to pain during the previous evening
Measured: Days 1, 2, 7, 14; Months 1, 1.5, 2, 3, 6, and 12
Oral Opioid Consumption
Recorded as the amount of oral oxycodone-equivalent analgesics consumed in previous 24 hours (measured in mg)
Measured: Days 1, 2, 7, 14; Months 1, 1.5, 2, 3, 6, and 12
Intravenous Opioid Consumption
Recorded as the amount of intravenous morphine-equivalent analgesics consumed in previous 24 hours (measured in mg)
Measured: Days 1, 2, 7, 14
Day of Discharge
The number of days following the study procedure of primary discharge from the hospital
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Dec 2019
- Study start3 Apr 2020
- Primary completion28 Aug 2023
- Study completion27 Aug 2024
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.
- Other trials for Traumatic Rib Fracture(s)Studies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicenter, randomized, double-masked, sham-controlled, parallel design, clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian M. Ilfeld, MD, MS, University of California, San Diego
- Investigators
- Brian M Ilfeld, MD, MS, Principal investigator, University California San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04198662
- Sponsor's protocol ID
- Rib Fracture & Spirometry/Cryo
- Status last verified
- Oct 2024
- First submitted
- 4 Dec 2019
- Last updated
- 10 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intercostal Cryoneurolysis Following Traumatic Rib Fractures
- ClinicalTrials.gov ID
- NCT04198662
- Acronym / sponsor ID
- Rib Fracture & Spirometry/Cryo
- Conditions
- Traumatic Rib Fracture(s)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Study start
- 3 Apr 2020 (actual)
- Primary completion
- 28 Aug 2023 (actual)
- Study completion
- 27 Aug 2024 (actual)
- First posted
- 13 Dec 2019 (actual)
- Results
- Posted 10 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rib fractures are one of the most common injuries in trauma patients. These fractures are associated with significant pain as well as decreased ability to inspire deeply or cough to clear secretions, which together lead to pulmonary complications and a high degree of morbidity and mortality. Peripheral nerve blocks as well as epidural blocks have been used with success to improve pain control in rib fracture patients and have been associated with decreased pulmonary complications and improved outcomes. However, a single-injection nerve block lasts less than 24 hours; and, even a continuous nerve block is generally limited to 3-4 days. The pain from rib fractures usually persists for multiple weeks or months. In contrast to local anesthetic-induced nerve blocks, a prolonged block lasting a few weeks/months may be provided by freezing the nerve using a process called "cryoneurolysis". The goal of this multicenter, randomized, double-masked, sham-controlled, parallel-arm study is to evaluate the potential of cryoanalgesia to decrease pain and improve pulmonary mechanics in patients with rib fractures.
Detailed description
The ultimate objective of the proposed line of research is to determine if cryoanalgesia is an effective treatment for pain associated with rib fractures; and, if this analgesic modality improves pulmonary mechanics measured with incentive spirometry.
Specific Aim 1: To determine if, compared with current and customary analgesia for rib fracture(s), intercostal nerve cryoneurolysis improves maximum inspiratory volume.
Hypothesis 1a: The maximum inspired volume will be significantly increased on the day following the procedure [primary endpoint] as well as at other time points following the procedure [secondary end points] with intercostal cryoanalgesia as compared single-injection local anesthetic-based intercostal nerve blocks [measured with an incentive spirometer].
Hypothesis 1b: The maximum inspired volume as a percentage of the baseline will be significantly increased on the day following the procedure [secondary endpoint of greatest interest], as well as at other time points following the procedure [secondary end points] with intercostal cryoanalgesia as compared with single-injection local anesthetic-based intercostal nerve blocks [measured with an incentive spirometer].
Specific Aim 2: To determine if, compared with current and customary analgesia, intercostal nerve cryoneurolysis decreases the pain associated with rib fracture(s).
Hypothesis 2a: The severity of rib fracture pain at rest will be significantly decreased within the 12 months following the procedure with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2b: The severity of rib fracture pain when using the spirometer or coughing will be significantly decreased within the 12 months following the procedure with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2c: The incidence of chronic pain will be significantly decreased 6 and 12 months following a rib fracture with intercostal cryoeurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Hypothesis 2d: The severity of chronic pain will be significantly decreased 6 and 12 months following a rib fracture with intercostal cryoneurolysis as compared with subjects receiving single-injection local anesthetic-based intercostal nerve blocks [measured using the Numeric Rating Scale for pain].
Study Overview Day 0 Baseline pain levels and spirometry Subjects randomized and cryoneurolysis/sham procedure administered Post-block pain levels and spirometry repeated
Days 1, 2, 7 Pain levels, opioid consumption, sleep disturbances due to pain, and incentive spirometry values collected [as well as the day of discharge]
Months 0.5, 1, 1.5 , 2, 3, 6, and 12 Pain levels, opioid consumption, sleep disturbances due to pain, and pain interference collected [and incentive spirometry if subject has spirometer available]
Subjects will be individuals who present to one of the UCSD hospitals with rib fracture(s) and significant pain. All will be following the same protocol and the subjects from all institutions will be combined for the analysis.
Treatment group assignment (randomization). Subjects will be allocated to one of two possible treatments stratified by unilateral vs. bilateral fractures:
- active cryoneurolysis (sham local anesthetic intercostal blocks)
- sham cryoneurolysis (active local anesthetic intercostal blocks)
Computer-generated randomization lists created by the UC San Diego Investigational Drug Service will be used to create sealed, opaque randomization envelopes with the treatment group assignment enclosed in each envelope labeled with the randomization number. The lists will be kept by the Investigational Drug Service and not provided to the investigators until completion of data collection (1 year following enrollment of the final subject).
The specific intercostal nerves targeted will depend on the injury site. The treatment sites will be cleansed with chlorhexidine gluconate and isopropyl alcohol. Using the optimal ultrasound transducer for the specific anatomic location and subject anatomy (linear vs curvilinear array), the target nerves will be identified in a transverse cross-sectional (short axis) view. The intercostal nerve of each fractured rib as well as the level above and below will be treated with the protocol below:
Intercostal nerve block procedure: The target nerve will be visualized with ultrasound. Local anesthetic (1% lidocaine) will be used to infiltrate the skin and underlying muscle at each entry point. A 20 g Tuohy needle will be introduced through the skin wheel and along the anesthetized muscle tract. For subjects randomized to active cryo, 3 mL of normal saline will be injected into the muscle superficial to the nerve; and for subjects randomized to sham cryo, 3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block.
Cryoneurolysis procedure: Cryoneurolysis probes are available for a console neurolysis device (PainBlocker, Epimed, Farmers Branch, Texas) that either (1) pass nitrous oxide to the tip inducing freezing temperatures; or, (2) vent the nitrous oxide at the base of the probe so that no gas reaches the probe tip, resulting in no temperature change. The latter is a sham procedure since without the temperature change, no ice ball forms and therefore the target nerve is not affected. An angiocatheter/introducer will be inserted beneath the ultrasound transducer and directed until the probe tip is immediately adjacent to the target nerve. The angiocatheter needle will be removed, leaving the angiocatheter through which the appropriate Epimed probe will be inserted until it is adjacent to the target nerve. The cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation (active or sham) separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. For the sham probes, the nitrous oxide will be vented prior to reaching the probe shaft, resulting in a lack of perineural temperature change.
The process will be repeated with the same treatment probe for any additional nerves (e.g., all nerves will receive either active cryoneurolysis or sham/placebo, and not a mix of the two possible treatments).
Statistical Analysis: The primary endpoint is the maximum inspired volume measured by incentive spirometry the day following treatment. There is no accepted minimal clinically-relevant change in incentive spirometry volume. However, the median (IQR) of inspired volume for patients with rib fracture(s) is 1250 (750-1750) mL; and, ISV<1000 mL is associated with an increased risk of acute respiratory failure. The investigators will therefore use the difference between 1250 and 1000 (250 mL) as the minimal clinically-relevant difference. However, there is high variability in the reported increase in inspired volume with various regional analgesic interventions such as continuous intercostal nerve blocks and serratus plane blocks, and the investigators will therefore increase our enrollment to account for an unpredicted increase in variability or non-normal data distribution.
But, assuming a normal distribution, the interquartile range is approximately 1.35 standard deviations (SDs). Therefore an interquartile range of 250-50 = 200 mL (Hernandez et al. 2019) corresponds to, approximately, an SD of 200/1.35 = 148 mL. Assuming this SD of 148 mL, a sample size of n=7 per group provides 80% power to detect a group difference of d=250 mL per group with two sided Type 1 Error 5%. To allow for a larger-than-anticipated SD, we will enroll 10 subjects per group with an evaluable primary outcome measure (n=20 for both groups combined). Accounting for drop-outs, we request a maximum enrollment of 30 subjects.
Continuous data will be summarized with mean, SDs, medians, quartiles, and ranges; and displayed with box-and-whisker plots by group and in aggregate. Key baseline characteristics will be tested between groups using two-sample t-tests, and summarized with Cohen's D, for continuous measures; and Fisher's Exact test for categorical variables. The primary outcome is maximum incentive spirometry volume (ISV) measured in mL on POD 1. The group difference will be tested using Welch's two-sample test. Secondary outcomes will also be tested with the two-sample t-test. No multiplicity adjustments will be applied for these secondary outcomes. The Wilcoxon signed-rank test will be used as a sensitivity analysis. Secondary analyses will include a Mixed Model of Repeated Measures with fixed-effects for time, time-by-group, unilateral vs bilateral, and the number of fractures. The model will treat time as a categorical variable and will assume a compound symmetric correlation and heterogeneous variance with respect to time. The estimated mean difference between groups at the final scheduled timepoint will be the parameter of interest and will be tested using Kenward-Roger degrees of freedom. Outcomes only measured at baseline and a single follow-up timepoint will be analyses with Analysis of Covariance (ANCOVA). The dependent variable will be change from baseline, and covariates will include group, baseline outcome, unilateral vs bilateral, and the number of fractures. Missing data is not expected due to the short follow-up in this study. However, if missing data issues arise, the investigators will use multiple imputation which is robust to covariate-dependent Missing at Random, and tipping point analyses under various Missing Not at Random assumptions.
The Investigational Drug Pharmacists and investigators doing the study procedures will be the only individuals aware of the treatment group assignments. The Investigational Drug Service will not provide the treatment group assignments to the investigators until the completion of data collection for all subjects; and will only provide "Treatment A" vs "Treatment B" assignments for the initial statistical analysis. Only at the completion of statistical analysis will each treatment be revealed to the investigators.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicenter, randomized, double-masked, sham-controlled, parallel design, clinical trial
| Arm | Type | Receives |
|---|---|---|
| Cryoneurolysis and placebo intercostal nerve block | Active comparator | Device: Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas), Drug: Placebo intercostal nerve block with normal salineActive cryoneurolysis: 3 mL of normal SALINE will be injected into the muscle superficial to the nerve followed by an ACTIVE cryoneurolysis procedure using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. |
| Sham cryoneurolysis and active intercostal nerve block | Sham comparator | Drug: Intercostal nerve block ropivacaine with epinephrine, Device: Sham cryoneurolysis with a PainblockerSham cryoneurolysis: 3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block followed by a SHAM cryoneurolysis procedure with a probe that vents the nitrous oxide prior to reaching the probe tip using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients of at least 18 years of age
- having a total of 1-6 rib fractures at least 3 cm distal to the costo-transverse joint sustained within the previous 3 days (bilateral fractures are acceptable, but the total of the two sides combined must not exceed 6 fractures)
- regional anesthetic requested by the admitting service
- accepting of a cryoneurolysis procedure
Key exclusion criteria (13 listed)
- chronic opioid use (daily use within the 2 weeks prior to surgery and duration of use > 4 weeks
- pregnancy
- incarceration
- inability to communicate with the investigators
- morbid obesity (body mass index > 40 kg/m2)
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 |
|---|---|---|
| Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas)The cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. For active probes, the nitrous oxide will be deployed to the tip where a drop in temperature to -70°C will result in cryoneurolysis. | Device | Cryoneurolysis and placebo intercostal nerve block |
| Intercostal nerve block ropivacaine with epinephrine3 mL of ropivacaine 0.5% (with epinephrine) will be injected perineurally to provide the intercostal nerve block(s) | Drug | Sham cryoneurolysis and active intercostal nerve block |
| Sham cryoneurolysis with a PainblockerThe cryoneurolysis device will be triggered using 2 cycles of 2-minute gas activation separated by 1-minute defrost periods. For the sham probes, the nitrous oxide will be vented prior to reaching the probe shaft, resulting in a lack of perineural temperature change. | Device | Sham cryoneurolysis and active intercostal nerve block |
| Placebo intercostal nerve block with normal saline3 mL of normal saline will be injected perineurally to provide placebo intercostal nerve blocks | Drug | Cryoneurolysis and placebo intercostal nerve block |
Primary outcome
Maximum Inspired Volume
Time frame: Day 1 of study treatment
maximum inspired volume measured on a handheld incentive spirometer based on the American Association of Respiratory Care (AARC) clinical practice guideline.[Restrepo. Respirated Care 2011] The best of three measurements will be recorded as the maximum inspired volume.
8 secondary outcomes
Maximum Inspired Volume
Time frame: Days 0, 1, 2, 7, 14, and Months 1, 1.5, and 2
Spirometry Pain
Time frame: Days 0, 1, 2, 7, 14, and Months 1, 1.5, and 2
Brief Pain Inventory (Pain Scale)
Time frame: Days 1, 2, and 7
Brief Pain Inventory (Interference Scale)
Time frame: Day 14, and Months 1, 1.5, 2, 3, 6, and 12
Sleep Disturbances Due to Pain
Time frame: Days 1, 2, 7, 14; Months 1, 1.5, 2, 3, 6, and 12
Oral Opioid Consumption
Time frame: Days 1, 2, 7, 14; Months 1, 1.5, 2, 3, 6, and 12
Intravenous Opioid Consumption
Time frame: Days 1, 2, 7, 14
Day of Discharge
Time frame: through study completion, an average of 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Traumatic Rib Fracture(s)
Recruiting
Erector Spinae Plane vs Serratus Anterior Plane Catheter Infusions for Acute Pain Management in Patients With Traumatic Rib Fractures
Traumatic Rib Fracture(s), Traumatic Rib Fracture
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.
Brian M Ilfeld, MD, MS principal investigator
University California San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Cryoneurolysis with a Painblocker (Epimed International, Farmers Branch, Texas) and Intercostal nerve block ropivacaine with epinephrine in people with Traumatic Rib Fracture(s), run by University of California, San Diego at 1 site 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 4 inclusion and 13 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 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 10 Oct 2024). 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?
Maximum Inspired Volume (time frame: Day 1 of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Oct 2024.