Post-operative Pain
Conditions
Keywords
Pulsed Radiofrequency Energy (PRFE), Pain, Postsurgical, Opioids, Pain relief, Medical device, Endorphins
Brief summary
Multicenter, randomized, controlled, double-blind study to evaluate the use of 3 days of pulsed radiofrequency energy (PRFE) to treat pain after bunionectomy surgery.
Detailed description
The clinical study's primary objective is to compare the overall analgesic effect of the Provant Therapy System (test device) to an identical sham device (placebo) in subjects experiencing post-operative pain following first metatarsal bunion surgery. The study hypothesis is that, over the first 72 hours (3 days) after the initial test device treatment, subjects treated with an active test device will show a statistically significant difference (reduction) in pain intensity scores when compared with subjects treated with a sham (placebo) device. Treatment with the test device will continue through the 168 hour (7 day) timepoint. Safety will be followed through 28 days.
Interventions
DEVICEPulsed Radiofrequency Energy (PRFE)
The intervention is pulsed radiofrequencyenergy (PRFE).
DEVICENo Pulsed Radiofrequency Energy (PRFE)
Sham (placebo) with no therapeutic device activity
Sponsors
Regenesis Biomedical, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Pre-operative Inclusion Criteria: * Adults aged 18-75 years old * Subject is scheduled to undergo primary, unilateral first metatarsal bunionectomy (no collateral procedures) under regional/local anesthesia and sedation * Subject meets the criteria for American Society of Anesthesiologists (ASA) Physical Status I or II. * Subject is willing to be confined at the investigative site for approximately 4 days including the day of surgery. * Subject is able to communicate meaningfully in English in order to complete study assessments and comply with all trial procedures. * Willingness to give written informed consent and to comply with all parts of the study protocol. * Female Subjects of child bearing potential are eligible only if they are not pregnant (negative pregnancy test at screening and before surgery), not lactating, and not planning to become pregnant during the study. * Female Subjects must be post-menopausal, surgically sterile, abstinent, or practicing, or agree to practice, an effective method of birth control if they are sexually active for the duration of the study (effective methods of birth control include prescription hormonal contraceptives, intrauterine devices, double-barrier methods, and/or male partner sterilization). Pre-Operative
Exclusion criteria
* Subject is scheduled to undergo Base wedge osteotomy, and/or Long-Z Hart bunionectomy procedure or any other procedure that does not conform to the surgical protocol. * Subject has received any investigational drug within 1 month prior to the Screening Visit or is enrolled in another clinical trial. * Subject has a history of drug abuse within 5 years of the screening visit, including a history of opioid (narcotic) analgesic abuse. * Subject has a history of any clinically significant cardiac, respiratory (except mild asthma), renal, hepatic, gastrointestinal, hematologic, endocrine or psychiatric disease or disorder, or any uncontrolled medical illness that in the investigator's judgment places the Subject at unacceptable risk for surgery or receipt of investigational therapy. * Subject has an ongoing, uncontrolled painful condition that in the opinion of the Investigator might have a confounding influence on the safety or efficacy analysis for this study. * Subject has received systemic corticosteroid administration within 1 month prior to surgery or is scheduled to receive systemic corticosteroid therapy at any time during the course of the study. * Subject is unwilling to abstain from alcohol from at least midnight the night before surgery through completion of all In-patient Treatment Period procedures and discharge from the investigative site. * Subject is unwilling to refrain from smoking during his/her stay at the investigative site. * Subject is currently receiving treatment, or has received treatment within the last two weeks, with antipsychotic drugs, monoamine oxidase inhibitors, duloxetine, gabapentin, carbamazepine, phenytoin, pregabalin or is receiving treatment with antidepressants that are not on a stable dose (the same dose for \>1 month). * Subject has a history of malignancy within the past five years with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin and/or localized carcinoma in situ of the cervix. * Subject has current evidence of alcohol abuse (regularly drinks more than four units of alcohol per day; 1 unit = ½ pint of beer, 1 glass of wine, or 1 ounce of spirit). * Infection (acute or chronic) involving the first metatarsal (or history of such infection) or any other disease of the foot/ankle that in the opinion of the investigator, places the Subject at increased risk for surgical complications or receipt of the investigational therapy. * Implanted pacemaker, defibrillator, neurostimulator, bone stimulator, cochlear implant, or other implanted device with metal lead(s). * Implanted metal in the index foot including planned intra-operative use of metallic screw or fixation device. * History of malignancy in the treatment area. * Subjects who are taking any dosage strength of daily opioids for more than 30 consecutive days, within the past three months prior to surgery. * Subject with fibromyalgia, complex regional pain syndrome or other chronic pain syndromes. * Subjects with neuropathic or sensory abnormalities of the lower extremities. Abnormal vibratory sensation and/or Semmes-Weinstein monofilament tests. * Subject with BMI \> 38. * Subject with known hypersensitivity, intolerance or contraindication to acetaminophen, oxycodone, morphine or any agent used in the anesthetic protocol that in the opinion of the Investigator will put the Subject at increased risk. Post-Operative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Analgesic Efficacy (Via SPID 0-72 Hrs) | Treatment with the test device twice per day, over 3 days (7 total treatments) | Sum of time-weighted Pain Intensity Differences (SPID). Pain relief was assessed at completion of first treatment, 45min,60min,90min,2hrs,3hrs,4hrs,6hrs following T0 and every 2hrs between 6AM to 10PM. After 10 PM and before 6AM, pain relief assessments were done every 4hrs. Subjects rated pain relief relative to baseline using a categorical scale: 0=none; 1=a little; 2=some; 3= a lot; 4 = complete. SPIDt = ∑PID x (time(t) - time(t-1)) x PID(i). A more negative SPID value means less pain. Total score of SPID ranged from a min value of -1091550.00 in the active arm and -2120130.00 in the sham arm and a max value of 603060.00 in the active arm and 1077630.00 in the sham arm. No absolute min and max scores were calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TOTPAR-Pain Relief Experienced by Patients T0-72 Hours | Treatment with the test device twice per day, over 3 days (7 total treatments) | Pain relief was assessed at completion of first study device treatment, 45 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours following T0 (±5 mins). Thereafter, pain relief was assessed every 2 hours (±5 mins) between 6AM to 10PM throughout the in-patient treatment period. After 10 PM and before 6AM, pain relief assessments were done every 4 hours. Subjects rated pain relief relative to baseline pain intensity using a categorical scale: 0=none; 1=a little; 2=some; 3= a lot; 4 = complete. Based on these scores, a time weighted pain relief score was calculated, Total Pain Relief (TOTPAR). TOTPAR-Pain Relief = ∑PID x (time(t) - time(t-1)) x PID(i). |
| Opioid Consumption Measured in Morphine Equivalents T0-72 Hours | Treatment with the test device twice per day, over 3 days (7 total treatments) | The total quantity of Supplemental Opioid analgesic administered throughout the study was recorded for each Subject. Opioid consumption prior to (T0) was not considered when calculating opioid consumption endpoints. |
| Number of Participants Who Assessed Pain Control at 72 Hours as Good, Very Good, or Excellent | After 3 days of treatment (T0-72 hours) | Number of participants who assessed pain control at 72 hours as good, very good, or excellent. |
| Time to First Use of Supplemental Analgesic Medication | Treatment with the test device twice per day, over 3 days (7 total treatments) | The time to first supplemental analgesic use was recorded. This was defined as the time from the initiation of the first study device treatment session (T0) to the time of administration of the first dose of post-T0 supplemental medication. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Study Device With PRFE This study arm receives pulsed radiofrequency energy (PRFE) from an active test device.
Pulsed Radiofrequency Energy (PRFE): The intervention is pulsed radiofrequencyenergy (PRFE). | 71 |
| Sham Study Device With no PRFE This study arm receives no pulsed radiofrequency energy (PRFE) from a sham test device.
No Pulsed Radiofrequency Energy (PRFE): Sham (placebo) with no therapeutic device activity | 68 |
| Total | 139 |
Baseline characteristics
| Characteristic | Active Study Device With PRFE | Sham Study Device With no PRFE | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 68 Participants | 67 Participants | 135 Participants |
| Age, Continuous | 46.2 years STANDARD_DEVIATION 13.61 | 44.7 years STANDARD_DEVIATION 13.35 | 45 years STANDARD_DEVIATION 13.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 15 Participants | 37 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 53 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 32 Participants | 33 Participants | 65 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 28 Participants | 66 Participants |
| Region of Enrollment United States | 71 participants | 68 participants | 139 participants |
| Sex: Female, Male Female | 57 Participants | 55 Participants | 112 Participants |
| Sex: Female, Male Male | 14 Participants | 13 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 71 | 0 / 68 |
| serious Total, serious adverse events | 0 / 71 | 0 / 68 |
Outcome results
Primary
Overall Analgesic Efficacy (Via SPID 0-72 Hrs)
Sum of time-weighted Pain Intensity Differences (SPID). Pain relief was assessed at completion of first treatment, 45min,60min,90min,2hrs,3hrs,4hrs,6hrs following T0 and every 2hrs between 6AM to 10PM. After 10 PM and before 6AM, pain relief assessments were done every 4hrs. Subjects rated pain relief relative to baseline using a categorical scale: 0=none; 1=a little; 2=some; 3= a lot; 4 = complete. SPIDt = ∑PID x (time(t) - time(t-1)) x PID(i). A more negative SPID value means less pain. Total score of SPID ranged from a min value of -1091550.00 in the active arm and -2120130.00 in the sham arm and a max value of 603060.00 in the active arm and 1077630.00 in the sham arm. No absolute min and max scores were calculated.
Time frame: Treatment with the test device twice per day, over 3 days (7 total treatments)
Population: P=0.3529
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Study Device With PRFE | Overall Analgesic Efficacy (Via SPID 0-72 Hrs) | -244890.0 units on a scale |
| Sham Study Device With no PRFE | Overall Analgesic Efficacy (Via SPID 0-72 Hrs) | -258030.00 units on a scale |
p-value: 0.3529ANCOVA
Secondary
Number of Participants Who Assessed Pain Control at 72 Hours as Good, Very Good, or Excellent
Number of participants who assessed pain control at 72 hours as good, very good, or excellent.
Time frame: After 3 days of treatment (T0-72 hours)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Active Study Device With PRFE | Number of Participants Who Assessed Pain Control at 72 Hours as Good, Very Good, or Excellent | 48 Participants |
| Sham Study Device With no PRFE | Number of Participants Who Assessed Pain Control at 72 Hours as Good, Very Good, or Excellent | 57 Participants |
Comparison: P = 0.5009p-value: 0.5009ANOVA
Secondary
Opioid Consumption Measured in Morphine Equivalents T0-72 Hours
The total quantity of Supplemental Opioid analgesic administered throughout the study was recorded for each Subject. Opioid consumption prior to (T0) was not considered when calculating opioid consumption endpoints.
Time frame: Treatment with the test device twice per day, over 3 days (7 total treatments)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Study Device With PRFE | Opioid Consumption Measured in Morphine Equivalents T0-72 Hours | 23.30 Morphine Equivalents |
| Sham Study Device With no PRFE | Opioid Consumption Measured in Morphine Equivalents T0-72 Hours | 20.30 Morphine Equivalents |
Comparison: P=0.1467p-value: 0.1467ANOVA
Secondary
Time to First Use of Supplemental Analgesic Medication
The time to first supplemental analgesic use was recorded. This was defined as the time from the initiation of the first study device treatment session (T0) to the time of administration of the first dose of post-T0 supplemental medication.
Time frame: Treatment with the test device twice per day, over 3 days (7 total treatments)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Active Study Device With PRFE | Time to First Use of Supplemental Analgesic Medication | 89 Minutes |
| Sham Study Device With no PRFE | Time to First Use of Supplemental Analgesic Medication | 87 Minutes |
p-value: 0.9038ANOVA
Secondary
TOTPAR-Pain Relief Experienced by Patients T0-72 Hours
Pain relief was assessed at completion of first study device treatment, 45 minutes, 60 minutes, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours following T0 (±5 mins). Thereafter, pain relief was assessed every 2 hours (±5 mins) between 6AM to 10PM throughout the in-patient treatment period. After 10 PM and before 6AM, pain relief assessments were done every 4 hours. Subjects rated pain relief relative to baseline pain intensity using a categorical scale: 0=none; 1=a little; 2=some; 3= a lot; 4 = complete. Based on these scores, a time weighted pain relief score was calculated, Total Pain Relief (TOTPAR). TOTPAR-Pain Relief = ∑PID x (time(t) - time(t-1)) x PID(i).
Time frame: Treatment with the test device twice per day, over 3 days (7 total treatments)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Active Study Device With PRFE | TOTPAR-Pain Relief Experienced by Patients T0-72 Hours | 327974.79 units on a scale |
| Sham Study Device With no PRFE | TOTPAR-Pain Relief Experienced by Patients T0-72 Hours | 364873.24 units on a scale |
p-value: 0.2766ANCOVA