Male Infertility
Conditions
Brief summary
The study is a drug trial comparing the post-operative pain control provided by liposomal bupivacaine (a local anesthetic) against standard bupivacaine (a different formulation of the local anesthetic) for men undergoing testicular sperm extraction.
Interventions
DRUGLiposomal Bupivacaine
After surgical sperm retrieval, the wound will be injected with liposomal bupivacaine (266 mg) mixed with standard bupivacaine (bupivacaine hydrochloride 50mg) for post-operative pain relief.
After surgical sperm retrieval, the wound will be injected only with standard bupivacaine (bupivacaine hydrochloride 100mg) for post-operative pain relief.
Sponsors
Pacira Pharmaceuticals, Inc
Weill Medical College of Cornell University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
The study model is a randomized double blind control trial.
Eligibility
Sex/Gender
MALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Men scheduled for surgical sperm retrieval for infertility * Men 18 years and older who can provide informed consent * No documented allergy to bupivacaine or celecoxib
Exclusion criteria
* Prior history of substance abuse * Any narcotic use within the last 3 months * Concomitant use of aspirin * Any of the following comorbidities: renal failure, heart disease, peptic ulcer disease, cerebrovascular disease, significant liver disease, untreated depression, chronic pain disorder, or bleeding diatheses * Medical history or concurrent illness that the investigator considers sufficiently serious to interfere with the conduct, completion, or results of this trial, or constitutes an unacceptable risk to the subject
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores 48 Hours After Surgery | First 48 hours after surgery | Every 8 hours in the first 48 hours post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 480 (maximum pain (score of 10) reported each time across 48 hours). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pain Scores 7 Days After Surgery | First 7 days after surgery | Every 12 hours in the first 7 days post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 1680 (maximum pain (score of 10) reported each time across 168 hours). |
| Narcotic Requirement | First 7 days after surgery | Total number of narcotic tablets required between the intervention and control arms during post-operative day 1 through 7. |
| Pain Scores 60 Hours After Surgery | First 60 hours after surgery | Every 12 hours in the first 60 hours post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 600 (maximum pain (score of 10) reported each time across 60 hours). |
| Pain Control Satisfaction | 7th day after surgery | Overall satisfaction of pain control regimen self reported on post-operative day 7. The prompt required a yes/no answer. The percent of participants answering yes will be compared between the two arms. |
| Percentage of Patients Not Requiring Any Narcotics | 7th day after surgery | The percentage of patients remaining opiate free by post-operative day 7. |
| Time to Narcotic Rescue | First 7 days after surgery | Time (in hours) to first rescue narcotic utilization between the two arms. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Liposomal Bupivacaine Participants in this arm will have a single injection of liposomal bupivacaine admixed with standard bupivacaine (266mg liposomal bupivacaine mixed with 50mg bupivacaine hydrochloride) at the conclusion of their surgical sperm retrieval procedure.
Liposomal Bupivacaine: After surgical sperm retrieval, the wound will be injected with liposomal bupivacaine (266 mg) mixed with standard bupivacaine (bupivacaine hydrochloride 50mg) for post-operative pain relief. | 25 |
| Standard Bupivacaine Participants in this arm will have a single injection of standard bupivacaine (100mg bupivacaine hydrochloride) at the conclusion of their surgical sperm retrieval procedure.
Standard Bupivacaine: After surgical sperm retrieval, the wound will be injected only with standard bupivacaine (bupivacaine hydrochloride 100mg) for post-operative pain relief. | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Liposomal Bupivacaine | Total | Standard Bupivacaine |
|---|---|---|---|
| Age, Continuous | 37.2 years STANDARD_DEVIATION 9.3 | 36.8 years STANDARD_DEVIATION 10.6 | 36.4 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 49 Participants | 25 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 | 2 Participants | 6 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 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 | 22 Participants | 41 Participants | 19 Participants |
| Region of Enrollment United States | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 25 Participants | 50 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 3 / 25 | 4 / 25 |
| serious Total, serious adverse events | 0 / 25 | 0 / 25 |
Outcome results
Primary
Pain Scores 48 Hours After Surgery
Every 8 hours in the first 48 hours post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 480 (maximum pain (score of 10) reported each time across 48 hours).
Time frame: First 48 hours after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Pain Scores 48 Hours After Surgery | 118.4 Scores*Hour | Standard Deviation 99.7 |
| Standard Bupivacaine | Pain Scores 48 Hours After Surgery | 98.2 Scores*Hour | Standard Deviation 68.9 |
p-value: 0.41t-test, 2 sided
Secondary
Narcotic Requirement
Total number of narcotic tablets required between the intervention and control arms during post-operative day 1 through 7.
Time frame: First 7 days after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Narcotic Requirement | 2.6 Count of narcotic tablets | Standard Deviation 4.4 |
| Standard Bupivacaine | Narcotic Requirement | 1.6 Count of narcotic tablets | Standard Deviation 3.1 |
p-value: 0.28Regression, Linear
Secondary
Pain Control Satisfaction
Overall satisfaction of pain control regimen self reported on post-operative day 7. The prompt required a yes/no answer. The percent of participants answering yes will be compared between the two arms.
Time frame: 7th day after surgery
Population: 3 subjects from the Liposomal Bupivacaine arm and 4 subjects from the Standard Bupivacaine arm weren't analyzed because they didn't provide answers to the yes/no prompt.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Liposomal Bupivacaine | Pain Control Satisfaction | Yes - Adequate pain control achieved | 22 Participants |
| Liposomal Bupivacaine | Pain Control Satisfaction | No - Adequate pain control not achieved | 0 Participants |
| Standard Bupivacaine | Pain Control Satisfaction | Yes - Adequate pain control achieved | 20 Participants |
| Standard Bupivacaine | Pain Control Satisfaction | No - Adequate pain control not achieved | 1 Participants |
p-value: 0.49Fisher Exact
Secondary
Pain Scores 60 Hours After Surgery
Every 12 hours in the first 60 hours post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 600 (maximum pain (score of 10) reported each time across 60 hours).
Time frame: First 60 hours after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Pain Scores 60 Hours After Surgery | 140.7 Scores*Hour | Standard Deviation 107.8 |
| Standard Bupivacaine | Pain Scores 60 Hours After Surgery | 116 Scores*Hour | Standard Deviation 83.2 |
p-value: 0.37t-test, 2 sided
Secondary
Pain Scores 7 Days After Surgery
Every 12 hours in the first 7 days post-surgery, subjects were prompted to report their pain score on the 11-point numerical pain rating scale, NRS-11 (Numerical Rating Scale, 11 points). 0 indicates no pain and 10 indicates worst possible pain. Each subject's pain scores were then plotted against time, and the area under the curve was then computed. The minimum composite score would be 0 (no pain ever reported), and the maximum composite score would be 1680 (maximum pain (score of 10) reported each time across 168 hours).
Time frame: First 7 days after surgery
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liposomal Bupivacaine | Pain Scores 7 Days After Surgery | 286.6 Scores*Hour | Standard Deviation 202.7 |
| Standard Bupivacaine | Pain Scores 7 Days After Surgery | 233.1 Scores*Hour | Standard Deviation 209.9 |
p-value: 0.36t-test, 2 sided
Secondary
Percentage of Patients Not Requiring Any Narcotics
The percentage of patients remaining opiate free by post-operative day 7.
Time frame: 7th day after surgery
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Liposomal Bupivacaine | Percentage of Patients Not Requiring Any Narcotics | No narcotics required | 15 Participants |
| Liposomal Bupivacaine | Percentage of Patients Not Requiring Any Narcotics | Narcotics required | 10 Participants |
| Standard Bupivacaine | Percentage of Patients Not Requiring Any Narcotics | No narcotics required | 16 Participants |
| Standard Bupivacaine | Percentage of Patients Not Requiring Any Narcotics | Narcotics required | 9 Participants |
p-value: 0.99Fisher Exact
Secondary
Time to Narcotic Rescue
Time (in hours) to first rescue narcotic utilization between the two arms.
Time frame: First 7 days after surgery
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Liposomal Bupivacaine | Time to Narcotic Rescue | 41 to 80 Hours After Surgery | 0 Participants |
| Liposomal Bupivacaine | Time to Narcotic Rescue | 121 to 160 Hours After Surgery | 2 Participants |
| Liposomal Bupivacaine | Time to Narcotic Rescue | 81 to 120 Hours After Surgery | 0 Participants |
| Liposomal Bupivacaine | Time to Narcotic Rescue | Never Required Narcotics | 13 Participants |
| Liposomal Bupivacaine | Time to Narcotic Rescue | 0 to 40 Hours After Surgery | 10 Participants |
| Standard Bupivacaine | Time to Narcotic Rescue | Never Required Narcotics | 13 Participants |
| Standard Bupivacaine | Time to Narcotic Rescue | 0 to 40 Hours After Surgery | 8 Participants |
| Standard Bupivacaine | Time to Narcotic Rescue | 41 to 80 Hours After Surgery | 0 Participants |
| Standard Bupivacaine | Time to Narcotic Rescue | 81 to 120 Hours After Surgery | 3 Participants |
| Standard Bupivacaine | Time to Narcotic Rescue | 121 to 160 Hours After Surgery | 1 Participants |
p-value: 0.78Log Rank