PERSIST: Trial of Extended Release Bupivacaine for Pain Relief After Surgery

• Sponsor: Durect (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02574520
• Collaborator: (none)
• Enrollment: 399
• Locations: 21
• Arms: 2
• Actual Duration (Months): 21
• Patients Per Site: 19
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This is a research study of SABER® -Bupivacaine, an experimental medication designed to reduce pain for up to 3 days after surgery. Given once by the surgeon at the end of surgery, SABER® - Bupivacaine delivers a locally-acting pain reliever directly to the surgical wound.

The purpose of this study is to measure how well it works in reducing pain after laparoscopic cholecystectomy (surgery to remove the gall bladder) and to investigate the safety of SABER®-Bupivacaine (its side effects).

Condition or Disease	Intervention/Treatment	Phase
Post Operative Pain	Drug: SABER-Bupivacaine (Part 1); Drug: SABER-Bupivacaine (Part 2); Drug: Saline Placebo; Drug: Bupivacaine HCl	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 399 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled (Part 1) or Active-controlled (Part 2) Trial of SABER® -Bupivacaine for the Management of Postoperative Pain Following Laparoscopic Cholecystectomy (PERSIST)
• Actual Study Start Date: Nov 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Aug 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Part 1 SABER-Bupivacaine and Saline Placebo	Drug: SABER-Bupivacaine (Part 1); 5 ml once at end of surgery; Other Names: POSIMIR® bupivacaine solution ; Drug: Saline Placebo; 5 ml once at end of surgery; Other Names: placebo
Active Comparator: Part 2 SABER-Bupivacaine and Bupivacaine HCl	Drug: SABER-Bupivacaine (Part 2); 5 ml once at end of surgery; Other Names: POSIMIR® bupivacaine solution ; Drug: Bupivacaine HCl; 0.5%, 15 ml, once at end of surgery

Outcome Measures

Primary Outcome Measures

1. Pain Intensity on Movement From 0-48 Hours Post-Treatment [Assessed from 0 to 48 hours post-dose, summary measure (see description) reported.]

   A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 13 planned time points from 0 to 48 hours post-treatment. The values reported are mean pain scores for each treatment group.

Secondary Outcome Measures

1. Pain Intensity Using the NPRS-11 With Movement [Assessed from 0 to 72 hours post-dose, summary measure (see description) reported.]

   A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 17 planned time points from 0 to 72 hours post-treatment. The values reported are mean pain scores for each treatment group.

2. Total IV Morphine-equivalent Dose of Rescue Opioids [0-72 hrs. post dose (after surgery)]

   IV morphine-equivalent dose

3. Composite Endpoint of Silverman's Integrated Analgesic (SIA) Assessment Score [0 to 72 hours]

   Score of Integrated Analgesia (SIA) is a composite endpoint that integrates pain assessment scores with opioid use over various collections of timepoints by ranking the pain score and the opioid use separately across treatments. After the scores are computed the means are calculated across time points to provide a single overall treatment effect. The composite SIA score ranges from -200 to 200 with -200 being the best case and 200 the worst case.

4. Subjects Not Taking Rescue Medication From PACU Discharge to 72 Hours [From PACU Discharge to 72 Hours post-treatment]

   Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl

5. Time to First Opioid Rescue Medication Use After Discharge From the PACU [From PACU Discharge to 72 Hours post-treatment]

   Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl

6. Time to PACU Discharge Eligibility as Assessed by Modified Post-Anesthesia Discharge Scoring System (mPADSS) [From admission to discharge from PACU (Approximately 0 to 12 hours)]

   mPADSS is a tool used to determine eligibility for discharge from the PACU after ambulatory surgery. It includes an assessment of parameters such as vital signs, activity level, nausea/vomiting, pain, and surgical bleeding. For this trial, evaluation of eligibility for PACU discharge by mPADSS has been slightly modified to provide a standardized means of assessing eligibility for PACU discharge across multiple investigative sites and also ensures that nonmedical complications, such as a missing ride home, do not interfere with evaluation of test drug effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients scheduled for elective outpatient laparoscopic cholecystectomy using a conventional 4-port laparoscopic procedure.

• Must be able and willing to provide written informed consent, complete trial-related procedures, and communicate with the trial staff.

• Males and females 18 years of age or older.

• ASA Class I, II, or III.

• Patients of child-bearing potential must agree to use a medically acceptable method of contraception to prevent pregnancy for the duration of their participation in the trial.

• Must be living close enough to the investigative site to attend the four scheduled follow-up clinic visits.

Exclusion Criteria:

• Pregnant or nursing females.

• Patients with absolute or relative contraindications to laparoscopic cholecystectomy.

• Patients with prior midline abdominal surgery who are at risk for adhesions that may complicate laparoscopic cholecystectomy and/or accurate pain assessments.

• Patients requiring emergency surgery or urgent surgery (fewer than 5 days between screening and surgery).

• Patients with a pre-planned overnight stay or pre-planned hospital admission.

• Patients scheduled for single incision, mini trocars, natural orifice transluminal endoscopic surgery (NOTES), robotic laparoscopic procedures, or any procedure (other than cholangiograms and minimal adhesiolysis) in addition to laparoscopic cholecystectomy.

• Patients with known hypersensitivity to amide local anesthetics such as bupivacaine.

• Patients with acute pain that is not due to cholecystitis.

• Patients with a history of chronic pain unrelated to gallbladder disease.

• Patients with ongoing depression or psychosis.

• Patients undergoing long-term treatment with opioids or other analgesics, including acetaminophen, NSAIDs, anticonvulsants (gabapentin or pregabalin), and antidepressants (SSRIs, SNRIs, and tricyclics), but not including daily low-dose aspirin.

• Patients who are being treated chronically with systemic corticosteroids or who will require peri-operative corticosteroids because of adrenal insufficiency (inhalational or topical corticosteroids are permitted).

• Patients who may be unsuitable for opioid administration (such as sensitivity [e.g., history of severe nausea and vomiting] hypersensitivity, known history of abuse or addiction, or unwillingness to take prescribed rescue opioids).

• Use of anticoagulants and antiplatelet drugs (with exception of low dose aspirin) in the 1 week prior to surgery.

• Patients who are incapable of operating the electronic diary.

• Patients participating in any other trial with an investigational drug or device concurrently or less than 30 days prior to surgery for this trial.

• Patients who, in the Investigator's opinion, should not participate in the trial or may not be capable of following the trial procedures for any reason.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Durect Study Site 04	Florence	Alabama	United States	35360
2	Durect Study Site 03	Sheffield	Alabama	United States	35660
3	DURECT Study Site 24	Arcadia	California	United States	91007
4	Durect Study Site 15	Fontana	California	United States	92335
5	Durect Study Site 02	Laguna Hills	California	United States	92653
6	Durect Study Site 18	Laguna Hills	California	United States	92653
7	Durect Study Site 22	Pensacola	Florida	United States	32503
8	Durect Study Site 12	Indianapolis	Indiana	United States	46202
9	Durect Study Site 21	Royal Oak	Michigan	United States	48073
10	Durect Study Site 17	Jackson	Mississippi	United States	39202
11	Durect Study Site 16	Las Vegas	Nevada	United States	89104
12	Durect Study Site 20	Las Vegas	Nevada	United States	89109
13	Durect Study Site 05	Stony Brook	New York	United States	11794
14	Durect Study Site 13	Durham	North Carolina	United States	27710
15	Durect Study Site 09	Cleveland	Ohio	United States	44106
16	Durect Study Site 11	Cleveland	Ohio	United States	44111
17	Durect Study Site 07	Cleveland	Ohio	United States	44195
18	Durect Study Site 14	Philadelphia	Pennsylvania	United States	19107
19	Durect Study Site 08	Houston	Texas	United States	77004
20	DURECT Study Site 01	Houston	Texas	United States	77043
21	Durect Study Site 23	Plano	Texas	United States	75093

Sponsors and Collaborators

• Durect

Investigators

• Study Director: Dave Ellis, MD, Durect

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 8, 2017

More Information

Publications

None provided.

• Responsible Party: Durect
• ClinicalTrials.gov Identifier: NCT02574520
• Other Study ID Numbers: C803-028
• First Posted: Oct 14, 2015
• Last Update Posted: Jul 13, 2021
• Last Verified: Jun 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Durect: Post-operative pain; non-opioid analgesic; opioid reduction; laparoscopic cholecystectomy; laparoscopic surgery; bupivacaine; extended release; locally acting analgesic
• Additional relevant MeSH terms: Pain, Postoperative; Bupivacaine; Pharmaceutical Solutions

Study Results

Participant Flow

Recruitment Details	The study was conducted at 22 sites in the US. First subject was randomized on 17 November 2015. Study completion date was on 16 Aug 2017.

Arm/Group Title	SABER-Bupivacaine (Part 1)	Saline Placebo (Part 1)	SABER-Bupivacaine (Part 2)	Bupivacaine HCL (Part 2)
Arm/Group Description	5 ml once at end of surgery	5 ml once at end of surgery	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Period Title: Overall Study
STARTED	48	46	153	152
Dosed	46	46	148	148
COMPLETED	46	46	148	144
NOT COMPLETED	2	0	5	8

Baseline Characteristics

Arm/Group Title	SABER-Bupivacaine (Part 1)	Saline Placebo (Part 1)	SABER-Bupivacaine (Part 2)	Bupivacaine HCL (Part 2)	Total
Arm/Group Description	5 ml once at end of surgery	5 ml once at end of surgery	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery	Total of all reporting groups
Overall Participants	48	46	153	152	399
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.0 (14.2)	41.8 (12.8)	45.5 (13.5)	44.7 (13.9)	44.8 (13.67)
Sex: Female, Male (Count of Participants)
Female	31 64.6%	29 63%	115 75.2%	117 77%	292 73.2%
Male	17 35.4%	17 37%	38 24.8%	35 23%	107 26.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	2 4.2%	2 4.3%	5 3.3%	6 3.9%	15 3.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	7 14.6%	4 8.7%	6 3.9%	9 5.9%	26 6.5%
White	39 81.3%	40 87%	141 92.2%	135 88.8%	355 89%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 0.7%	2 1.3%	3 0.8%
Region of Enrollment (participants) [Number]
United States	48 100%	46 100%	153 100%	152 100%	399 100%

Outcome Measures

1. Primary Outcome

Title	Pain Intensity on Movement From 0-48 Hours Post-Treatment
Description	A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 13 planned time points from 0 to 48 hours post-treatment. The values reported are mean pain scores for each treatment group.
Time Frame	Assessed from 0 to 48 hours post-dose, summary measure (see description) reported.

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 2) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified primary outcome measure that included the SABER-Bupivacaine (Part 1) arm or the Saline Placebo (Part 1) arm.

Arm/Group Title	Part 2/SABER-Bupivacaine	Part 2/Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	148	148
Mean (Standard Error) [score on a scale]	5.55 (0.065)	5.87 (0.059)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 2/SABER-Bupivacaine, Part 2/Bupivacaine HCl
	Comments	Pain Intensity on Movement 0-48 hr
	Type of Statistical Test	Superiority
	Comments	Primary
Statistical Test of Hypothesis	p-Value	0.124
	Comments
	Method	ANOVA
	Comments	Mixed model with repeated measures (MMRM) for scheduled pain measurements was estimated with time as a repeating factor within subject.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.84 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.24
	Estimation Comments	Least squares mean from the MMRM described in the Statistical Test of Hypothesis.

2. Secondary Outcome

Title	Pain Intensity Using the NPRS-11 With Movement
Description	A derived measure computed based on a patient-reported numerical pain rating scale assessing pain as a whole number from 0 (no pain) to 10 (worst pain imaginable) when the subject sits up from a supine position. This measure was evaluated by electronic diary at 17 planned time points from 0 to 72 hours post-treatment. The values reported are mean pain scores for each treatment group.
Time Frame	Assessed from 0 to 72 hours post-dose, summary measure (see description) reported.

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Mean (Standard Error) [score on a scale]	4.94 (0.049)	5.40 (0.052)

3. Secondary Outcome

Title	Total IV Morphine-equivalent Dose of Rescue Opioids
Description	IV morphine-equivalent dose
Time Frame	0-72 hrs. post dose (after surgery)

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Mean (Standard Error) [IV morphine equivalent (mg)]	21.4 (1.37)	22.6 (1.58)

4. Secondary Outcome

Title	Composite Endpoint of Silverman's Integrated Analgesic (SIA) Assessment Score
Description	Score of Integrated Analgesia (SIA) is a composite endpoint that integrates pain assessment scores with opioid use over various collections of timepoints by ranking the pain score and the opioid use separately across treatments. After the scores are computed the means are calculated across time points to provide a single overall treatment effect. The composite SIA score ranges from -200 to 200 with -200 being the best case and 200 the worst case.
Time Frame	0 to 72 hours

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Mean (Standard Error) [score on a scale]	-17.3 (8.83)	-1.5 (9.33)

5. Secondary Outcome

Title	Subjects Not Taking Rescue Medication From PACU Discharge to 72 Hours
Description	Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl
Time Frame	From PACU Discharge to 72 Hours post-treatment

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Number [participants]	57 118.8%	42 91.3%

6. Secondary Outcome

Title	Time to First Opioid Rescue Medication Use After Discharge From the PACU
Description	Pooled SABER-Bupivacaine parts 1 + 2 vs. Bupivacaine HCl
Time Frame	From PACU Discharge to 72 Hours post-treatment

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Median (95% Confidence Interval) [hours]	5.5	6.1

7. Secondary Outcome

Title	Time to PACU Discharge Eligibility as Assessed by Modified Post-Anesthesia Discharge Scoring System (mPADSS)
Description	mPADSS is a tool used to determine eligibility for discharge from the PACU after ambulatory surgery. It includes an assessment of parameters such as vital signs, activity level, nausea/vomiting, pain, and surgical bleeding. For this trial, evaluation of eligibility for PACU discharge by mPADSS has been slightly modified to provide a standardized means of assessing eligibility for PACU discharge across multiple investigative sites and also ensures that nonmedical complications, such as a missing ride home, do not interfere with evaluation of test drug effects.
Time Frame	From admission to discharge from PACU (Approximately 0 to 12 hours)

Outcome Measure Data

Analysis Population Description

mITT Population, results for only the prespecified analysis population {SABER-Bupivacaine (Part 1 and Part 2 combined) and Bupivacaine HCl (Part 2)} are provided, there was no prespecified secondary outcome measure that included the Saline Placebo (Part 1) arm or the SABER-Bupivacaine (Part 1) arm as a standalone treatment group.

Arm/Group Title	Part 1 and Part 2: SABER-Bupivacaine	Part 2: Bupivacaine HCl
Arm/Group Description	5 ml once at end of surgery	0.5%, 15 ml, once at end of surgery
Measure Participants	194	148
Median (95% Confidence Interval) [hours]	1.8	1.9

Adverse Events

Time Frame	Approximately 0-60 days after surgery (duration of time over which each participant was assessed).
Adverse Event Reporting Description	Systematic and Non-systematic reported TEAEs of >5% (Safety Population)
Arm/Group Title	SABER-Bupivacaine (Part 1)		Saline Placebo (Part 1)		SABER-Bupivacaine (Part 2)		Bupivacaine HCL (Part 2)
Arm/Group Description	5 ml once at end of surgery		5 ml once at end of surgery		5 ml once at end of surgery		0.5%, 15 ml, once at end of surgery
All Cause Mortality
	SABER-Bupivacaine (Part 1)		Saline Placebo (Part 1)		SABER-Bupivacaine (Part 2)		Bupivacaine HCL (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/47 (0%)		0/148 (0%)		0/148 (0%)
Serious Adverse Events
	SABER-Bupivacaine (Part 1)		Saline Placebo (Part 1)		SABER-Bupivacaine (Part 2)		Bupivacaine HCL (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/45 (2.2%)		0/47 (0%)		5/148 (3.4%)		3/148 (2%)
Gastrointestinal disorders
Gastritis	0/45 (0%)		0/47 (0%)		0/148 (0%)		1/148 (0.7%)
Pancreatitis	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Pancreatitis acute	0/45 (0%)		0/47 (0%)		0/148 (0%)		1/148 (0.7%)
Hepatobiliary disorders
Bile duct stone	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Infections and infestations
Abdominal abscess	0/45 (0%)		0/47 (0%)		0/148 (0%)		1/148 (0.7%)
Injury, poisoning and procedural complications
Post procedural bile leak	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Investigations
Hepatic enzyme increased	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Metabolism and nutrition disorders
Dehydration	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Nervous system disorders
Dizziness	1/45 (2.2%)		0/47 (0%)		0/148 (0%)		0/148 (0%)
Vascular disorders
Hypotension	0/45 (0%)		0/47 (0%)		1/148 (0.7%)		0/148 (0%)
Other (Not Including Serious) Adverse Events
	SABER-Bupivacaine (Part 1)		Saline Placebo (Part 1)		SABER-Bupivacaine (Part 2)		Bupivacaine HCL (Part 2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/45 (95.6%)		47/47 (100%)		148/148 (100%)		146/148 (98.6%)
Gastrointestinal disorders
Constipation (Solicited)	20/45 (44.4%)		19/47 (40.4%)		65/148 (43.9%)		58/148 (39.2%)
Constipation	2/45 (4.4%)		2/47 (4.3%)		18/148 (12.2%)		13/148 (8.8%)
Diarrhoea	2/45 (4.4%)		3/47 (6.4%)		11/148 (7.4%)		7/148 (4.7%)
Dysgeusia (Solicited)	4/45 (8.9%)		2/47 (4.3%)		31/148 (20.9%)		24/148 (16.2%)
Vomiting (Solicited)	7/45 (15.6%)		7/47 (14.9%)		10/148 (6.8%)		17/148 (11.5%)
vomiting	2/45 (4.4%)		2/47 (4.3%)		16/148 (10.8%)		16/148 (10.8%)
Injury, poisoning and procedural complications
Incision site haemorrhage	3/45 (6.7%)		0/47 (0%)		10/148 (6.8%)		6/148 (4.1%)
Incision site pain	0/45 (0%)		2/47 (4.3%)		5/148 (3.4%)		8/148 (5.4%)
Post procedural contusion	41/45 (91.1%)		33/47 (70.2%)		142/148 (95.9%)		110/148 (74.3%)
Post procedural discharge	1/45 (2.2%)		1/47 (2.1%)		8/148 (5.4%)		6/148 (4.1%)
Procedural pain	19/45 (42.2%)		21/47 (44.7%)		32/148 (21.6%)		35/148 (23.6%)
Musculoskeletal and connective tissue disorders
Back pain	3/45 (6.7%)		3/47 (6.4%)		5/148 (3.4%)		11/148 (7.4%)
Nervous system disorders
Dizziness	1/45 (2.2%)		2/47 (4.3%)		13/148 (8.8%)		14/148 (9.5%)
Dizziness (Solicited)	11/45 (24.4%)		9/47 (19.1%)		38/148 (25.7%)		40/148 (27%)
Dysgeusia	1/45 (2.2%)		0/47 (0%)		13/148 (8.8%)		9/148 (6.1%)
Headache	1/45 (2.2%)		4/47 (8.5%)		16/148 (10.8%)		13/148 (8.8%)
Headache (Solicited)	17/45 (37.8%)		15/47 (31.9%)		53/148 (35.8%)		49/148 (33.1%)
Hypoaesthesia (Solicited)	0/45 (0%)		0/47 (0%)		8/148 (5.4%)		9/148 (6.1%)
Nausea	8/45 (17.8%)		11/47 (23.4%)		47/148 (31.8%)		51/148 (34.5%)
Nausea (solicited)	10/45 (22.2%)		15/47 (31.9%)		42/148 (28.4%)		45/148 (30.4%)
Paraesthesia (Solicited)	2/45 (4.4%)		2/47 (4.3%)		20/148 (13.5%)		21/148 (14.2%)
Somnolence (Solicited)	24/45 (53.3%)		22/47 (46.8%)		73/148 (49.3%)		65/148 (43.9%)
Somnolence	1/45 (2.2%)		0/47 (0%)		16/148 (10.8%)		12/148 (8.1%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/45 (11.1%)		2/47 (4.3%)		5/148 (3.4%)		2/148 (1.4%)
Skin and subcutaneous tissue disorders
Pruritus (Solicited)	5/45 (11.1%)		11/47 (23.4%)		31/148 (20.9%)		27/148 (18.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.