A Randomized, Subject-Masked, Active-Controlled, Parallel-Arm Clinical Trial Comparing Pecs-2 and Paravertebral Nerve Blocks
Phase: PHASE4
Conditions: Breast Surgery
Sponsor: University of California, San Diego

Official Title:  Pectoralis Block vs Paravertebral Nerve 
Blocks for Breast Surgery 
 
 
 
 
 
NCT:  04742309 
 
 
 
 
 
Document date:  February 24, 2021 
 

 
 
UCSD Human Research Protections Program 
New Biomedical Application 
RESEARCH PLAN 
Instructions for completing the Research Plan are available on the HRPP website. 
The headings on this set of instructions correspond to the headings of the Research Plan. 
General Instructions: Enter a response for all topic headings.  
Enter “Not Applicable” rather than leaving an item blank if the item does not apply to this project. 
Version date: 9/30/2013 
1. 
PROJECT TITLE 
A Randomized, Subject-Masked, Active-Controlled, Parallel-Arm Clinical Trial Comparing Pecs-
2 and Paravertebral Nerve Blocks 
 
 
2. 
PRINCIPAL INVESTIGATOR  
Brian M. Ilfeld, MD, MS 
 
3. 
FACILITIES 
UCSD hospitals (JMC, Hillcrest, KOP) 
 
4. 
ESTIMATED DURATION OF THE STUDY 
Four years (1 month preparation, 36 months enrollment, 11 months publication prior to closure) 
 
5. 
LAY LANGUAGE SUMMARY OR SYNOPSIS (no more than one paragraph) 
Following painful surgical procedures of the breast, postoperative analgesia is often provided with a 
nerve block called a “paravertebral” block.  For intense, but shorter-duration acute pain, a single-
injection of numbing medicine is used which lasts about 12 hours.  Recently, a new type of block has 
been reported:  the “Pecs-2” block.  The theoretical benefits include ease of administration since it is 
closer to the skin (less deep) compared with the paravertebral block and therefore easier to identify 
and target with ultrasound (therefore increasing success rate); and, a lower risk of complications.  
Lastly, it might be easier to insert a tiny tube which would allow additional numbing medicine to be 
injected.   There are, therefore, multiple theoretical reasons to prefer the Pecs-2 over the 
paravertebral nerve block.  Unfortunately, it remains unknown if the pain control provided by this new 
type of block is comparable to that provided with the older block.  We therefore propose to compare 
these two blocks with a clinical study. 
 
6. 
SPECIFIC AIMS 
The overall objective of the proposed research is to determine the relative risks and benefits of Pecs-
2 versus paravertebral blocks for single-injection local anesthetic administration. 
 
Hypothesis 1:  Following breast surgery, analgesia will be non-inferior in the recovery room with a 
Pecs-2 block compared with a paravertebral block as measured with the Numeric Rating Scale. 
 
Hypothesis 2:  For breast surgery, opioid consumption will be non-inferior in the operating and 
recovery rooms with a Pecs-2 block compared with a paravertebral block (primary: cumulative 
intravenous morphine equivalents). 
 
Primary end point:  In order to claim that Pecs-2 blocks are non-inferior to paravertebral blocks, both 
Hypotheses 1 and 2 must be at least non-inferior. 
 
 
7. 
BACKGROUND AND SIGNIFICANCE 
Following painful surgical procedures of the breast, postoperative analgesia is often provided with a 
paravertebral nerve block (PVB).  For intense, but shorter-duration acute pain, a single-injection of 
local anesthetic is used with a duration of approximately 12 hours.  The PVB has several limitations:  
it can decrease blood pressure, and very rare—but serious—complications have occurred, including 

 
 
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neuraxial injection, neuraxial hematoma, and pleural puncture.1  An alternative block has been 
described:  the Pecs-2 block.2  The theoretical benefits include ease of administration since it is a 
plane superficial to the PVB and therefore easier to identify and target with ultrasound (therefore 
increasing success rate); and an increased safety margin:  there are few anatomic structures in the 
immediate area which could be injured with the needle.3  To date, 7 randomized trials involving Pecs-
2 block have been published, all involving mastectomy and a placebo control, and concluded that the 
Pecs-2 block does, in fact, provide post-mastectomy analgesia compared with a placebo control.4  
Six of 7 studies reported no related adverse events.  In one trial the occurrence of a hematoma 
and/or bleeding in three patients (2%) was reported, but it was unclear if these were related to the 
nerve block or a surgical complication. Of note, our proposed study includes subjects having breast 
surgery other than mastectomy, which has not been previously investigated (and also uses an active 
control—the paravertebral block—compared with placebo controls).  Lastly, the plane may be easier 
to catheterize for continuous peripheral nerve blocks relative to the relatively-small volume PVB.5 
 
There are therefore multiple theoretical reasons to prefer the Pecs-2 block.  Unfortunately, it remains 
unknown if the analgesia provided by this new technique is comparable to that provided with the 
PVB.1  We therefore propose to compare these two techniques with a randomized, subject-masked, 
active-controlled, parallel-arm, human subjects clinical trial. 
 
8. 
PROGRESS REPORT 
There are no preliminary or pilot study data. 
 
9. 
RESEARCH DESIGN AND METHODS 
This investigation will be a randomized, subject-masked, active-controlled parallel-arm, human 
subjects clinical trial.  Of note, we will be using standard-of-care local anesthetic under an FDA-
approved purpose and do not plan to research a possible change of indication or use of these 
medications as part of this research project.  The treatments in both groups are currently used at our 
institution and there is true clinical equipoise at this time.  The only difference in treatment between 
subjects who enroll versus those not enrolled in this study will be those who enroll will have the 
decision between which anatomic block location determined randomly, as opposed to the physician 
simply choosing him/herself. 
 
Enrollment.  Consenting adults undergoing breast surgery with a planned single-injection regional 
analgesic will be offered enrollment.  Patients undergoing breast surgery with a planned perineural 
catheter regional analgesic will be excluded.  Study inclusion will be proposed to eligible patients 
prior to surgery.  If a patient desires study participation, written, informed consent will be obtained 
using a current UCSD IRB-approved ICF.  Selection for inclusion will not be based on gender, race, 
or socioeconomic status.  The study population of interest includes men and women of all races and 
socioeconomic status.  Inclusion and exclusion criteria are listed in section #9 below. 
 
Preoperative Procedures.  Following written, informed consent, we will collect baseline 
anthropomorphic information (e.g., age, sex, height, and weight).  All subjects will have a peripheral 
intravenous (IV) catheter inserted, standard noninvasive monitors applied, supplemental oxygen 
administered via a nasal cannula or face mask, and placed in the sitting position.  Midazolam and 
fentanyl (IV) will be titrated for patient comfort, while ensuring that patients remain responsive to 
verbal cues.  Both possible block locations will be viewed with ultrasound.  If one or both of the 
locations is unacceptable for block placement in the clinician’s opinion, the subject will not be 

 
 
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randomized and will not proceed further with the study. 
 
Subjects will then be randomized using a computer-generated list and opaque, sealed envelopes to 
one of two treatment groups: (blocks of 4, stratified for unilateral vs. bilateral surgery): (1) Pecs-2 or 
(2) paravertebral block.  All blocks will be placed by a regional anesthesia fellow or resident under the 
direct supervision and guidance of a regional anesthesia attending (or by the attending themselves). 
 
For paravertebral blocks, a total of 18 mL of ropivacaine 0.5% with epinephrine will be administered 
per side (90 mg).  An equivalent mass of ropivacaine will be administered for the Pecs-2 blocks (90 
mg), but since more volume is required (30 mL per treated side), the concentration will be decreased 
to 0.3% ropivacaine (with epinephrine).  Therefore, for bilateral procedures, 90 mg will be 
administered bilaterally.  The area of needle insertion will be cleaned with chlorhexidine gluconate 
and isopropyl alcohol.  All blocks will be placed using standard UCSD ultrasound-guided techniques 
as previously described.3 
 
For Pecs-2 blocks and as described by Bashandy and Abbas,3 the needle will be advanced to the 
tissue plane between the pectoralis major and minor muscles at the vicinity of the pectoral branch of 
the acromiothoracic artery where 10 mL of local anesthetic will be deposited (Figs. 1-4).  In a similar 
manner, 20 mL will be deposited at the level of the third rib above the serratus anterior muscle with 
the intent of spreading injectate to the axilla. 
 
For paravertebral blocks, ropivacaine 0.5% 9 mL will be administered at each of two levels per side:  
the T3 and T5 levels for sides without axillary involvement; and at the T2 and T4 level for sides with 
axillary involvement. 
 
 
 
 
 
 
 

 
 
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Single-injection blocks will be considered successful if, within 30 minutes, the subject experiences 
decreased sensation to cold temperature with an alcohol pad over the approximate level of the 
ipsilateral 4th thoracic dermatome.  Misplaced blocks will be replaced successfully, or the patient 
excluded from further study participation.  For subjects undergoing bilateral surgical procedures, a 
block using the same protocol will be administered on the contralateral side. 
 
Intraoperatively, all subjects will receive a general anesthetic using inhaled and intravenous 
anesthetic and oxygen.  Intravenous fentanyl will be administered for cardiovascular responsiveness 
to noxious stimuli at the discretion of the anesthesia provider. 
 
Postop:  Subjects will be discharged with a prescription for oxycodone 5 mg tablets for 
supplementary analgesia and instructed to record the time at which they take their first opioid tablet 
as well as the time at which they believe the block starts to wear off. 
 
Outcome measurements (end points).  Pain scores will be recorded using the NRS.  Within the 
recovery room, pain scores, opioid requirements, and antiemetic administration will be recorded by 
nursing staff masked to treatment group.  The morning following surgery, all subjects will be 
contacted by phone or in person [if hospitalized] to record lowest, average, highest, and current pain 
scores; sleep disturbances, and nausea using a 0-10 Likert scale (0 = no nausea; 10 = vomiting).  
For outpatients, opioid requirements will be recorded while inpatients will have opioid requirements 
extracted from the electronic medical record.  In addition, we will extract antiemetic use from the 
electronic record.  We will collect the times at which subjects felt their block resolve and they 
consumed their first opioid analgesic pills following recovery room discharge. 
 
Hypothesis 1:  Following breast surgery, analgesia will be non-inferior in the recovery room with a 
Pecs-2 block compared with a paravertebral block as measured with the Numeric Rating Scale. 
 
Hypothesis 2:  For breast surgery, opioid consumption will be non-inferior in the operating and 
recovery rooms with a Pecs-2 block compared with a paravertebral block (primary: cumulative 
intravenous morphine equivalents). 
 
Primary end point:  In order to claim that Pecs-2 blocks are non-inferior to paravertebral blocks, both 
Hypotheses 1 and 2 must be at least non-inferior. 
 
 
Statistical methods.  Descriptive statistics will be provided by arm and in aggregate. Baseline 
characteristics of arms will be compared using the Wilcoxon-Mann-Whitney and Fisher’s Exact tests. 
Key characteristics that are significantly different (p<0.05) will be included as covariates in the 
analysis models. 
 
Primary aim.  We will test the noninferiority of the serratus nerve block compared to the 
paravertebral nerve block.  The 95% confidence interval (CI) associated with the Wilcoxon-Mann-
Whitney test will be derived for the group difference (paravertebral minus serratus) in median pain 
scores within the recovery room. If the lower limit of the 95% CI is greater than -1.25, we will 
conclude noninferiority.  If there are significant differences between the groups in any key 
characteristics, these characteristics will be included as covariates in a linear model. The same 
noninferiority margin (-1.25) will be applied to the 95% CI for the covariate adjusted group difference 
in mean pain derived from the linear model. 

 
 
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The noninferiority of the serratus nerve block with regard to total opioid consumption within the 
operating and recovery rooms will be tested in the same manner as pain, i.e. comparing the limits of 
a 95% CI associated with the Wilcoxon-Mann-Whitney test to a predefined noninferiority margin (in 
this case 2 mg). Covariate adjusted linear models will again be applied in the event that key 
characteristics are significantly different between the groups. 
 
Sample size justification.    Power for the Wilcoxon-Mann-Whitney derived noninferiority testing is 
based on 10,000 simulated trials. We simulated pain scores from a discrete distribution with median 
(interquartile range) 3 (2-5).6  Between the quartiles, the probability of each score was assumed 
constant.  The distribution for each group was assumed to be the same.  The sample size of n=50 
per group provides 82% power to detect noninferiority in pain with a margin of 1.25.  Similarly, opioid 
consumption was assumed to follow a truncated normal distribution with mean 2.5 mg and standard 
deviation 2 mg, and minimum value 0 mg.  The sample size of n = 50 per group provides at least 
95% power to detect noninferiority with margin 2 mg.  However, to account for any unanticipated 
increase in variability, we will enroll 25 additional subjects in each treatment group.  Therefore, we 
will enroll 75 subjects for each of the two treatments with primary end point values for a total 
enrollment of 150 subjects with a primary end point.  To allow for dropouts, we request a maximum 
enrollment of 175 subjects.  Noninferiority in pain is tested first, and if significant, noninferiority in 
opioid consumption is tested.  Under this hierarchical testing framework, no adjustment in alpha is 
necessary to control Type 1 error.7 
 
 
10. 
HUMAN SUBJECTS 
Inclusion criteria for the trial will be:  (1) undergoing unilateral or bilateral breast surgery with at 
least moderate postoperative pain anticipated; (2) analgesic plan includes a single-injection 
peripheral nerve block(s); and (3) age 18 years or older. 
 
Exclusion criteria for the trial will be:  (1) morbid obesity as defined by a body mass index > 40 
(BMI=weight in kg / [height in meters]2); (2) renal insufficiency (abnormal preoperative creatinine or 
eGFR ); (3) chronic opioid use (daily use within the 2 weeks prior to surgery and duration of use > 4 
weeks); (4) history of opioid abuse; (5) any comorbidity which results in moderate or severe 
functional limitation; (6) inability to communicate with the investigators or hospital staff; (7) 
pregnancy; (8) planned regional analgesic with perineural catheter placement; (9) incarceration; and 
(10) known allergy to amide local anestshetics.  We will recruit a maximum of 175 subjects.  
Selection for inclusion will not be based on race or socioeconomic status.  The study population of 
interest includes men and women of all races and socioeconomic status.  There will be no 
participants from vulnerable populations, such as pregnant women, children, or prisoners. 
 
11. 
RECRUITMENT AND PROCEDURES PREPARATORY TO RESEARCH 
Study inclusion will be proposed to eligible patients prior to surgery by the investigators.  Since the 
investigators will be contacting patients as part of their standard preoperative anesthesia 
consultation, HIPAA regulations will be adhered to.  For women of childbearing age with the 
possibility of pregnancy, a sample of urine is always collected for a pregnancy test prior to surgery—
regardless of study participation.  Pregnant patients will be excluded from study participation. 
 
12. 
INFORMED CONSENT 
If a patient desires study participation, written, informed consent will be obtained.  An investigator or 

 
 
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research assistant/coordinator (including regional anesthesia fellows) specifically trained in both 
study details and appropriate consenting procedures will attain verbal and written informed subject 
consent.  The method of documenting consent will be using written informed consent form (including 
a written HIPAA consent form and UCSD Experimental Subjects’ Bill of Rights).  Due to the fact that 
nearly all qualifying patients will be relatively healthy and all will be undergoing relatively minor 
ambulatory surgical procedures, the overwhelming majority will not be seen in preoperative clinic on 
a day prior to the day of surgery.  Therefore, the study will be proposed the day of surgery in the 
preoperative area of the outpatient center (KOP) after patients present for their procedure.  Patients 
will not be rushed into making a decision regarding the study, and this is possible since (a) patients 
are brought to the center with far more time than necessary to ensure no surgical delays and (b) this 
is a relatively simple, straight-forward study with no medical/health risks and therefore should not be 
a particular burden on prospective subjects.  There will be approximately 20-40 minutes available for 
counseling subjects about the study and obtaining written informed consent before administration of 
sedation in the preoperative area. 
 
Following informed consent and the signing of the UCSD IRB-approved ICF and HIPAA documents, 
these documents will be copied and the copy placed in the patient’s medical record.  The subject will 
be provide a copy along with the Subjects’ Bill of Rights. 
 
13. 
ALTERNATIVES TO STUDY PARTICIPATION 
If a patient declines enrollment, they will receive their perioperative analgesic with the choice of which 
anatomic location to use (Pecs-2 or paravertebral block) determined by the attending regional 
anesthesiologist instead of randomly per study protocol. 
 
14. 
POTENTIAL RISKS 
The risks for both block locations include bleeding, infection, damage to nerves, inadequate pain 
relief, and injection into nearby structures including blood vessels, near or into spinal canal, and the 
lining of the lung.  Currently, it remains unknown whether or not there are relatively higher risks with 
one anatomic location over the other.  Given the proximity to the paravertebral, neuraxial, and pleural 
spaces, the risks of Pecs-2 and paravertebral blocks are felt to be similar.  However, due to the 
increased distance between the Pecs-2 and the pleura and neuraxis, these risks are thought to be 
decreased with an improved safety margin.  Although this speculation is hypothetical as no large 
series of ultrasound-guided Pecs-2 blocks have been published, there is the possibility that a 
patient’s risk might be affected by study participation if the attending physician would have chosen 
one of the two possible blocks, while the randomization indicates the other be used.  There is, 
however, the risk of loss of confidentiality with study participation. 
 
15. RISK MANAGEMENT PROCEDURES AND ADEQUACY OF RESOURCES 
The procedural risks involved with PVB and Pecs-2 blocks will be managed according to the 
complication.  All blocks will be performed after placement of intravenous access with adequate 
monitoring including continuous pulse oximetry, EKG, and noninvasive blood pressure.  
Resuscitation equipment will be readily available.  Hypotension will be treated pharmacologically 
according to the degree of hypotension.  Inadvertent pleural puncture will be diagnosed with chest 
radiography and subsequent interventions (such as tube thoracostomy) will be guided by consultation 
with surgery depending on the severity of the pneumothorax.  Inadvertent intravascular injection will 
be managed according to the degree of cardiovascular compromise with intralipid readily available 
during all blocks.  Bleeding, neurologic, and infectious complications will be managed according to 
the degree of neurologic sequelae in consultation with surgery. Horner’s syndrome will be managed 

 
 
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expectantly as it recedes with the resolution of the block. 
 
The following study procedures will be done to maintain confidentiality of this study: hard copies will 
be kept in the locked medical offices of the investigators (KOP or the ACTRI) and the patients’ own 
medical charts.  Any digitized records will be stored in encrypted files on password-protected 
computers. 
 
16. PRIVACY AND CONFIDENTIALITY CONSIDERATIONS INCLUDING DATA ACCESS AND MANAGEMENT 
Following study participation, all hard copies of the ICF and single-page CRF will be kept in the 
locked offices of the investigators (KOP or the ACTRI).  Digitized records will be de-identified using 
subjects’ randomization numbers—only the single-page hardcopy CRF will contain identifiable 
personal health information as well as the randomization number.  As such, subject research records 
will only be identified by a study number. 
 
Prospective subjects will be approached in their own “cubical” in the preoperative area prior to 
surgery—these have curtains to provide privacy to patients waiting for surgery.  With the curtains 
closed, the study will be described to the patient who will be provided with an informed consent and 
HIPAA form to review, subsequently having all questions and concerns addressed. 
 
17. POTENTIAL BENEFITS 
There are no known immediate medical benefits to study participation for the individual.  However, 
future patients may benefit if we determine that one anatomic location provides greater relative 
benefits or fewer relative risks.  In addition, current subjects may themselves benefit if they require 
future surgery and a postoperative analgesic. 
 
18. RISK/BENEFIT RATIO 
There is no known direct benefit to the subjects. 
 
19. EXPENSE TO PARTICIPANT 
None.  
 
20. COMPENSATION FOR PARTICIPATION 
None. 
 
21. PRIVILEGES/CERTIFICATIONS/LICENSES AND RESEARCH TEAM RESPONSIBILITIES 
Principal Investigator, Brian M. Ilfeld, MD, MS, is a board-certified anesthesiologist with fellowship 
training in and 19 post-training years experience with regional anesthesia and perineural local 
anesthetic infusion.  Dr. Ilfeld holds a license to practice medicine in California.  Dr. Ilfeld has medical 
privileges at the UC Medical Centers.  Dr. Ilfeld, or another investigator, will follow all subjects.  Dr. 
Ilfeld will be responsible for the overall management of this study, as well as for the well-being of 
study subjects. 
 
Co-investigators, Jackie Sztain, MD, Rodney Gabriel, MD, MAS, Engy Said, MD, Bahareh 
Khatibi, MD, John Finneran, MD, Matthew Swisher, MD, MS, and Wendy Abramson, MD, are all 
board-certified anesthesiologists with fellowship training in ultrasound-guided regional anesthesia.  
All are skilled in both the anesthesia techniques and willing to proceed with either approach on a 
randomized basis.  In addition, Anne Wallace, MD, is a board-certified surgeon with decades 
experience involving breast surgery (and will not be administering any of the anesthetic blocks).  All 

 
 
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hold a license to practice medicine in California and have medical privileges at the UC Medical 
Centers.  All will help consent subjects, perform a history and physical exam, assist in placing nerve 
blocks (with the exception of Dr. Wallace) and collect outcome measurements. 
 
22. BIBLIOGRAPHY 
1. Naja Z, Longquvist PA. Somatic paravertebral nerve blockade. Incidence of failed block and 
complications. Anaesthesia 2001; 56: 1184-8 
2. Blanco R. The “pecs block”: A novel technique for providing analgesia after breast surgery.  
Anaesthesia; 66: 847-8 
3. Bashandy GMN and Abbas DN. Pectoral nerves I and II blocks in multimodal analgesia for 
breast cancer surgery:  A randomized clinical trial. Reg Anesth Pain Med 2015; 40: 68–74 
4. Lovett- 
5. Ilfeld BM, Madison SJ, Suresh PJ, Sandhu NS, Kormylo NJ, Malhotra N, Loland VJ, Wallace 
MS, Proudfoot JA, Morgan AC, Wen CH, Wallace AM.  Treatment of post-mastectomy pain 
with ambulatory continuous paravertebral nerve blocks: A randomized, triple-masked, placebo-
controlled study.  Reg Anesth Pain Med 2014; 39: 89-96  [UCSD IRB #100882] 
6. Kairaluoma PM, Bachmann MS, Korpinen AK., Rosenberg PH, Pere PJ. Single-injection 
paravertebral block before general anesthesia enhances analgesia after breast surgery with 
and without associated lymph node biopsy. Anesth Analg 2004; 99(6): 1837-43 
7. Mascha EJ, Turan A. Joint hypothesis testing and gatekeeping procedures for studies with 
multiple endpoints. Anesth Analg 2012; 114(6): 1304-17 
 
23. FUNDING SUPPORT FOR THIS STUDY 
This is a PI-initiated investigation.  Funding will be provided by the Department of Anesthesiology. 
 
24. BIOLOGICAL MATERIALS TRANSFER AGREEMENT 
Not applicable. 
 
 
25. INVESTIGATIONAL DRUG FACT SHEET AND IND/IDE HOLDER 
Not applicable. 
 
26. IMPACT ON STAFF 
The study will not impact nursing staff as subjects will be receiving a regional analgesic in one of the 
two anatomic locations regardless of study participation. 
 
27. CONFLICT OF INTEREST 
None. 
 
28. SUPPLEMENTAL INSTRUCTIONS FOR CANCER-RELATED STUDIES 
Not applicable. 
 
29. OTHER APPROVALS/REGULATED MATERIALS 
None. 
 
30. PROCEDURES FOR SURROGATE CONSENT AND/OR DECISIONAL CAPACITY ASSESSMENT 
Not applicable:  surrogate consent will not be accepted. 
 
 

 
 
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