Clinical trial NCT03152929
Conditions: Breast Cancer
Keywords: Surgery Breast Pectoral Nerve Block Paravertebral Block Analgesia Mastectomy
Sponsor: Spectrum Health Hospitals
Start date: 2017-03-09; Completion date: 2019-05-21
Enrollment: 89 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare two standard methods of pain control management used at Spectrum Health for patients undergoing breast surgery. The two methods being compared are the paravertebral block (PVB) and the pectoral nerve block (PEC). Postoperative pain control is essential following any major operative procedure. A variety of methods have been used to ensure adequate pain control, each with its own advantages and risks. Increasingly, attention has focused on regional methods of analgesia, which may allow for reduction in systemic narcotic use and their associated complications. Proposed benefits of regional analgesia and a resultant reduction in narcotic use include decreased risk of cancer progression, decreased length of stay, and decreased risk of ileus.

Detailed description:
The purpose of this study is to compare the clinical profiles of two currently acceptable analgesia techniques. The most common regional block used to achieve postoperative analgesia following mastectomy is the paravertebral block, during which local anesthetic is injected into the paravertebral space which contains the thoracic spinal nerves, between the costotransverse ligament and the pleura. At our institution there has been recent interest in an alternative regional block. The pectoral nerve block is performed by injecting anesthetic between the pectoralis major and the pectoralis minor (PECs I) or between the pectoralis minor and the serratus anterior (PEC II).

The proposed advantage of the pectoral nerve block for regional anesthesia during breast surgery is equal analgesic efficacy with fewer potential complications.

Arms: arm 1: The Paravertebral Block is performed along the spine utilizing ultrasound guided technique (20-30 mL 0.5% Ropivacaine) arm 2: The Pectoral Nerve Block is performed anteriorly, at the level of the axillary line, also utilizing ultrasound guided technique (20-30 mL 0.5% Ropivacaine)
Interventions: intervention 1: Paravertebral Block intervention 2: Pectoral Nerve Block
Intervention descriptions: intervention 1: 20-30 mL 0.5% Ropivacaine intervention 2: 20-30 mL 0.5% Ropivacaine

Protocol documents:
Prot_SAP_000.pdf: 
 
Page 1 of 9 
1. Protocol Title: Paravertebral Block Versus Pectoral Nerve Block for Analgesia Following 
Mastectomy 
 
2. Investigator(s): Marianne Melnik MD, Paul Jaklitsch, MD, Melinda Miller, Leon Oostendorp, 
Jayne Paulson, Jennifer Carroll, MD, Matthew Dull, MD and Erica Burkheimer, MD 
 
3. Version Date:  March 30, 2018 
 
4. Objectives: 
I. 
Primary Objective:  To determine if pectoral nerve blocks (PECs) achieve equal 
analgesia following mastectomy, partial mastectomy or lumpectomy, with and without 
reconstruction, when compared to paravertebral blocks (PVBs). 
II. 
Secondary Objective:  To trend complication rates for PECs and PVBs. 
 
5. Background: 
Postoperative pain control is essential following any major operative procedure.  A variety of 
methods have been utilized to ensure adequate analgesia, each with its own advantages 
and risks.  Increasingly, attention has focused on regional methods of analgesia, which may 
allow for reduction in systemic narcotic use and their associated complications [1].  
Proposed benefits of regional analgesia and a resultant reduction in narcotic use include 
decreased risk of cancer progression, decreased length of stay, and decreased risk of ileus.   
 
The most common regional block used to achieve postoperative analgesia following 
mastectomy is the paravertebral block, during which local anesthetic is injected into the 
paravertebral space which contains the thoracic spinal nerves, between the costotransverse 
ligament and the pleura. At our institution there has been recent interest in an alternative 
regional block.  The pectoral nerve block is performed by injecting anesthetic between the 
pectoralis major and the pectoralis minor (PECs I) or between the pectoralis minor and the 
serratus anterior (PECs II) [2]. A serratus plane block is a modification of the PEC block, in 
which a local anesthetic is injected between the serratus anterior and latissimus dorsi 
muscles.   
 
The proposed advantage of the pectoral nerve block for regional anesthesia during breast 
surgery is equal analgesic efficacy with fewer potential complications.    
 
6. Setting of the Research: 
The study will take place at Spectrum Health Medical Center: Butterworth Hospital and 
Spectrum Health Blodgett Hospital with follow up through Spectrum Health Lemmen-Holton 
Cancer Pavilion and the Lake Drive locations.    
 
7. Resources Available to Conduct this Research: 
Surgeries will be performed by the Spectrum Health breast surgeons.  These surgeons 
perform approximately 300 mastectomies, partial mastectomies and lumpectomies per year.  
Even allowing for a percentage of patients who refuse participation, this should provide an 
adequate population base to recruit the required number of participants within 12 months.   
 
The regional anesthesia will be performed by the Anesthesia Medical Consultants’ on-call 
pain physician.  Subjects will be enrolled by Spectrum Health clinical research staff.   


 
Page 2 of 9 
Dr. Marianne Melnik is a breast oncologist and surgeon who has been in practice for 26 
years.  She has a wealth of experience in research and served as the primary investigator of 
the Grand Rapids Research Consortium of West Michigan (then known as the Grand Rapids 
Clinical Oncology Program) from 2005-2008.  Dr. Melnik has also been a lead physician in 
critical trial accrual for Spectrum Health.  Dr. Melnik will plan to spend about 5% of her time 
on this project.  She will be referring and following patients during the course of this study. 
 
Dr. Jaklitsch is an anesthesiologist who is certified through the American Board of 
Anesthesiology and has been in practice since 2005.  He is presently the Vice-Chairman of 
the Spectrum Health Department of Anesthesiology and has significant previous experience 
with research.  Dr. Jaklitsch will plan to spend 5-10%  of his time on this project, primarily in 
coordination and sharing information with other anesthesiologists who will be doing the 
blocks as part of standard of care. 
 
The other investigators, Dr. Miller, Dr. Oostendorp, Dr. Paulson and Dr. Wright will be 
performing standard of care surgery.  Their direct study involvement will be minimal, but they 
will be helping to screen and refer patients to the study as well as doing the standard of care 
follow-up visit two weeks post-surgery.      
 
Dr. Erica Burkheimer is a general surgery_resident in her second_year of training.  She will 
plan to spend about 5% of her time on this project.   
 
The research study coordinators have clinical research and oncology experience.  The lead 
research coordinator will plan to spend 25-30% of his or her time on this project.  
 
This research project has been vetted by the research department and they have agreed to 
support it with resources.  Physician time for the project is being donated. 
 
8. Study Design: 
a. Recruitment Methods 
Patients will be referred by the Spectrum Health breast surgeons.  If the patient is 
interested, the investigator or research staff will provide a copy of the informed 
consent for the patient to review.  Spectrum Health research staff will then follow up 
with the patients to further discuss the study and confirm that the patient is interested 
in participation.   
 
Patients will then be consented by a clinical research coordinator.  Typically, this 
would occur at the hospital where they will be undergoing their surgery.  The 
coordinator will review the consent with the patient (and family or significant other, as 
applicable) and have the patient sign it.  The coordinator will make all reasonable 
attempts to keep the discussion as private as possible.  In order to minimize 
coercion, it will be made very clear to patients that their participation is strictly 
voluntary and that not choosing to participate will in no way affect their present or 
future care at Spectrum Health.   
 
Once the patient has been randomized to either PEC or PVB, the anesthesiologist 
on call for local blocks will see the patient and review that analgesic plan and the 
risks of that specific procedure with the patient.  This meeting and explanation are 
standard, but they may also answer questions the patient may have related to the 
study.   


 
Page 3 of 9 
 
We anticipate enrolling 128 total patients in the study, 64 in the PVB arm and 64 in 
the PEC arm.   
 
There will be no payment to patients for inclusion in the study.   
 
b. Inclusion and Exclusion Criteria 
Inclusion Criteria: 
i. Female patients ≥ 18 years of age 
ii. Total mastectomy or partial mastectomy with or without reconstruction OR 
planned lumpectomy.   
iii. Patient determined by their surgeon as medically able to receive a regional 
block for post-operative analgesia 
iv. Patient agrees to participate in the study and signs informed consent 
 
Exclusion Criteria: 
i. Neoadjuvent radiation therapy 
ii. Stage IV cancer 
iii. Planned general anesthesia use during surgery 
iv. Allergies to ropivacaine, midazolam, fentanyl, or propofol 
v. Pregnant women 
vi. Prisoners 
vii. Adults unable to consent 
viii. Non-English-speaking patients 
 
c. Study Endpoints 
Primary Outcome Variables:   
Intraoperative narcotic use, Post Anesthesia Care Unit (PACU) narcotic use and 
postoperative narcotic use. We would expect that all variables will have a lower 
values in patients randomized to PEC versus PVB. 
 
Secondary Outcome Variable(s):   
Length of operation, estimated blood loss, incidence of postoperative nausea,  
subjective pain at two weeks (including patient’s overall pain rating for the previous 
two weeks, the patient’s stated last time they used pain pills) and number of calls to 
physician’s office following hospital discharge. 
 
d. Procedures Involved in the Research 
This is a prospective, randomized study.    
Following satisfaction of the inclusion/exclusion criteria and signed informed consent, 
patients will be randomized to paravertebral block or a pectoral nerve block.  The 
randomization schedule will be set-up prior to study start using an Excel 
spreadsheet.  Spectrum Health statisticians designed the randomization schedule to 
meet significance for the endpoints.  Randomization is 1:1, PEC:PVB.  If the patient 
is unwilling to be randomized to one or the other type of block, they will not be able to 
participate in the study.   After each patient is consented, the randomization schedule 
will be checked and the data sheet with the type of block to be used will be placed in 


 
Page 4 of 9 
the patient chart.  The research coordinator will notify anesthesia of which block will 
be used on the patient.  
 
Patients will proceed to surgery per usual standard of care.  The PVB is performed 
along the spine utilizing ultrasound guided technique. The PEC is performed 
anteriorly, at the level of the axillary line, also utilizing ultrasound guided technique. 
Each block will be performed using 20-30 mL 0.5% Ropivacaine1 per side. 
Midazolam and fentanyl will be used for sedation as needed. Intraoperatively, 
patients will undergo monitored anesthesia care with a propofol infusion (50-150 
mcg/kg/min). Additional IV fentanyl will be given as needed. Anesthesia will be 
converted to general anesthesia if the patient is unable to tolerate the procedure with 
sedation and block anesthetic or if general anesthesia is preferred by the surgeon.  
This will not disqualify the patient, but the conversion will be noted in REDCap. 
1Package inserts for these FDA-approved drugs are included as Appendix A to the protocol. 
 
All post-operative care will be standard of care.   
 
Data collected will include the following:   
i. Demographics1 
ii. Medical history2  
iii. Surgical procedure performed & pain control technique(s) used 
iv. Extra doses of narcotic and sedative medication used during surgery.3 
v. Length of surgery 
vi. Duration of hospital stay (measured in minutes)  
vii. Total of extra narcotic and sedative medication used while in PACU and in 
the first 24 hours post-PACU (or until discharge, whichever comes first) 
viii. Total does of anti-nausea medication used while in PACU and in the first 24 
hours post-PACU (or until discharge, whichever comes first).  
ix. Which anesthesiologist performed the procedure 
x. Two-week post-operative visit pain rating (subjective information from the 
patient about their over-all pain rating for the previous two weeks, as well as 
the approximate last time they used pain pills) 
xi. Number of phone calls to the surgeon’s office for concerns about pain in the 
time post-discharge and prior to the office visit. 
1 Include distance the patient lives from the Lemmen-Holton Cancer Pavilion, their self-
reported ethnicity and age.  
2 Include stage of tumor, outpatient chronic use of  narcotics, diagnosis of chronic pain, ASA 
classification, current diagnosis, major comorbidities and BMI.   
3Defined as total amount of narcotic/sedative medication given during surgery, in milligrams,    
 
 
Standard of care follow-up will occur at 2 weeks with the physician who performed 
the surgery.  Patient will be asked about pain pill use; those units will be converted to 
morphine equivalents.  This information may also be obtained through a phone call.     
 
This trial is registered on clinicaltrials.gov  
 
Schedule of Events:   
Study 
Requirements 
Pre-
Surgery 
Visit 
Day of 
Surgery 
PACU 
1st 24 hrs. 
post-surgery 
Post-Surgery Visit (2 wks after 
surgery, +/- 1 week)3 


 
Page 5 of 9 
 
1 Consent may be done either prior to the day or surgery or on the day of surgery, depending on timing and 
patient preference.   
2 Includes patient demographics, medical history, block procedure used (PVB or PEC), method of pain control 
used during surgery, extra narcotic/sedative use during surgery, length of surgery, extra narcotic and sedative  
use in PACU, name/total dosage of narcotic use during post-op hospitalization, duration of hospitalization 
3 Data collected from this time period may be done over the phone as well as at the surgeon’s office.  
 
 
e. Data Management 
Data to be collected are detailed in Appendix B (pdfs of REDCap database for 
this study).  Data will be managed by Spectrum Health research staff and kept in 
a locked cabinet or a limited-access electronic drive.   
 
f. Provisions to Monitor the Data for the Safety of Subjects 
The Principal Investigator will oversee the safety of the study.  This safety 
monitoring will include careful assessment and appropriate reporting of adverse 
events (see “Adverse Events” below).    
 
g. Withdrawal of Subjects 
A patient may be withdrawn from the study prior to the expected completion of 
that subject for failure to adhere to protocol requirements.  Patients may choose 
to withdraw from the study at any time.  Data that have already been collected on 
these patients will still be used. 
The primary investigator may remove a patient at any time from this research 
study if it is felt to be in the best interest of the patient. 
 
9. Statistical Plan: 
a. Sample Size Determination 
The primary outcome variable for this study is the difference in narcotic use 
between the PEC group and the PVB group during the first 24 hours following 
surgery.  If we define a clinically important effect as the mean narcotic use in the 
PVB group is twice that seen for the PEC group, with a standard deviation equal 
to the mean of the PVB group, with α=0.05 and β=0.20, we will be able to detect 
a statistically significant difference with 64 subjects in each group, using the 
unpaired t-test.  Complication rates will also be compared between the two 
Eligibility Criteria 
X 
 
 
 
 
Consent 
X1 
X 
 
 
 
Randomization 
 
X 
 
 
 
Surgery, using 
PEC or PVB 
 
X 
 
 
 
Data Collection2 
 
X 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 


 
Page 6 of 9 
groups, although with an anticipated rate of only 5% in the PVB group, it is 
unlikely with the projected sample size that we will find a statistically significant 
effect for this variable. 
 
b. Statistical Methods 
Summary statistics will be calculated.  Quantitative data will be expressed as the 
mean + SD, while nominal data will be expressed as a percentage.  Comparisons 
between groups for quantitative variables will be performed using the t-test. 
Nominal variables will be evaluated using the Chi-Square test.  The data will be 
analyzed as intention to treat.  Significance will be assessed at p<0.05. 
 
10. Risks to Subjects: 
Risks of both procedures are very low – less than 5% for each risk listed here.   
 
PEC 
a. Vascular puncture  
b. Inadequate analgesia 
c. Intraneural injection, resulting in transient neuropathy 
d. Incomplete nerve block 
e. Infection 
 
PVB 
a. Pneumothorax 
b. Vascular puncture 
c. Incomplete nerve block 
d. Hypotension secondary to intrathecal or epidural spread with subsequent 
sympathetic blockade.   
e. Infection 
 
Possible risks related to either PEC or PVB will be discussed with each patient by the 
anesthesiologist prior to their scheduled surgery and will be address in a separate 
consent form as part of routine care.   
Adverse Events (AEs) 
 
An adverse event is defined as “…an unfavorable and unintended sign, symptom or 
disease associated with a subject’s participation in this research study.”  AEs will be 
monitored until the follow up visit with the surgeon postoperatively. All adverse event 
information will be recorded and the clinical course of each event will be followed until 
resolution, stabilization, or until it has been determined that the study treatment or 
participation is not the cause.   
 
Since pain is an expected side effect of surgery, and we will be monitoring post-op pain 
medication usage and post-op pain levels in research subjects, pain will not, in and of 
itself, be considered an AE for this study.  As defined by the Common Terminology 
Criteria for Adverse Events, Version 4.0 (May 28, 2009), pain will not be considered an 
AE unless it has reached a “Grade 3,” defined as “Severe pain; limiting self-care and 
activities of daily living.” 
 


 
Page 7 of 9 
We will specifically track any instances of track pneumothorax or hypotension, since 
those are potential side effects of PEC.  
   
Serious Adverse Events (SAE’s) 
 
A serious adverse event is defined as “an adverse event that results in death, is life-
threatening, requires initial or prolonged hospitalization, results in a congenital anomaly 
or requires a medical or surgical intervention to prevent permanent impairment or 
damage.”  SAE’s will be reported to the Spectrum Health Institutional Review Board 
(IRB) in accordance with IRB policies and procedures, within five business days.  Copies 
of each report and documentation of Spectrum Health IRB notification and receipt will be 
kept in the study records. 
 
11. Potential Benefits to Subjects: 
There is no direct benefit to the patients that participate in this study.  It is possible that a 
PEC block will offer equal analgesic efficacy in comparison to paravertebral blocks with 
potential reduction in adverse events including pneumothorax and perioperative 
hypotension.  This research may also benefit others in the future by contributing 
information to the body of knowledge about surgical pain control. 
 
12. Provisions to Protect the Privacy Interests of Subjects: 
The study, including potential risks and benefits of treatment, will be discussed 
thoroughly with potential subjects in a space where he/she is comfortable.  Efforts will be 
made to get a copy of the informed consent to the patient ahead of time, so he/she can 
review it at his/her own pace.  The consent will be reviewed and patients (and others, as 
applicable) will be allowed adequate time to ask questions.  Voluntariness will be 
emphasized.  Efforts will be made to keep the discussion private.  Reported data will not 
contain identifiable information.  No vulnerable populations will be included in this study.   
 
13. Provisions to Maintain the Confidentiality of Data: 
Patient data will be entered into an electronic data capture system, created in REDCap.  
Only study staff will have access to these records.  Any paper records will be stored in 
hard copy in a locked filing cabinet in the research office.  Data will be analyzed by the 
Spectrum Health Research Department statistician and will not be sent outside the 
system.  Only study staff will have access to the research data.  Data will be stored after 
study completion per Spectrum Health Research standards.  The collection of sensitive 
information will be limited to the amount necessary to achieve the aims of the research 
study.  Study-related monitoring, audits and inspections by the Spectrum Health IRB and 
government regulatory agencies will be permitted, as required. 
 
All study staff will have training through the Collaborative Institutional Training Initiative 
(CITI), including training on Good Clinical Practice (GCP) practice standards.   
 
 
 
14. Medical Care and Compensation for Injury: 
If patients are injured or made sick from taking part in this research study, medical care 
will be provided in accordance with current standards of care. No funds have been set 


 
Page 8 of 9 
aside to pay the patient in the event of a research related injury. The patients may 
contact the investigator for more information. 
 
15. Cost to Subjects: 
Since both PEC and PVB are both standard of care procedures, costs for the 
surgery, including the blocks, will be billed to the patient and/or their insurance 
company.  Study subjects will be responsible for any co-pays.  Study subjects 
should not incur any extra charges related to the research study. 
 
16. Consent Process: 
The study investigators (Spectrum Health Breast Surgeons) will introduce the study to 
the patients at their pre-surgery visit.  They will fill out and sign an eligibility checklist for 
the research coordinators.  The research coordinators will then reach out to the patient 
to confirm interest in the study and will give the patient a copy of the informed consent, if 
they have not already received one.  The coordinator will then review the consent with 
the patient and family (as applicable).  Adequate time will be allotted for the patient 
and/or family and friends to ask questions.  Enough time will also be allowed for both the 
patient and the coordinator to feel that there is an adequate understanding of the study 
and the responsibilities involved.  Subjects will be informed that the research study is 
voluntary.  If the patient is still interested, they will sign a copy of the research consent.  
A copy of the consent will be given to the patient and a copy will be placed in their 
medical chart. On the morning of surgery, when the anesthesiologist comes in to discuss 
anesthesia and pain control with the patient, he or she will also discuss the research 
study with the patient.   
 
17. Vulnerable Populations: 
This study will not include any vulnerable populations.   
 
18. Sharing of Results with Subjects: 
There are no plans to share study results with the research subjects.   
 
19. References: 
1. Glissmeyer, Johnson, Sherman, et al. Effect of paravertebral nerve block 
on narcotic use after mastectomy. American Journal of Surgery. 2015. 
article in press 
2. Wahba, Kamal. Thoracic paravertebral block versus pectoral nerve block 
for analgesia after breast surgery. Egyptian Journal of Anaesthesia. 
30.129-135. 2014. 
3. Sopena-Zubiria, Fernandez-Mere, Arias, et al. Thoracic paraverteberal 
block compared to thoracic paraverteberal block plus pectoral nerve block 
in reconstructive breast surgery. Revista Espanol De Anestesiologia Y 
Reanimacion. 2012 Jan; 59(1): 12-7 
4. Bashandy, Abbas. Pectoral nerves I and II blocks in multimodal analgesia 
for breast cancer surgery: a randomized clinical trial. Regional Anesthesia 
and Pain Medicine. 2015 Jan; 40(1): 68-74 


 
Page 9 of 9 
5. Study data were collected and managed using REDCap electronic data 
capture tools hosted at Spectrum Health.1  REDCap (Research Electronic 
Data Capture) is a secure, web-based application designed to support 
data capture for research studies, providing 1) an intuitive interface for 
validated data entry; 2) audit trails for tracking data manipulation and 
export procedures; 3) automated export procedures for seamless data 
downloads to common statistical packages; and 4) procedures for 
importing data from external sources. 1Paul A. Harris, Robert Taylor, 
Robert Thielke, Jonathon Payne, Nathaniel Gonzalez, Jose G. Conde, 
Research electronic data capture (REDCap) – A metadata-driven 
methodology and workflow process for providing translational research 
informatics support, J Biomed Inform. 2009 Apr;42(2):377-81.