Role of Continuous Local Infusion of Ropivacaine for Post-Operative Pain Management in Patients Receiving Osseocutaneous Free Flaps
Phase: PHASE2
Conditions: Head and Neck Cancer, Free Tissue Transfer
Sponsor: Icahn School of Medicine at Mount Sinai

Protocol Title: Role of Continuous Local Infusion of Ropivacaine for Post-Operative Pain Management 
in Patients Receiving Osseocutaneous Free Flaps 
PI: Brett Miles, MD 
NCT03349034 
Date: 9/19/2018 

Icahn School of Medicine at Mount Sinai
Mount Sinai Beth Israel
Mount Sinai Brooklyn
The Mount Sinai Hospital
Mount Sinai Queens
New York Eye and Ear Infirmary
of Mount Sinai
Mount Sinai St. Luke's
Mount Sinai West
Program for the Protection
of Human Subjects
Institutional Review Boards
Mount Sinai Health System
One Gustave L. Levy Place, Box
 1081
New York, NY 10029-6574
T 212-824-8200
F 212-876-6789
irb@mssm.edu
icahn.mssm.edu/pphs
Amendment
IRB-17-01893
Brett Miles
Table of Contents
1. Modification.............................................................................................................................................................................1
2. Summary - Title.....................................................................................................................................................................2
3. Summary - Setup..................................................................................................................................................................3
4. Summary - Background......................................................................................................................................................5
5. Research Personnel.............................................................................................................................................................8
6. Sites.......................................................................................................................................................................................... 9
7. Subjects - Enrollment........................................................................................................................................................10
8. Subjects - Populations......................................................................................................................................................11
9. Subjects - Participation.....................................................................................................................................................12
10. Procedures - Narrative...................................................................................................................................................14
11. Procedures - Genetic Testing......................................................................................................................................15
12. Procedures - Details....................................................................................................................................................... 16
13. Procedures - Compensation.........................................................................................................................................17
14. Consent - Obtaining Consent.......................................................................................................................................18
15. Consent - Documents.....................................................................................................................................................19
16. Data - Collection...............................................................................................................................................................20
17. Data - Storage.................................................................................................................................................................. 22
18. Data - Safety Monitoring................................................................................................................................................25
19. Drugs / Biologics..............................................................................................................................................................27
20. Financial Administration................................................................................................................................................. 28
21. Attachments....................................................................................................................................................................... 29

IRB-17-01893
Amendment
Brett Miles
1. Modification
Summary of the Modification Request
serum ropivacaine levels will not be monitored.
Spanish consent form has been updated to remove serum level monitoring
Justification for the Modification
After consulting with Sinai Anesthesia Pain Service and the literature* it is clear that this was not needed. It is
 not standard to monitor these levels with infusion and previous studies were done to demonstrate that it wasn't
 necessary previously. Further, several studies have been done without monitoring the levels. The amount of
 Ropivacaine we are infusing is too low to reach systemic toxicity levels. 
This Modification Changes
 the Consent Document or
 Information that May Affect
 Subjects’ Willingness to Continue
 to Participate in the Research
Yes
Description of Changes in the Consent Document or Information that May Affect Subjects’ Willingness to
 Continue to Participate in the Research
serum ropivacaine levels will not be monitored and has been removed from the consent.
Subjects Will Be Re-Consented or
 Provided with the New Information
Yes
Proposed Plan to Re-Consent Subjects or to Provide Them with the New Information
All subjects will be re-consented during their follow-up visits.  
Explanation Why Re-Consenting or Providing Subjects with the New Information is Not Necessary
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2. Summary - Title
Protocol Title
Role of Continuous Local Infusion of Ropivacaine for Post-Operative Pain Management in Patients Receiving
 Osseocutaneous Free Flaps
Principal Investigator
Brett Miles
When the application is complete, it will be sent to the PI for submission
When the application is complete, it will be sent to the PI for submission
Primary Department
Otolaryngology
When the application is complete, it will be sent to the PI for submission
Application Initiated By
Leslie Waters-Martin
Lay Summary
Head and neck oncologic surgery often requires the use of free tissue transfer, or microvascular reconstruction, to
 reconstruct defects created by tumor resections. Although there are several techniques for the reconstruction of
 defects, resection of large tumors leave defects that require the transfer of vascularized tissue from one part of the
 body to repair the defect. For example, the removal of a segment of diseased mandible requires free tissue transfer
 containing the component parts - skin, muscle, and bone - to reconstruct the deficit created by the resection of the
 tumor. Over the years, microvascular surgeons have focused their attention on maximizing the success of these
 technically difficult surgeries. However, now, with free flap reconstruction rates in excess of 95%, surgeons are
 afforded the opportunity to turn their focus toward the morbidities associated with these surgeries. While much has
 been published about donor site wound healing, pain control in the post-operative period has largely been neglected
 in the head and neck reconstruction literature. Systemic analgesia with opioids is standard of care, which has
 been shown to lead to increased confusion, significantly increased length of stay and increased risk of pulmonary
 complications (Oderda et al., Pizzi et al.). In addition, it has been shown that early mobilization and optimal wound
 care can decrease donor site morbidity.
In this study we aim to better control donor site pain utilizing local, targeted analgesia to relieve pain at the donor
 site for osseocutaneous free-flaps. To reduce confounding and bias, the study will be a double-blind prospective
 randomized placebo controlled trial wherein patients undergoing osseocutaneous free flap surgery will be
 randomized to receive continuous infusion of ropivacaine or normal saline (placebo) via intraosseous catheter, which
 will be placed intraoperatively at the time of donor site closure. Patients' pain will be monitored for the first 48hrs after
 surgery. Donor site and global pain at rest will be evaluated every 8 hours for the first two postoperative days using
 a standard pain assessment via a numeric pain scale (0-10). Median daily opiate use via PCA will also be tracked.
 Donor site-specific range of motion and strength will be assessed with a formal physical therapy evaluation on post-
operative day 2 or soonest non-holiday weekday. Information on patient satisfaction, time to ambulation, and length
 of stay will also be collected. Subgroup analysis will be performed.
IF Number
IF2027486
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3. Summary - Setup
Funding Has Been Requested /
 Obtained
No
Application Type
Request to Rely on Mount Sinai IRB
Research Involves
Prospective Study ONLY
Consenting Participants
Yes
Requesting Waiver or Alteration
 of Informed Consent for Any
 Procedures
No
Humanitarian Use Device (HUD)
 Used Exclusively in the Course of
 Medical Practice
No
Use of an Investigational Device to
 Evaluate Its Safety or Effectiveness
No
Banking Specimens for Future
 Research
No
Cancer Related Research that
 Requires Approval from the
 Protocol Review and Monitoring
 Committee (PRMC).
No
   Is this Cancer Related Research?  Cancer Related Research is defined as research that
 has cancer endpoints or has a cancer population as part of or all of its targeted population.
 This includes protocols studying patients with cancer or those at risk for cancer.
  
Clinical Trial
Yes
   
   * A prospective biomedical or behavioral research study of human subjects that is
 designed to answer specific questions about biomedical or behavioral interventions
 (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). 
   *  Used to determine whether new biomedical or behavioral interventions are safe,
 efficacious, and effective.    
  
Drugs / Biologics 
Yes
   
   * Drugs / Biologics That Are Not a Part of Standard Practice 
   * Controlled Substances 
   * Drugs / Biologics Supplied by the Research Sponsor or Purchased with Study Funds 
  
   Ionizing Radiation for imaging or therapy, including X-Ray, Fluoroscopy, CT, Nuclear
 Medicine, PET andor Radiation Therapy:
  
* Purely for standard of care:
Yes
* In frequency or intensity that
 exceeds what is necessary for
 standard of care:
No
Hazardous Materials
No
   * Recombinant DNA 

   * Viral Vectors 
   * Plasmids 
   * Bacterial Artificial Chromosomes 
   * Toxic Chemicals, Potentially Toxic Medications, Carcinogens 
   * Autologous Cell Lines 
  
Request Use of Clinical Research
 Unit Resources
No
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4. Summary - Background
Objectives
Research Question: Can continuous infusion of ropivacaine improve donor site pain control at rest compared to
 placebo in the post-operative period?
Hypothesis 1: Continuous infusion of ropivacaine will improve donor site pain control at rest compared to placebo in
 the post-operative period
Hypothesis 2: Continuous infusion of ropivacaine will improve patients ability to achieve PT milestones compared to
 placebo in the post-operative period
Objectives:
1) Determine whether there is a significant difference in donor site pain at rest with continuous infusion of ropivacaine
 vs saline at the donor site. Pain will be assessed globally and specifically at the donor site.
- Pain will be assessed every 8 hours for the first 48 hours using a numeric pain scale (0-10) at rest.
- Time of extubation will be considered time zero. Then every 8 hours after that time, the patient will have their pain
 assessed. A total of 6 pain assessments will be performed in the 48 hour period.
- A numeric pain scale will be used to rate patient level of pain. 
- The patients subjective pain will be tested and recorded at rest, with no intervention. Patients will be asked their
 global, or overall, pain level. They will then be asked their pain at the donor site specifically. 
2) Patients will be given standard of care opiates via PCA.
Patients will be provided a dilaudid PCA, set for low dose, opioid naïve patients. 
- The amount of opiates required by patients with continuous infusion ropivacaine vs saline placebo will be recorded
3) Determine whether there is an association between continuous infusion of ropivacaine vs saline at the donor site
 and achievement of PT milestones
- At post-operative day 2 (or soonest non-holiday weekday if surgery is performed on Friday), patients will receive a
 physical therapy evaluation where patients will be compared on basic physical therapy milestones.
- Distance able to ambulate, range of motion, strength - standard measures already obtained during standard
 physical therapy consultation. Distance able to ambulate will be measured in feet. Range of motion is a descriptive
 variable (within normal limits, within functional limits, etc.). Strength is measured on the standard neurological
 strength scale out of 5. 
- Total length of stay will be compared between groups to look for a correlation between continuous infusion
 ropivacaine pain control and decreased length of stay
4) Determine whether there is an association between continuous infusion ropivacaine pain control vs saline placebo
 and patient satisfaction
- A standardized pain satisfaction survey (see attachments) will be distributed to patients prior to discharge rating
 their overall satisfaction with postoperative recovery from osseocutaneous free flap
Purpose:
The purpose of the study is to determine whether infusion of ropivacaine vs saline at the donor site will significantly
 decrease donor site pain and whether there is any correlation between pain control, achievement of PT milestones,
 length of stay, and patient satisfaction.
Background
Free flap reconstruction success rates have reached >95%, allowing surgeons to focus on minimizing morbidity
 associated with the surgery. There has been a great deal of literature focused on donor site wound healing including
 the use of negative pressure wound therapy, skin grafts, and local rotational and advancement flaps. However, there
 is scant high quality evidence about donor site morbidity in ossecutaneous free flaps. In particular the literature is
 lacking on donor site pain management outside of standard intravenous analgesia (PCA pump, IV push, etc.)
Donor site pain is a known complication of osseocutaneous free flaps (Klein et al, Harris et al). One study found that
 out of forty procedures with the highest pain scores (median numeric rating scale, 6–7) twenty-two were orthopedic/
trauma procedures on the extremities (Gerbershagen et al), which are the most frequent donor sites for head and
 neck free flap reconstruction. A specific example from orthopedics is the use of iliac crest bone grafts for spine

 arthrodesis procedures. These bone grafts are associated with immediate donor site postoperative pain and difficulty
 ambulating, persistent donor site pain at >3 months in 26% of patients, and functional impairment (Silber et al. 2003).
 Indeed, donor site pain may restrict mobility, preventing adequate rehabilitation and early ambulation resulting in co-
morbidities such as VTE, pneumonia and pressure ulcers (Oderda et al., Pizzi et al.). In addition, early rehabilitation
 may also prevent gait disturbance long term or site-specific functional deficits and allow for participation in physical
 therapy protocols.
The mainstay of postoperative pain management in patients receiving osseocutaneous free flaps is opioids. Opioids
 carry a variety of risks including decreased mobility leading to complications such as DVT and decreased respiratory
 drive leading to pneumonia. As such, alternative pain control methods are preferred for early ambulation and
 recovery. There is evidence in other surgical fields that the use of donor site catheter-based analgesia may alleviate
 pain at the donor site.  There have been several small trials in the orthopedic and craniofacial surgery literature
 that have evaluated the use of long acting anesthetic agents for pain control in iliac crest bone grafts (Singh 2005,
 Singh 2007, Brull 1992, Sbitany 2010, Meara 2011, Samartzis 2016). Although results vary with respect to patient
 reported pain score, patient satisfaction, and hospital stay, three out of four studies reported decreased opioid usage
 when receiving local anesthesia versus no pain control (Singh 2005, Singh 2007, Meara 2011, Brull 1992, Sbitany
 2010, Samartzis 2016). Further, prior studies have postulated that the use of local anesthesia may prevent the
 development of chronic post-operative pain by blocking nociceptive stimuli and suppressing the hyperexcitable state
 in the central nervous system (Tverskoy 1990). As a result, the benefits of donor site analgesia in the post-operative
 period may extend beyond the length of their use.
         
The research design utilized in this study is not unique, and in fact has been utilized in the fields of orthopedic and
 plastic surgery to study the use of donor site analgesia (Blumenthal et al., Heller et al.). We seek to replicate the
 double-blind placebo controlled trial design to evaluate the use of donor site catheter-based analgesia to minimize
 the morbidity associated with head and neck reconstructive surgery donor site pain.
1. Brull SJ, Lieponis JV, Murphy MJ, Garcia R, Silverman DG. Acute and long-term benefits of iliac crest donor site
 perfusion with local anesthetics. Anesthesia and analgesia. Jan 1992;74(1):145-147.
2. Blumenthal, Stephan, Alexander Dullenkopf, Katharina Rentsch, and Alain Borgeat. "Continuous Infusion of
 Ropivacaine for Pain Relief after Iliac Crest Bone Grafting for Shoulder Surgery." Anesthesiology 102.2 (2005):
 392-97.
3. Gerbershagen, Hans J., Sanjay Aduckathil, Albert J. M. Van Wijck, Linda M. Peelen, Cor J. Kalkman, and Winfried
 Meissner. "Pain Intensity on the First Day after Surgery." Anesthesiology 118.4 (2013): 934-44.
4. Harris BN, Bewley AF. Minimizing free flap donor-site morbidity. Current opinion in otolaryngology & head and
 neck surgery. Oct 2016;24(5):447-452.
5. Fiser  DH. Intraosseous Infusion. New England Journal of Medicine. 1990;322(22):1579-1581.
6. Joshi A, Kostakis GC. An investigation of post-operative morbidity following iliac crest graft harvesting. Br Dent J.
 02/14/print 2004;196(3):167-171.
7. Klein S, Hage JJ, Woerdeman LA. Donor-site necrosis following fibula free-flap transplantation: a report of three
 cases. Microsurgery. 2005;25(7):538-542; discussion 542.
8. Loeffelbein, Denys J. et al. "Reduction of Donor Site Morbidity of Free Radial Forearm Flaps: What Level of
 Evidence Is Available?" Eplasty 12 (2012): e9.
9. Luck RP, Haines C, Mull CC. Intraosseous access. J Emerg Med. 2010;39.
10. Meara DJ, Livingston NR, Sittitavornwong S, et al. Continuous infusion of bupivacaine for pain control after
 anterior iliac crest bone grafting for alveolar cleft repair in children. The Cleft palate-craniofacial journal : official
 publication of the American Cleft Palate-Craniofacial Association. Nov 2011;48(6):690-694.
11. Oderda, G. M., Q. Said, R. S. Evans, G. J. Stoddard, J. Lloyd, K. Jackson, D. Rublee, and M. H. Samore.
 "Opioid-Related Adverse Drug Events in Surgical Hospitalizations: Impact on Costs and Length of Stay." Annals of
 Pharmacotherapy 41.3 (2007): 400-06.
12. Petitpas F, Guenezan J, Vendeuvre T, Scepi M, Oriot D, Mimoz O. Use of intraosseous access in adults: a
 systematic review. Critical Care. 2016;20(1):102.

13. Pizzi, Laura T., Richard Toner, Kathleen Foley, Erin Thomson, Wing Chow, Myoung Kim, Joseph Couto,
 Marc Royo, and Eugene Viscusi. "Relationship Between Potential Opioid-Related Adverse Effects and Hospital
 Length of Stay in Patients Receiving Opioids After Orthopedic Surgery." Pharmacotherapy: The Journal of Human
 Pharmacology and Drug Therapy 32.6 (2012): 502-14.
14. Rosetti VA, Thompson BM, Miller J, Mateer JR, Aprahamian C. Intraosseous infusion: an alternative route of
 pediatric intravascular access. Annals of emergency medicine. Sep 1985;14(9):885-888.
15. Silber JS, Anderson DG, Daffner SD, et al. Donor site morbidity after anterior iliac crest bone harvest for single-
level anterior cervical discectomy and fusion. Spine (Phila Pa 1976). Jan 15 2003;28(2):134-139.
16. Singh K, Samartzis D, Strom J, et al. A prospective, randomized, double-blind study evaluating the efficacy of
 postoperative continuous local anesthetic infusion at the iliac crest bone graft site after spinal arthrodesis. Spine
 (Phila Pa 1976). Nov 15 2005;30(22):2477-2483.
17. Singh K, Phillips FM, Kuo E, Campbell M. A prospective, randomized, double-blind study of the efficacy of
 postoperative continuous local anesthetic infusion at the iliac crest bone graft site after posterior spinal arthrodesis: a
 minimum of 4-year follow-up. Spine (Phila Pa 1976). Dec 01 2007;32(25):2790-2796.
18. Sbitany H, Koltz PF, Waldman J, Girotto JA. Continuous bupivacaine infusion in iliac bone graft donor sites to
 minimize pain and hospitalization. The Cleft palate-craniofacial journal : official publication of the American Cleft
 Palate-Craniofacial Association. May 2010;47(3):293-296.
19. Samartzis D, Bow C, Cheung JP, et al. Efficacy of Postoperative Pain Management Using Continuous Local
 Anesthetic Infusion at the Iliac Crest Bone Graft Site in Patients with Adolescent Idiopathic Scoliosis: A Parallel,
 Double-Blinded, Randomized Controlled Pilot Trial. Global spine journal. May 2016;6(3):220-228.
20. Tverskoy, M., Cozacov, C., Ayache, M., Bradley, E. L., Jr., & Kissin, I. (1990). Postoperative pain after inguinal
 herniorrhaphy with different types of anesthesia. Anesth Analg, 70(1), 29-35.
 
 
Primary and Secondary Study Endpoints
Primary Study Endpoint: Median postoperative pain score on a 10 point numeric pain scale, recorded over the 48
 hours.
Secondary Study Endpoints:  total opiate consumption, achievement of physical therapy milestones, patient
 satisfaction, and side effects of opiates (nausea/vomiting, pruritus)
Primary Safety Endpoints: Infection at the site of local infusion catheter, donor site hematoma, seroma, wound
 dehiscence, compartment syndrome, and ropivacaine toxicity or allergy
Protocol Was Already Approved
 by the Icahn School of Medicine at
 Mount Sinai (ISMMS) Institutional
 Review Board (IRB) Under a
 Different Principal Investigator
No
Protocol Was Previously Submitted
 to an External(non-ISMMS) IRB
No
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5. Research Personnel
Name/Department
Role/Status
Contact
Access
Signature
 Authority
Phone
Email
Brett Miles /
 Otolaryngology
Principal
 Investigator / 
Signature
 Authority
Leslie Waters-
Martin / 
ARA / 
Signature
 Authority
Scott Roof / 
CI / 
Edit
 Access
Rocco Ferrandino / 
CI / 
Edit
 Access
Samuel DeMaria / 
CI / 
Read-only
 Access
Yury Khelemsky / 
CI / 
Read-only
 Access
Caroline Eden / 
CI / 
Edit
 Access
Marita Teng / 
CI / 
Read-only
 Access
Eric Genden / 
CI / 
Read-only
 Access
Darejan
 Gogveridze / 
CI / 
Edit
 Access
Annika Meyer / 
CI / 
Read-only
 Access
Joshua Rosenberg / CI / 
Read-only
 Access
Mike Yao / 
CI / 
Read-only
 Access
Nicolette Florio / 
ARA / 
Edit
 Access
 
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6. Sites
Site Name
The Mount Sinai Hospital
Other External Site Name
Contact Details
Approved
Approval Document
Funded By Mount Sinai
Other IRB
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7. Subjects - Enrollment
Site Name
The Mount Sinai Hospital
Subjects To Be Enrolled
40
Total Number of Subjects to be
 Enrolled Across All Listed Sites
 Above (Auto Populated)
40
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8. Subjects - Populations
Inclusion Criteria
1) Patients receiving osseocutaneous free tissue transfer regardless of the indication for free tissue transfer. This
 includes osseocutaneous tissue from fibula and scapula 
2) Age # 18
Exclusion Criteria
1) Patients unable to understand the research protocol and/or provide informed consent
2) Patients under the age of 18
3) Patients with a history of allergic reaction to ropivacaine or other local amide anesthetics
4) Patients whose participation in this trial would require exclusion from participation in another clinical research trial
 related to the patient's malignant diagnosis.
5) Patients with previous pain disorders or drug abuse requiring chronic narcotic use.
6) Vulnerable populations (adults unable to consent, individuals who are not yet adults, wards of the state, prisoners)
Enrollment Restrictions Based
 Upon Gender, Pregnancy,
 Childbearing Potential, or Race
No
Age Range(s)
18 to 64 Years, 65 Years and Over
Targeted Population(s)
Adults - Patients 
Other Aspects that Could Increase Subjects Vulnerability
Access to personal health information; however, all research data will be viewed only by research team members,
 and all data will be encrypted and password protected and stored on a Mount Sinai hospital computer located in the
 Otolaryngology Resident Library on the 10th floor of the Annenberg building. The library is locked at all times and
 requires a password for entry. 
Safeguards to protect Subjects rights and welfare
Data obtained in this project will be in the form of an excel spreadsheet. All data will be de-identified and labeled with
 a unique code, and kept on a password-protected hard drive at the Mount Sinai Medical Center. The names of the
 patients will not be released to any outside organizations or to persons not involved with the investigation. They will
 not be revealed in written reports or publications detailing the research findings. 
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9. Subjects - Participation
Duration of an Individual Subjects Participation in the Study
Participation in this research study is expected to last the duration of the patient's initial post-surgical hospital stay, or
 a total of approximately 1 week from the time of surgery. The infusion catheter will be removed on post-operative day
 2 (48 hours after surgery). A physical therapy evaluation will happen on post-operative day 2 (or soonest available
 non-holiday weekday, if surgery is performed on Friday), as is standard of care. Additionally, patients will be asked to
 complete a survey regarding their satisfaction with pain control prior to discharge. 
Duration Anticipated to Enroll All Study Subjects
24 months
Estimated Date for the Investigators
 to Complete This Study
Within two years
Procedures for Subjects to Request Withdrawal
Enrolled subjects may decide to withdraw from the study at any time in the post-operative period, in which case the
 infusion catheter will be removed, and standard of care pain assessment and control methods continued.
The rate of patient withdrawal will be continuously reviewed during the study to analyze for any adjustment that might
 be required to our sample size and to perform the appropriate statistical analyses of the data collected.
Procedures for Investigator to Withdraw Subjects
Previously enrolled subjects who do not meet inclusion criteria due to an an intraoperative decision will be removed
 from the study. For instance, if an initially planned free tissue transfer reconstruction is forgone for a local-regional
 flap reconstruction the subject will no longer meet criteria for inclusion into the study. Once patients are withdrawn, a
 record of the signed consent form along with the reason for withdrawal will be stored and filed.
Enrolled patients who fail to have a successful placement of donor site catheter will be withdrawn from the study. 
Participants Will Be Recruited
Yes
Recruitment Method(s)
Clinical Practice
How Participants Will Be Identified
Patients presenting to the Tisch Cancer Institute or the Department of Otolaryngology Head and Neck Surgery for a
 pre-operative evaluation whom meet inclusion criteria will be recruited at the time of their visit. 
Who Will Initially Approach
 Potential Participants
Study Personnel, Treating Physician, Clinic
 Personnel
How Research Will Be Introduced to Participants
All patients presenting to the Tisch Cancer Institute or the Department of Otolaryngology Head and Neck Surgery
 will be screened for satisfaction of inclusion and exclusion criteria by the attending head and neck surgeon during
 routine history and physical examination during their regularly scheduled preoperative visit. Once identified, the
 patient will be approached by the attending physician to discuss the research and obtain consent. If amenable,
 the patient may be directed to further discuss the study and answer any additional questions or concerns with a
 member of the research team. If the patient wishes to have more time to think about his/her participation in the study,
 he/she will be given the consent form and asked to fill it out at a time of his/her own convenience. Should he/she
 choose to participate, the patient will be instructed to bring the completed consent form with him/her on the date of
 his/her surgery. Should a patient elect to have more time to decide on his/her participation (as outlined above), a
 member of the research team will call them within a week of the date of the scheduled surgery to remind them to
 bring the consent form, should he/she wish to participate, and answer any additional questions at that time. No new
 information or discussion of the study will be provided on the date of surgery. If a patient is identified for participation
 in the study during an inpatient hospitalization, the patient will be approached about the study by the attending
 physician or member of the research team at least two days prior to the date of the surgery. 
How Participants Will Be Screened
Participants will be identified based on the history and physical exam performed by the Otolaryngology attending or
 resident

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10. Procedures - Narrative
Description of the Study Design
To reduce confounding and bias, the study will be a double-blind prospective randomized placebo controlled trial
 wherein patients undergoing osseocutaneous free flap surgery will be randomized to receive continuous infusion of
 ropivacaine or normal saline (placebo) via intraosseous catheter, which will be placed intraoperatively at the time of
 donor site closure. 
Description of Procedures Being Performed
Intraoperatively, following procurement of the fibula or scapula bone graft and at the time of surgical wound closure,
 all patients will receive the placement of a continuous infusion catheter into the donor site wound bed. The infusion
 reservoir will be connected to a catheter-based On-Q pump, and the catheter will be placed in the donor site. A
 stab incision separate from the surgical wound will be used to bring the catheter through the skin. Patients will
 be randomized to receive 6 ml/hr of 0.2% Ropivacaine or 6 ml/hr of normal saline via the infusion reservoir. The
 catheter will be left in place with continuous infusion for first 48 hours of the post-operative period. The catheters will
 be removed by the housestaff on POD2. There is minimal risk to removing the OnQ catheter. Any opening in the skin
 will be covered with gauze to allow primary healing. Solutions of saline and ropivacaine will be prepared and made
 available for infusion by the Mount Sinai Pharmacy. Solutions will be blinded, and identical in appearance. Patients
 will be assigned to ropivacaine or saline intervention by the research pharmacy through coded envelopes. Patients,
 physicians, nurses, and research personnel will be blinded to treatment assignment. Every 8 hours for the first 48
 hours, patients will be asked to complete a visual analogue scale (VAS) for reporting their pain. The VAS will be
 performed six times over the course of the 48hrs. These will be performed during regular flap check monitoring, to
 ensure patients are not disrupted additional times throughout the day for this study.
Prior to discharge from the hospital, the study subjects will be asked to complete a brief survey (APS-POQ-R Pain
 Survey) regarding their experience, with regard to pain management. 
Description of the Source Records that Will Be Used to Collect Data About Subjects 
The source records used will come from the electronic medical records of patients at the Mount Sinai Hospital.
 The electronic medical record system used at MSH is Epic. The information collected will be age, race, sex, BMI,
 comorbid conditions, tumor grade/stage, operative time, length of stay, ASA status, intra-operative analgesic use,
 post-operative opioid use, Ropivacaine levels, time to PCA removal, pain scores, time and distance of ambulation,
 strength, and the standard physical therapy evaluation.
Description of Data that Will Be Collected Including Long-Term Follow-Up
1) Donor site specific and global pain scores using the visual analogue scale (VAS) will be collected every 8 hours
 for the first 2 postoperative days. The VAS pain scale will be measured and recorded by a member of the research
 team.
2) Opioid usage will be collected by interrogating the PCA pumps during the first 2 postoperative days. 
3) Physical therapy milestones will be assessed on the second postoperative day (or soonest non-holiday weekday, if
 surgery is performed on Friday) by formal physical therapy evaluation.
4) A standardized pain satisfaction survey will be distributed and recorded prior to discharge
Research Requires HIV Testing
No
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11. Procedures - Genetic Testing
Genetic Testing Will Be Performed
No
Guidance and Policies > Future Use Data Sharing and Genetic Research
  
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12. Procedures - Details
Surveys or Interviews
Yes
Type of Instruments Being Used
Standardized
Names of Standardized Instruments
APS-Patient Outcome Questionnaire (APS-POQ-R)
Audio / Photo / Video Recording
No
Deception
No
Results of the Study Will Be Shared
 with Subjects or Others
No
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13. Procedures - Compensation
Compensation for Participation
No
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Amendment
Brett Miles
14. Consent - Obtaining Consent
Consent Process
Adult Consent
Where and When Consent Will Be Obtained
Patients presenting to the Tisch Cancer Institute or the Department of Otolaryngology Head and Neck Surgery for a
 pre-operative evaluation whom meet inclusion criteria will be recruited at the time of their visit. During the risk and
 benefits discussion of surgical intervention led by one of our attending surgeons, a brief scripted description of the
 use of continuous local analgesia will be included and the patient given the option to consent for its use either during
 the same visit, at a follow up appointment, or the day of surgery. If a patient is missed during their clinic visit and is
 scheduled for a procedure that meets inclusion criteria he/she will be contacted prior to the surgery date to be made
 aware of the study. He/she will then be consented at the date of surgery prior to entering the operating room. The
 operating schedules of the entire Head and Neck Division are reviewed on a weekly basis. Patients pre-admitted
 prior to their surgery, who meet inclusion criteria, will be recruited at a private inpatient hospital setting at least one
 day prior to their surgery.
Waiting Period for Obtaining Consent
There will be no minimum waiting period between informing the subject and obtaining consent. However, all patients
 will be informed of the study at an appointment prior to the day of surgery or at least 2 days prior to the date of
 surgery should the patient be identified during an inpatient hospitalization.
SOP HRP-090 Informed Consent
 Process for Research Is Being
 Used
Yes
PPHS Worksheets, Checklists and SOPs
  
Process to Document Consent in
 Writing
Will Use Standard Template
Non-English Speaking Participants
 Will Be Enrolled
Yes
What Languages Other Than English Will Be Used
Spanish and Chinese comprise the majority of Mount Sinai patients who are non-English speaking. All patients will be
 consented in their primary or native language, using a translator service (either in person or via telephone).
What Process Will Be Used
Long Form
  
  The consent document must be translated into the language of the potential subject, and
 approved by the IRB, before you can go through the consent process with the non-English
 speaking person. If, after the project is approved, a short form consent process is needed,
 please see the PPHS policy and submit a modification.
     
 
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IRB-17-01893
Amendment
Brett Miles
15. Consent - Documents
Consent Documents
Type
The Mount Sinai Health System Consent
 Form to Volunteer In A Research Study And
 Authorization For Use and Disclosure Of
 Medical Information
Name
Role of Continuous Local Infusion of
 Ropivacaine for Post-Operative Pain
 Management in Patients Receiving
 Osseocutaneous Free Flaps 
Upload
Ideate Consent Form Spanish Version.docx
Type
IdeateHRP-502 MSHS Template Consent for
 Adult Subjects 
Name
Role of Continuous Local Infusion of
 Ropivacaine for Post-Operative Pain 
Upload
Ideate HRP-502a MSHS Template Consent
 for Adult Subjects. V3 clean 7 .3.17.doc
Type
IdeateHRP-502 MSHS Template Consent for
 Adult Subjects 
Name
Role of Continuous Local Infusion of
 Ropivacaine for Post-Operative Pain 
Upload
Ideate HRP-502a MSHS Template Consent
 for Adult Subjects. V3 tracked 7 .3.17.doc
Type
Ideate HRP502 Spanish Consent for Adult
 Subjects
Name
Role of Continuous Local Infusion of
 Ropivacaine for Post-Operative Pain
Upload
Ideate Consent Form Spanish Version.docx
Consent Templates
  
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IRB-17-01893
Amendment
Brett Miles
16. Data - Collection
Health Related Information Will Be
 Viewed, Recorded, or Generated
Yes
Description of Health Information That Will Be Viewed, Recorded, or Generated
The information collected will be BMI, comorbid conditions, tumor grade/stage, ASA status, intra-operative analgesic
 use, post-operative opioid use, Ropivacaine levels, time to PCA removal, pain scores, time and distance of
 ambulation, strength, and the standard physical therapy evaluation.
Non-Health Related Information Will
 Be Viewed or Recorded
Yes
Description of Non-Health Information That Will Be Viewed or Recorded
Age, race, sex, operative time, date and length of stay 
HIV / AIDS Related Information Will
 Be Viewed or Recorded
No
Data That Will Be Viewed,
 Recorded, or Generated Contains
 ANY of the Following Directly
 Identifiable Information
No
  
  * Name 
  * Social Security Number 
  * Medical Record Number 
  * Address by Street Location 
  * Telephone Number 
  * Fax Number 
  * Web Uniform Resource Locators (URLs) 
  * Internet Protocol (IP) Address 
  * Health Plan Beneficiary Number 
  * Account Number 
  * Certificate 
  * License Number 
  * Vehicle Identification Number (Including License Plate Numbers) 
  * Full-Face Photographic Images 
  * Biometric Identifiers (Finger and Voice Prints) 
  * Geographical Subdivisions Smaller Than a State 
  * All Elements of Dates for Dates Directly Related to an Individual (i.e., Birth Date,
 Admission Date, Discharge Date) 
     * Email Address 
     
 
Data Collection Sheet
        
        A Data Collection Sheet is required if you are either performing a retrospective review,
 or your study meets the category of exempt 4 research, or your study meets the category
 of expedited 5 research. Please upload it here.
        
    
Data Collection Source(s)
Participant, Medical Chart (Paper or
 Electronic)

Page 21 of 29

IRB-17-01893
Amendment
Brett Miles
17. Data - Storage
Location Where Data Will Be Stored
All data points will be maintained on a database created for this study using Microsoft Excel or HIPAA-compliant
 spreadsheet. This database will only be accessible by the research personnel listed in the IRB by using password-
protected hard drive at Mount Sinai as well as encrypted email (Mount Sinai emailing system). To maintain
 confidentiality all personal identifiable information will be removed from the database and labeled with a unique code.
 Consent forms for the study will be kept in a secure locked cabinet at our department. The data obtained from this
 study will be maintained indefinitely but only accessible by the investigators/coordinators on this study who are all
 HIPPA trained.
How will the data be stored?
With a Code That Can Be Linked to the
 Identity of the Participant
Research Personnel Responsible
 for:
Brett Miles
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Yes
Research Personnel Responsible
 for:
Leslie Waters-Martin
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
Yes
Research Personnel Responsible
 for:
Scott Roof
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Rocco Ferrandino
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Samuel DeMaria
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Yury Khelemsky
Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Caroline Eden

Accessing Data
Yes
Receipt or Transmission of Data
Yes
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Marita Teng
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Eric Genden
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Darejan Gogveridze
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Annika Meyer
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Joshua Rosenberg
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Mike Yao
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Research Personnel Responsible
 for:
Nicolette Florio
Accessing Data
No
Receipt or Transmission of Data
No
Holding Code That Can Be Linked
 to Identity of Participants
No
Duration Data Will Be Stored
The data obtained from this study will be maintained indefinitely but only accessible by the investigators/coordinators
 on this study who are all HIPPA trained.
Steps That Will Be Taken to Secure the Data During Storage, Use, and Transmission
This database will only be accessible by the research personnel listed in the IRB by using password-protected
 hard drive at Mount Sinai as well as encrypted email (Mount Sinai emailing system). To maintain confidentiality all

 personal identifiable information will be removed from the database and labeled with a unique code. Consent forms
 for the study will be kept in a secure locked cabinet at our department. 
Data Analysis Plan Including Any Statistical Procedures
Intra- and inter-patient pain scores are expected to be highly variable and non-normally distributed, thus median
 pain score after 6 measurements will be reported for each enrolled subject. Non-parametric Wilcoxon rank-sum
 test will be used to compare treatment groups. A sample size of 15 in each group will have 80% power to detect a
 probability of 0.800 that a pain score in the local anesthesia group is less than a pain score in the placebo group
 using a Wilcoxon (Mann-Whitney) rank-sum test with a 0.050 two-sided significance level. We will aim to recruit 20
 patients per treatment group to account for patient drop out.
Information on patient demographics, patient satisfaction, time to ambulation, and length of stay will also be collected.
 Subgroup analysis will be performed.
Page 24 of 29

IRB-17-01893
Amendment
Brett Miles
18. Data - Safety Monitoring
More Than the Minimum Data
 Safety Monitoring Will Be Done
Yes
Principal Monitor
Brett Miles
Additional Monitors
Name
Samuel DeMaria
Title
Instructor
Department
Anesthesiology
Contact Details
Work1 Gustave L Levy PlaceNew
 YorkNY10029
Type
Name
Marita Teng
Title
Assistant Professor
Department
Otolaryngology
Contact Details
WorkOne Gustave L. Levy PlaceNew
 YorkNY10029
Type
Name
Yury Khelemsky
Title
Assistant Professor
Department
Anesthesiology
Contact Details
WorkOne Gustave L. Levy PlaceNew
 YorkNY10029
Type
Specific Items That Will Be Monitored for Safety
Patient reported adverse events related to toxicity of Ropivacaine.  
Patients will be monitored for signs and symptoms of Ropivacaine toxicity including but not limited to metallic taste,
 tinnitus, nausea, vomiting, seizures, cardiac arrhythmias, and cardiovascular collapse. 
Frequency of Data Review
The DSMC will meet bi-annually and/or more often if required to review data safety.
Rules for Alteration of Study Design
In the event of toxicity, catheter system will be
immediately removed and the acute pain service will escalate care as indicated.
Selection Procedures to Minimize Toxicity
Patients with a history of allergic reaction to Ropivacaine or other local amide anesthetics will not be enrolled in the
 study., Additionally, patients with previous pain disorders or drug abuse requiring chronic narcotic use will not be
 enrolled in the study. 
Grading System to Evaluate Adverse Events
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events
 (CTCAE) version 4.0 will be utilized for AE reporting. 
Procedures to Assure Data Accuracy
The selected principle monitor has established relationships with the subjects that will enable him to identify risks
 to the subjects. The PI or a delegate will inquire about adverse events at each follow-up visit. The PI will maintain
 records of all adverse events and will use the NCI Common Terminology Criteria for Adverse Events (CTCAE) for
 documentation. Additionally, a data and safety monitoring committee (DSMC) will be established and consist of the
 principal investigator and co-investigators. Adverse events will be reviewed at least bi- annually, or, more often if
 needed. To help capture data for adverse events in the discharged postoperative period, the participant will be given
 the contact information of the research coordinator at the time of consent in order to report any adverse events. The
 research coordinator will document the unexpected adverse events, or expected adverse events with higher than

 expected severity, and their resolution on a detailed log for the regulatory binder, on PDMS, and to the PI. Serious
 adverse events will be reported immediately to the IRB.
Suspension Reported to
Adverse events occurring during the study will be reported to the Mount Sinai Program for the Protection of Human
 Subjects (PPHS). Any suspension of the study will be reported to the PI and PPHS. 
Anticipated Circumstances of Subject Withdrawal
Previously enrolled subjects who do not meet inclusion criteria due to an an intraoperative decision will be removed
 from the study. For instance, if an initially planned free tissue transfer reconstruction is forgone for a local-regional
 flap reconstruction the subject will no longer meet criteria for inclusion into the study. Once patients are withdrawn, a
 record of the signed consent form along with the reason for withdrawal will be stored and filed. Enrolled patients who
 fail to have a successful placement of donor site catheter will be withdrawn from the study.
Primary or Secondary Safety Endpoints
Median postoperative pain score on the visual analogue scale (VAS), recorded over the 48 hours. Secondary Study
 Endpoints: total opiate consumption, achievement of physical therapy milestones, patient satisfaction, and side
 effects of opiates (nausea/vomiting, pruritus) Primary Safety Endpoints: Infection at the site of local infusion catheter,
 donor site hematoma, seroma, wound dehiscence, compartment syndrome, and ropivacaine toxicity or allergy
Data Monitoring Committee
 Description
DSMC Description.docx
DMC Charter Available
No
Will the Research Include Data
 Coordinating Center Activities?
No
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IRB-17-01893
Amendment
Brett Miles
19. Drugs / Biologics
Study Fund Account (or alternate
 departmental / fund account, if
 study is not yet established)
0244-4460
Select One:
Alternate or Temporary Fund (e.g.
 Departmental Fund)
  A fund number is required before the IDS will sign off on any forms or initiate any
 procedures. For those studies which an alternate departmental fund number is provided,
 IDS will delay billing by 6 months.
  
 
        Add all drugs and biological agents whose use is specifically prescribed in the
 research.  This includes approved drugs that are supplied or paid for by the company for
 this research, approved drugs that are not given under routine care guidelines, and all
 investigational drugs.  Approved drugs whose use is up to the discretion of an attending
 physician as part of medical care do not need to be added.  Contact the Investigational
 Drug Service (IDS) if unsure http://www.mssm.edu/ids .
  
 
            To be completed by Pharmacy staff upon review of the protocol:
   
   FYI: NO ACTION REQUIRED
   IDS FEE SCHEDULE
   Review:  ___
   Initiation:___
   Dispensation:___
   Maintenance:___
   Special Compounding:___
   Coordinating Center:___
   Close-Out:___
   
       
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IRB-17-01893
Amendment
Brett Miles
20. Financial Administration
  This information will help the Financial Administration of Clinical Trials Services (FACTS)
 office determine whether a Medicare Coverage Analysis (MCA) is needed for the research
 study. If you have any questions while completing this form, please contact the FACTS
 office at (212) 731-7067 or FACTS@mssm.edu.
  
 
Clinical Research Study Category
Investigator Initiated
  Payment Options: 
  * Option 1:  No protocol-required services will be billed to patients or third-party payers.
 Does Not Need MCA 
  * Option 2:  Protocol-required services (i.e., routine care services) will be billed to patients
 or third-party payers. Must Have MCA 
  * Option 3:  Study is initiated and federally funded by a Government Sponsored
 Cooperative Group who will only pay for services that are solely conducted for research
 purposes and other protocol-required services (i.e., routine care services) will be billed to
 patients or third-party payers. Billing Grid Only Required, NO MCA 
  * Option 4:  Study involves only data collection and has no protocol-required clinical
 services. Does Not Need MCA 
  * Option 5:  Study is not described in any of the above options. Please describe the study
 and specify whether External Sponsor (i.e., industry, government, or philanthropic source)
 and/or patient/third party payer will pay for protocol required services. MCA MAY Be
 Required 
  
 
Payment Option
Option 1
  
  No MCA is needed per option selected above. 
  
 
  
  Payment Option 1: 
  * Option 1A:  Department/collaborating departments will act as internal sponsor paying for
 all protocol-required services and no protocol-required services will be billed to patients or
 third party payers. 
  * Option 1B:  Study involves protocol-required clinical services and an External Sponsor
 (i.e., industry, government, or philanthropic source) will pay for all protocol-required
 services. 
  
 
Payment Option 1
Option 1A
Page 28 of 29

IRB-17-01893
Amendment
Brett Miles
21. Attachments
Type
Name
Version Status
Filename
Uploaded
 Date
Other - Non-
valadated Surveys/
Interview Documents
APS-Patient
 Outcome
 Questionnaire (APS-
POQ-R)
1
approvedAPS-POQ-R Pain
 Survey.pdf
05/06/2017
Data Monitoring
 Committee
 Description
DSMC
 Description.docx
1
approvedDSMC
 Description.docx
06/08/2017
Other - Non-
valadated Surveys/
Interview Documents
VAS pain scale
 sample/example
1
approvedVisual Analogue
 Scale Sample.png
06/08/2017
Package Insert
 Document (DRUG
 NAME)
Ropivacaine-
Naropin Package
 Insert020533s020s021lbl.pdf
1
approvedRopivacaine-
Naropin Package
 Insert020533s020s021lbl.pdf
07/05/2017
Other - Other IRB
 Correspondance
Ideate Spanish
 Consent Form
 Attestation
1
approvedLLS Agency
 Certification.pdf
09/12/2017
Other - Other IRB
 Correspondance
DSMC Meeting
 Minutes
1
approvedDSMC Meeting
 minutes
 12.1.17.docx
05/30/2018
Other - Other IRB
 Correspondance
DSMC Meeting
 Minutes
1
approvedDSMC Meeting
 minutes 5.4.18.docx
05/30/2018
Other - Other IRB
 Correspondance
Signed Attestation
1
approvedFind Attestation.pdf
07/27/2018
Consent - Consent
 Document
Ideate 502a Consent
 Form English
1
New
Ideate HRP 502-
Clean Role of
 Ropivacaine English
 09.05.2018.doc
09/19/2018
Consent - Consent
 Document
Ideate 502 Consent
 Form Spanish
1
New
Ideate HRP 502-
Clean Role of
 Ropivacaine Spanish
 09.05.2018 ....docx
09/19/2018
 
Page 29 of 29