Clinical trial NCT02688530
Conditions: Shoulder Arthroscopy Pain
Sponsor: Hospital for Special Surgery, New York
Start date: 2016-05-01; Completion date: 2017-11-19
Enrollment: 140 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Previous studies have confirmed that IV dexamethasone prolongs brachial plexus blocks. However, these studies only used fixed doses of IV dexamethasone at relatively high doses, which could potentially lead to increased glucose levels, delayed wound healing, and unintended side effects. There remains a paucity of research on the effective dose range of IV dexamethasone for the prolongation of supraclavicular blocks. The optimal dosage of IV dexamethasone for prolongation of analgesia vs. motor block prolongation from supraclavicular blocks in shoulder surgery has yet to be delineated.

Detailed description:
Numerous studies have confirmed that perineural dexamethasone prolongs bupivacaine and ropivacaine brachial plexus blocks by approximately 10 hours (from approx. 12 to 22 hours) without clinical evidence of toxicity. However, perineural toxicity in an animal model has raised concern about its use as a peripheral nerve block adjuvant. Moreover, recent studies suggest that high dose IV dexamethasone (810mg) prolongs analgesia to a similar degree as perineural dexamethasone for interscalene, supraclavicular and sciatic nerve blocks performed with ropivacaine and bupivacaine. However these studies only utilized fixed, high level doses of IV dexamethasone. Moreover, there remains a concern that high dose IV dexamethasone may lead to postoperative hyperglycemia and could possibly increase the risk of postoperative wound infection. Open surgery under general anesthesia has been shown to increase blood glucose levels with a peak at approximately 2 hours post-induction and results have been conflicting regarding whether or not IV dexamethasone causes greater increase. To the investigators' knowledge, it is not yet known if arthroscopic surgery under regional anesthesia triggers a similar increase in blood glucose levels and if this is impacted by administration of IV dexamethasone. The investigators aim to identify the duration of supraclavicular block prolongation that can be expected over a range of doses of IV dexamethasone. The investigators also seek to identify what association, if any, is noted between IV dexamethasone and changes in blood glucose levels after shoulder surgery with regional anesthesia and sedation. Finally, the investigators will collect data on side effects and postoperative complications, if any, in patients receiving a range of doses of IV dexamethasone.

Arms: arm 1: 0mg IV Dexamethasone arm 2: 4mg IV Dexamethasone arm 3: 6mg IV Dexamethasone arm 4: 8mg IV Dexamethasone
Interventions: intervention 1: IV Saline intervention 2: IV Dexamethasone 4mg intervention 3: IV Dexamethasone 6mg intervention 4: IV Dexamethasone 8mg
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_SAP_000.pdf: 
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Intravenous Dexamethasone for Prolongation of Analgesia Following 
Supraclavicular Brachial Plexus Block for Shoulder Arthroscopy: A Randomized, 
Controlled, Phase IV Dose Response 
 
FUNDER: Anesthesia Research Fund 
PROTOCOL NO.: 2015-853 
VERSION & DATE: 9/29/2016 
 
 
 
 
 
 
 
 
 
 
 
 
This document contains the confidential information of the Hospital for Special Surgery.  It is provided to you and your company’s personnel for 
review.  Your acceptance of this document constitutes an agreement that you will not disclose the information contained herein to others without 
the prior written consent of the Hospital for Special Surgery.  No other use or reproduction is authorized by Hospital for Special Surgery, nor does 
the Hospital for Special Surgery assume any responsibility for unauthorized use of this protocol. 
 


 
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TABLE OF CONTENTS 
TABLE OF CONTENTS................................................................................................................... 2 
PROTOCOL SYNOPSIS ................................................................................................................. 3 
1.0     INTRODUCTION .................................................................................................................... 4 
    2.0 
PRODUCT DESCRIPTION………………………..……………………………………………….4 
3.0      OBJECTIVE OF CLINICAL STUDY ...................................................................................... 4 
4.0      STUDY HYPOTHESIS ........................................................................................................... 4 
5.0      STUDY DESIGN .................................................................................................................... 4 
5.1 
Study Duration ................................................................................................................ 4 
5.2 
Endpoints ....................................................................................................................... 4 
5.2.1 
Primary Endpoint ...................................................................................................... 4 
5.2.2 
Secondary Endpoints ................................................................................................ 4 
5.2.3 
Safety Evaluations. ................................................................................................... 4 
5.3 
Study Site ....................................................................................................................... 4 
6.0        STUDY POPULATION ......................................................................................................... 4 
6.1 
Number of Subjects ........................................................................................................ 4 
6.2 
Inclusion Criteria ............................................................................................................. 5 
6.3 
Exclusion Criteria: .......................................................................................................... 5 
    6.4        Randomization………………………………………………………………………………..5 
7.0         PROCEDURES .................................................................................................................... 5 
7.1 
Surgical Procedure ......................................................................................................... 5 
 
7.1.1. Investigational Product Administration………………………………………………. .…..5 
7.2 
Imaging Procedure ......................................................................................................... 5 
7.3 
Medical Record Requirements ....................................................................................... 5 
7.4 
Data Collection ............................................................................................................... 5 
    7.5        Schedule of Assessments……………………………………………………..…………….. 6 
7.6 
Radiological Evaluations ................................................................................................ 7 
7.7 
Clinical Evaluations ........................................................................................................ 7 
 
7.7.1. Revision Surgery………………………………………………………………………. .……7 
8.0         STATISTICAL ANALYSIS .................................................................................................. 7 
9.0         ADVERSE EVENT ASSESSMENT ..................................................................................... 7 
9.1 
Adverse Event (AE) ........................................................................................................ 7 
9.2 
Serious Adverse Events (SAE) ...................................................................................... 7 
9.3 
Subsequent Surgical Interventions Definitions .............................................................. 7 
9.4 
Adverse Event Relationship ........................................................................................... 7 
9.5 
Adverse Event Recording .............................................................................................. 7 
9.6 
Adverse Event Reporting ............................................................................................... 7 
10.0         INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS ................................ 7 
10.1 
Subject Consent and Information ................................................................................... 7 
10.2 
Subject Data Protection ................................................................................................. 7 
10.3 
Staff Information ............................................................................................................. 8 
10.4 
Protocol Reviews ............................................................................................................ 8 
10.5 
Investigator Records ...................................................................................................... 8 
10.6 
Investigator Reports ....................................................................................................... 8 


 
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 11.0  
REFERENCES……………………………………………………………….………………….8 
APPENDIX A: Case Report Forms .............................................................................................. 9 
 
PROTOCOL SYNOPSIS 
Protocol Title: 
Intravenous Dexamethasone for Prolongation of Analgesia Following 
Supraclavicular Brachial Plexus Block for Shoulder Arthroscopy: A 
Randomized, Controlled, Phase IV Dose Response Study 
Protocol Number: 
2015-853 
Protocol Date: 
9/29/2016 
Sponsor: 
Anesthesia Research Fund 
Principal Investigator: 
Meghan Kirksey 
Products: 
IV Dexamethasone (Fresenius Kabi USA, LLC) 
Objective: 
The study is looking for findings that may allow clinicians to use lower 
doses of IV dexamethasone to maximize improve patient satisfaction, 
and minimize side effects. 
Study Design: 
Randomized Control Trial  
Enrollment: 
140 
Subject Criteria: 
1. Patients undergoing shoulder arthroscopy under regional 
anesthesia 
2. Ages 18-80 
Study Duration: 
• 
5/23/16-10/20/2017 
Data Collection: 
Name, ID, age, ethnicity, race, gender, height, weight, BMI, ASA, 
time of IV Dexamethasone administration, block injection time, 
Midazolam dose, Midazolam time administration, Fentanyl time 
administration, Fentanyl dose, deviation from protocol, fingerstick 
blood glucose, NRS Score, NRS (average, worst, best), hand 
grip, motor exam, sensory exam, time of motor block resolution 
wrist, motor block resolution elbow, pain relief from block, time to 
first pain, time of normal sensation, total daily amount of opioid 
taken, total daily amount of antiemetic taken, nausea, vomiting, 
pruritis, satisfaction with post op analgesia, Postop complications 
nerve injury, wound healing, infection, reason for dissatisfaction 
with postop analgesia, dose of IV dexamethasone. 
Outcome Parameters: 
Duration of motor block from the supraclavicular block will be defined as 
the time from block placement to restoration of normal strength at both 
the wrist and elbow. Strength will be assessed before discharge from 
PACU, on POD#1 and POD#2, and on POD#3 (if the block persists). A 
hand grip strength test will also be performed preoperatively 
in the holding area and postoperatively in the PACU. 


 
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Blood glucose levels, which will be checked by fingerstick (1) in the 
operating room after sedation and prior to nerve block and IV 
dexamethasone, (2) in the OR or PACU 1 hour after administration of 
dexamethasone, and (3) in the OR or PACU 2 hours after administration 
of dexamethasone.  
Statistical Analysis: 
Dunnett’s test (three pairwise comparisons, one between 
each of the three IV dexamethasone groups and control) 
 
 
 


 
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1.0 INTRODUCTION: 
In order to determine the effects of IV dexamethasone on block duration and blood glucose 
levels, it is necessary to know the duration of such blocks in the absence of IV dexamethasone and 
the impact of surgery and anesthesia on blood glucose in the absence of IV dexamethasone. Should 
any patient develop postoperative nausea refractory to zofran, other standard antiemetics can be 
administered, such as scopolamine, Trimethobenzamide, and reglan. IV dexamethasone can be 
administered for nausea in the PACU at the discretion of the prescriber, however this will be 
considered a deviation from protocol and data from these patients will be analyzed as part of an 
intention to treat analysis. 
2.0 PRODUCT DESCRIPTION:  
Numerous studies have confirmed that perineural dexamethasone prolongs 
bupivacaine and ropivacaine brachial plexus blocks by approximately 10 hours 
(from approx. 12 to 22 hours)(1) without clinical evidence of toxicity. However, perineural toxicity in an 
animal model has raised concern about its use as a peripheral nerve block adjuvant (2). Moreover, 
recent studies suggest that high dose IV dexamethasone (810mg) prolongs analgesia to a similar 
degree as perineural dexamethasone for interscalene (3), supraclavicular (4) and sciatic nerve (5) 
blocks performed with ropivacaine and bupivacaine. However these studies only utilized fixed, high 
level doses of IV dexamethasone. Moreover, there remains a concern that high dose IV 
dexamethasone may lead to postoperative hyperglycemia and could possibly increase the risk of 
postoperative wound infection (6,8). Open surgery under general anesthesia has been shown to 
increase blood glucose levels with a peak at approximately 2 hours postinduction and results have 
been conflicting regarding whether or not IV dexamethasone causes greater increase (9,10). To our 
knowledge, it is not yet known if arthroscopic surgery under regional anesthesia triggers a similar 
increase in blood glucose levels and if this is impacted by administration of IV dexamethasone. 
3.0 OBJECTIVE OF CLINICAL STUDY 
A supraclavicular nerve block is an injection of numbing medication (local anesthetic) near nerves 
that supply your shoulder that is often used to provide numbness both during and after surgery. The 
purpose of this study is to determine the effect of a medication called dexamethasone on the duration 
of the supraclavicular nerve block that you will receive for your surgery today. Advantages of 
prolonging the duration of a nerve block include lower pain levels  
and less of a need to use pain-killers, postoperatively.  
4.0 STUDY HYPOTHESES 
IV dexamethasone prolongs analgesia after supraclavicular nerve blocks 
performed for shoulder arthroscopy and the effect is dose dependent. 
5.0 STUDY DESIGN 
This is the “gold standard” for clinical research. These prospective 
studies have at least two groups. Patients meeting strict 
inclusion/exclusion criteria are enrolled and randomly assigned to 
receive either an experimental intervention or to receive what is 
considered to be an acceptable alternative – usually the current 
standard of care or a placebo (e.g., study of hylauronic acid injection 
versus cortisone for arthritis). 


 
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5.1 
Study Duration 
There will be follow ups for the following days:  
POD0, POD1, POD2, POD3, POD 21. 
5.2 
Endpoints 
 
5.2.1 
Primary Endpoint 
• 
Participation will involve, at most, 5 study contacts – which will include one 
preoperative contact and up to four following surgery. Follow up will be by phone on 
the first and second day after surgery to ask questions about pain, sensation, use of 
pain medication, and any problems after surgery.  If there are still numb from the 
block on the second day after surgery (this is unlikely), we will follow up with a call on 
the third day.   
Secondary Endpoints 
• 
Three weeks after surgery (day 21), we will place a call for a final time to ask about 
subject’s experience and satisfaction with subject’s care. Each contact is expected to 
average about 15 minutes. 
5.2.2 
Safety Evaluations: 
• 
Glucose test, surveys/questionnaires, randomization, surgery. 
5.3 
Study Sites 
The study will be performed at the main hospital. 
6.0 STUDY POPULATION 
6.1 
Number of Subjects 
140 
6.2 
Inclusion Criteria 
Subjects of either gender will be included if they: 
1. Patients undergoing shoulder arthroscopy under regional anesthesia 
2. Ages 18-80 
6.3 
Exclusion Criteria 
Subjects will be excluded from the study if they: 
1. General anesthesia 
2. Contraindication to regional anesthesia 
3. Pre-existing neuropathy in the surgical limb 
4. Intraarticular injections for postoperative pain control 
5. Diabetes Mellitus 
6. History of postoperative nausea and vomiting and/or motion sickness 
7. Open surgical procedures 
8. Patients on systemic oral or IV steroid therapy within 6 months 
9. Patients who received Cortisone injection(s) within 1 month 


 
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10. Chronic opioid usage (defined as daily opioid and/or gabapentinoid consumption for 
6 weeks) 
11. Non English speaking 
 
6.4 
Randomization 
 Randomizer an Excel compatible randomizing program will be used by non-study research 
personnel to assign the dose of IV dexamethasone that will be administered for each study 
case. The designated dose of IV dexamethasone (either 0mg, 4mg, 6mg, or 8mg) will be 
prepared by someone other than the anesthesia provider within a blinded syringe. 
  
PROCEDURES 
6.5 
Surgical Procedure 
           Shoulder arthroscopy 
6.5.1 
Investigational Product Application 
           N/A 
6.6 
Imaging Procedure 
         N/A 
6.7 
 Medical Record Requirements 
          N/A 
6.8 
Data Collection 
The following data will be collected: 
 
Pre-operative/Baseline 
• 
basic demographic data 
• 
patient weight & height, BMI 
 
Surgical procedure 
• 
date of surgery 
• 
type of surgery 
 
Follow-up visits (6 weeks, 12 weeks, 6 months, 1 year, 2 years) 
• 
There will be no extra visits. A phone call will be performed on POD21.  


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6.9 
Schedule of Assessments 
STUDY VISIT # 
FINGER STICK 
BLOOD 
GLUCOSE TEST 
SURVEYS / QUESTIONNAIRES 
RANDOMIZATION 
SURGERY 
#1: Holding Area 
(Before Surgery) 
 
X 
X 
SOC 
#2: Operating 
Room (During 
Surgery) 
X 
 
 
 
#3: Recovery Room 
X 
X 
 
 
#4: Postoperative 
Day 1 
 
X (via phone) 
 
 
#5: Postoperative 
Day 2 
 
X (via phone) 
 
 
#6: Postoperative 
Day 3 (if necessary) 
 
X (via phone) 
 
 
#7: Postoperative 
Day 21  
 
X (via phone) 
 
 
 


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6.10 Radiological Evaluations 
         N/A 
6.11 Clinical Evaluations 
N/A 
6.11.1 Revision Surgery 
N/A 
7.0 STATISTICAL ANALYSIS 
1. Proposed analysis (e.g., student’s t-test, ANOVA, chi square, 
regression, etc.): Dunnett’s test (three pairwise comparisons, one between 
each of the three IV dexamethasone groups and control) 
2. Alpha level: Family wise type I error rate = 0.05 (two sided) 
3. Beta or power level: 80% power to detect all pairs of groups that actually differ in duration of 
analgesia 
4. Primary outcome variable estimate (mean +/s.d. for continuous outcome, frequency/percentage for 
categorical variable): Mean ± SD duration of analgesia in control group = 13.7 ± 8.5 hours (Desmet 
2013) 
5. Number of groups being compared (use 1 for paired analysis within the same subjects): 4 
6. Effect size or change expected between groups: Investigators defined 8 hours as a clinically 
meaningful difference in duration of analgesia 
7. Resulting number per group: 31 
8. Total sample size required: 124 + 10% to account for attrition = 138 (round up to 140) 
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report. Definitions for Adverse 
Event (AE) used in this study are listed below and are based on FDA and international 
guidelines: 
 
8.1 
Adverse Event (AE) 
 
8.2 
Serious Adverse Events (SAE) 
 
8.3 
Subsequent Surgical Interventions Definitions 
 
8.4 
Adverse Event Relationship 
Participation in this research involves the potential risk of a breach of confidentiality to your 
stored health information.  HSS tries to minimize those risks by (i) removing some direct 
identifiers from stored information (i.e., names, social security numbers, medical record 
numbers); (ii) securing, in a separate location, and limiting access to information that would 
identify you; and (iii) limiting access to information stored to HSS investigators. 
 


 
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There may be risks or side effects that are unknown at this time. If we learn about new risks that may 
affect your willingness to continue your participation, we will make you aware of them and you will be 
asked to re-consent to continue your participate in the study. 
 
 
 
8.5 
Adverse Event Recording 
 
8.6 
Adverse Event Reporting 
 
9.0 INVESTIGATOR RESPONSIBILITIES, RECORD AND REPORTS 
 
9.1 
Subject Consent and Information 
Patients will be identified from the OR schedule on the day before surgery. On the day of surgery, the 
RA or anesthesiologists will approach and consent eligible patients in the holding area. 
9.2 
Subject Data Protection 
Any information collected electronically will be stored on the REDCap server. The REDCap server 
and data are hosted by Weill Cornell Medical College CTSC, with the servers physically located in the 
Payson building of Weill Cornell New York Presbyterian Hospital. Access to this space is limited to 
members of the Hospital’s informatics department. Electronically, several intrusion protection 
mechanisms, including firewalls and encryption, are in place to protect the server and its data. Any 
paper based data sheets utilized for the study will be stripped of all personal identifiers whenever 
possible and stored the department’s locked office. 
9.3 
Staff Information 
Eugene Kremer 
Meghan Kirksey, MD, Ph.D. 
Jacques YaDeau, MD, PhD IRB Vice Chair 
Carrie Guheen, MD 
Angie Zhang, Research Assistant 
Stephen Caleb Haskins, MD  
Isabel Armendi, Research Assistant 
Thuyvan Luu, Research Assistant 
Swetha Pakala, MD 
Ajay Dharmappa, MD 
Jodie Curren, RN 
Candace Gopaul 
Denesy Mancenido  
Mark Jensen 
Pamela Wendel, MD 
Aaron Schweitzer, Research Assistant 
Jennifer Cheng Research Associate 
Valeria Buschiazzo 
Phuong Dinh Mac, Research Assistant 
Kanupriya Kumar, M.D. 
Katherine Lee, Research Assistant 


 
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Richard Kahn, MD 
 
9.4 
Protocol Reviews 
Literature searches will be conducted on a routine basis to search for latest news 
concerning dexamethasone and patient safety. If the drug is deemed unsafe at 
any point, or if significant development arise, immediate changes will be made to 
the study protocol and informed consent form. 
 
10.0 REFERENCES 
1. Choi S, Rodseth R, McCartney CJ (2014) Effects of dexamethasone as a local anaesthetic 
adjuvant for brachial plexus block: a systematic review and meta-analysis of randomized trials. Br J 
Anaesth 112: 427439. 
2. Williams BA, Hough KA, Tsui BY, et al. (2011) Neurotoxicity of adjuvant used in perineural 
anesthesia and analgesia in comparison with ropivicaine. Regional anesthesia and pain medicine 36: 
225230. 
3. Desmet M, Braems H, Reynvoet M, Plasschaert S, Van Cauwelaert J, et al. (2013) I.V. and 
perineural dexamethasone are equivalent in increasing the analgesic duration of a single shot 
interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo 
controlled study. Br J Anaesth 111: 445452. 
4. Abdallah FW, Johnson J, Chan V, Murgatroyd H, Ghafari M, Ami N, Jin R, Brull R. (2015) 
Intravenous dexamethasone and perineural dexamethasone similarly prolong the duration of 
analgesia after supraclavicular brachial plexus block: a randomized, triple arm, double blind, 
Placebo controlled trial. Regional anesthesia and pain medicine. MarApr;40(2):12532. 
5. Rahangdale R, Kendall MC, McCarthy RJ, Tureanu L, Doty R, Jr., et al. (2014) The effects of 
perineural versus intravenous dexamethasone on sciatic nerve blockade outcomes: a randomized, 
double blind, placebo controlled study. Anesth Analg 118: 11131119. 
6. Dhatariya K. (2013) Does dexamethasone induced hyperglycemia contribute to postoperative 
morbidity and mortality? British journal of Anaesthesia. 110 (5): 674675. 
7. Pasternak, Jeffrey J, McGregor, Diana G.; Lanier, William L. (2004) Effect of Single Dose 
Dexamethasone on Blood Glucose Concentration in Patients Undergoing Craniotomy. Journal of 
Neurosurgical Anesthesiology. 16(2):122125. 
8. Short TG, Leslie K. Dexamethasone an effective antiemetic, but is it safe? 
(2015). Anaesth Intensive Care 2015 43 (2): 155156. 
9. Abdelmalak BB1, Bonilla AM, Yang D, Chowdary HT, Gottlieb A, Lyden SP, 
Sessler DI. (2013). The hyperglycemic response to major noncardiac surgery and the added effect of 
steroid administration in patients with and without diabetes. Anesth Analg. 2013 May;116(5):111622. 
10. Murphy GS1, Szokol JW, Avram MJ, Greenberg SB, Shear T, Vender JS, Gray J, Landry E. The 
effect of single low dose dexamethasone on blood glucose concentrations in the perioperative period: 
a randomized, placebo controlled investigation in gynecologic surgical patients. Anesth Analg. 2014 
Jun;118(6):120412.