Clinical trial NCT03679013
Conditions: Pain, Postoperative
Keywords: cardiac surgery pain
Sponsor: Inova Health Care Services
Start date: 2019-04-19; Completion date: 2019-07-12
Enrollment: 19 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The Inova Heart and Vascular Institute (IHVI) perform over 300 coronary artery bypass graft (CABG) surgeries per year. While opioid medications are the institutional standard of care for post-operative pain therapy little is known about the variation in pain scores, incidence of post- operative complications, and cost of hospitalization when an alternative multimodal pain regimen consisting of oral Gabapentin and intravenous Acetaminophen (IV APAP) is utilized.

The objective is to determine whether there is a substantial difference in pain scores, incidence of post-operative complications, and costs associated with hospitalization when a non-opioid multimodal pain regimen is utilized A single- center, open label, prospective, randomized, controlled clinical trial comprised of 20 total patients who have undergone isolated CABG at the IHVI will be conducted. Separate cohorts will include patients receiving opioid medications post-operatively (Group 1) and patients receiving the non-opioid regimen of oral Gabapentin and IV APAP (Group 2) to be followed for 72 hours post CABG surgery.

Main outcome measures include pain scores in both study groups, requests for breakthrough pain medication in both groups, gastrointestinal and respiratory complications of ileus and reduction in tidal volumes or forced vital capacity (FVC) at baseline and at 72 hours,increase in serum AST/ALT, and comparison of cost of hospitalization between groups.

The objective of this pilot study is to provide evidence that multimodal pain therapy utilizing IV APAP and PO Gabapentin will provide more effective pain relief than standard of care opioids as evidenced by pain scores \<2. And the reduced consumption of opioids will lead to a reduction in ileus, no increase in AST/ALT, post-operative tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, while also showing a positive effect on the cost of hospitalization.

Detailed description:
The Cardiovascular Intensive Care Unit (CVICU) of the Inova Heart and Vascular Institute (IHVI) will be the setting of this clinical trial involving two groups of subjects and comparing the opiate based standard of care regimen currently adopted (Group 1) at the IHVI with a treatment group (Group 2). Group 2 will receive a scheduled multimodal pain regimen consisting of PO (pro ora \[oral\]) Gabapentin paired with intravenous Acetaminophen. Opioids will be available for breakthrough pain in the treatment group for pain scores greater than 4. The outcomes of total opioid consumption and minimum/ maximum pain scores will be assessed at the 24 hours, 48 hours, 72 hours, and PRN (pro re nata \[as the situation demands\]) timepoints. Assessment will include amount of opioids consumed in both groups as well as number of requests for breakthrough pain medication in Group 2.

Minimum and maximum pain scores in all study groups will be assessed via Numeric Rating Scale (0-10) as per Inova Health System (IHS) policy; 'Pain Management for the Adult Population', at 24 hours, 48 hours, 72 hours, and PRN with opioid requests in all groups and opioid administration follow up within one hour as per IHS inpatient medication administration policy. Follow up medication administration scores will not be recorded as part of study results.

Secondary assessments will include the incidence of ileus both during hospitalization, increase in aspartate aminotransferase (AST)/ alanine aminotransferase (ALT), post-operative tidal volumes as assessed by incentive spirometry as compared to pre- surgical values, time from Cardiovascular Intensive Care Unit (CVICU) arrival to extubation in both groups, and the effects of an opioid based regimen versus an opioid sparing regimen on cost of medication and hospitalization.

The investigators hypothesize that a scheduled opioid- sparing pain regimen consisting of intravenous Acetaminophen IV APAP and PO Gabapentin for 48 hours post- operatively will reduce opioid consumption while maintaining adequate pain relief as evidenced by pain scores less than two (2), and a reduction in opioid consumption, and that reduced opioid consumption will lead to a reduction in the incidence of ileus, an opioid related side effect, no increase in AST/ALT, post-operative tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, and demonstrate a positive effect on the cost of medication and hospitalization.

Arms: arm 1: Inova Heart and Vascular Institute (IHVI) opioid based standard of care regimen given for post operative cardiac surgery pain. arm 2: Multimodal pain regimen consisting of PO Gabapentin paired with intravenous Acetaminophen given for post operative cardiac surgery pain.
Interventions: intervention 1: Oral Gabapentin and Intravenous Acetaminophen (IV APAP) intervention 2: Opiate based pain regimen.
Intervention descriptions: intervention 1: Scheduled multimodal pain regimen consisting of oral Gabapentin paired with intravenous Acetaminophen following cardiopulmonary bypass surgery. intervention 2: Standard of care opiate based pain regimen.

Protocol documents:
Prot_SAP_000.pdf: 
Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 1 of 13  
 
 
 
 
 
A Pilot Study Comparing the Effectiveness of an Opioid- Sparing Analgesic Regimen and an Opioid 
Based Regimen on Post- Operative Pain Control in Cardiac Surgery Patients (INOVA OPIOID) 
 
 
 
 
 
 
 
 
 
Principal Investigator: Ramesh Singh MD 
 
 
Sub-Investigator: Eric L. Sarin MD 
 
 
Site of Investigation: Inova Heart and Vascular Institute 
Falls Church, Virginia 
 
 
December 10, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
_______________________________________________________________________________________________ 
 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 2 of 13  
 
ABSTRACT 
 
  
Title:   
 
 
A Pilot Study Comparing the Effectiveness of Opioid- Sparing Analgesic Regimen and an  
 
 
 
Opioid Based Regimen on Post- Operative Pain Control in Cardiac Surgery Patients 
 
Short Title:    
 
Opioid Sparing in Post-Operative Cardiac Surgery Pain (INOVA OPIOID) 
 
Rationale:      
 
To demonstrate the effectiveness of an opioid sparing pain regimen post cardiac  
 
 
 
 
surgery to provide optimal pain relief as well as to minimize opioid related side  
 
 
 
 
effects.  
 
Objectives:     
 
We hypothesize that an opioid- sparing regimen consisting of scheduled   
 
 
 
 
acetaminophen and gabapentin for 72 hours post- operatively, will reduce  
 
 
 
 
opioid consumption, reduce opioid related side effects, and result in a decrease in   
 
 
 
overall healthcare costs.  
 
Study Type:   
 
Single center, open label, prospective, randomized clinical trial. 
 
Study Design:   
 
A total of 20 patients between the ages of 18-85 years old that have undergone  
 
 
 
 
sternotomy procedures in the context of cardiac surgery will be   
 
 
 
 
 
randomized to one of two treatment groups. 
 
Study Methodology:   
We will analyze the total opioid consumption and pain scores of sternotomy patients beginning 
 
 
 
with admission to CVICU post-surgery (day 0) through post-operative day three (day 3) in  
 
 
 
patients  receiving acetaminophen IV paired with gabapentin pro ora (PO).  
 
 
 
 
Also analyzed will be hospital length of stay, incidence of ALT/AST >3X ULN (AST >168, 
 
 
 
ALT >105), occurrence of  ileus during hospitalization, pre and post-surgical  
 
 
                     incentive spirometry tidal volume values; pre  surgery and through post- operative day three (3), 
 
 
 
number of  hours post CVICU arrival to extubation and perform cost analysis assessment of  
 
 
 
medication and hospitalization costs.  
 
Statistical Methodology:  Although underpowered for this pilot, our statistical analysis plan is designed to similarly 
assess the feasibility of the larger study to follow. Primary analyses for this pilot will be to 
determine feasibility of larger study and determine estimates of primary outcome (e.g., total 
opioid consumption, pain scores, etc.) mean and variance parameters for sample size 
calculation. Estimates for study attrition, and secondary outcomes of hospital length of stay, 
incidence of AST/ALT > 3x ULN (AST >168, ALT >105), etc. will be calculated. All 
analyses will be conducted as intent-to-treat.  
 
 
 
 
 
 
 
               
 
 
 
 
 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 3 of 13  
 
  
1. 
INTRODUCTION 
 
 
1.1. 
Specific Aims 
 
The management of post-operative cardiac surgery pain representative of many etiologies remains a challenge 
to clinicians. Opioid pain medications can cause or exacerbate side effects which directly contribute to 
morbidity and mortality in post- operative cardiac surgery patients, as well as cost of medication and 
hospitalization. In this study we will demonstrate that an opioid sparing, multimodal pain regimen consisting of 
intravenous acetaminophen paired with PO gabapentin will reduce opioid consumption in addition to providing 
optimal pain relief, reduce opioid related side effects, and decrease the cost of medication and hospitalization. 
Reduction in opioid consumption and pain relief will be demonstrated by decreased patient self-report of pain 
and requests for breakthrough opioid pain medication. Reduction of opioid related side effects will be 
demonstrated by lack of incidence of ileus during hospitalization, tidal volumes that return and are maintained 
at pre surgical levels through post- operative day 3, and decreased time to extubation from Cardiovascular 
Intensive Care Unit (CVICU) arrival. Increase in AST/ALT will be monitored as a safety assessment.  
Additionally, we will demonstrate a reduction in total cost of hospitalization via decreased length of stay, as 
well as decreased medication costs. 
 
1.2. 
Hypothesis  
We hypothesize that an opioid- sparing pain regimen consisting of scheduled IV acetaminophen and PO 
gabapentin for 72 hours post- operatively will reduce opioid consumption while maintaining adequate pain 
relief as evidenced by pain scores less than two (2), and minimal request for breakthrough opioid medication, 
and that reduced opioid consumption will lead to a reduction in the incidence of ileus, rapid return to pre-
surgical respiratory tidal volumes, and timely extubation, AST/ALT within normal limits, and demonstrate a 
positive effect on the cost of medication and hospitalization. 
 
1.3. 
Background and Significance  
Post-Operative Cardiac Surgery Pain 
The management of pain resultant from cardiac surgery necessitating a sternotomy is a challenging clinical 
quandary. Post cardiac surgery pain is associated with a variety of etiologies; sternotomy incision, retraction of 
the ribs and sternum with possible rib dislocation or fracture, pericardotomy, internal mammary and or 
saphenous vein harvesting, operative trauma to the parietal pleura, insertion of chest tubes, reactions to 
pacemaker wires, brachial plexus injury, insertion of mediastinal and pleural drains, and other body trauma 
occurring as a result of surgery 1, 2. Cardiac surgery patients may experience severe pain in post anesthesia 
recovery as well as upon transfer to the Cardiovascular Intensive Care Unit 3. Well controlled pain 
postoperatively is associated with positive physical and psychological outcomes. Well controlled pain 
facilitates early extubation, improves hemodynamics, improves myocardial oxygenation, improves hemostatic 
and immunologic modulation, decreases the incidence of ischemic events, maximizes chest expansion during 
respiration,  enables early ambulation 2,4,5 and is responsible for the ensuing positive clinical outcomes that are 
associated with early ambulation (eg. deep vein thrombosis prophylaxis). Optimal pain control is associated 
with lower rates of cardiovascular complications, pneumonia, and avoidance of hypercoagulability in the 
postoperative recovery period 3, 6. Equally, poorly controlled pain is responsible for elevated catecholamine 
levels which can progressively trigger myocardial ischemia, stroke, and bleeding complications 4, 25 post cardiac 
surgery. Cardiac surgery has the potential to disrupt the normal process of coagulation which could predispose 
a patient to thrombosis, this process may be attenuated by the increased physiologic benefit of adequate pain 
relief and its effect on increasing blood flow 6. 
 
The Use of Opioids for Pain Management and Their Myriad Side Effects  
Opioid analgesics have traditionally been the mainstay of treatment for postoperative cardiac surgery pain 
despite the myriad negative side effects of these medication regimens which constitute major barriers to their 
use 4, 7. These side effects are frequently dose dependent and exert a profound negative influence on patient 
recovery, early discharge, safety, and associated morbidity and mortality 1, 7. Perhaps the most significant 
effects involve the incidence of post-operative nausea and vomiting (PONV) and paralytic ileus 2, 8, 9, 10. 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 4 of 13  
 
Paralytic ileus [ileus] refers to a state of low or absent peristalsis which results in secretion accumulation in the 
gastrointestinal tract leading to symmetric abdominal distension and vomiting 11. Paralytic ileus is a significant 
contributor to mortality post cardiac surgery. Paralytic ileus etiology is multifactorial. Most commonly ileus 
results from a low gastrointestinal flow state during the perioperative period 12. Surgical stress may disrupt the 
natural arrangement of the bowel and thus impair the function of the gastrointestinal tract 10.  PONV rates post 
cardiac surgery can range from 42- 71% of cardiac surgery patient utilizing opioids for post- operative pain 9. 
PONV is associated with aspiration pneumonia, dehydration, electrolyte imbalances, which in turn may lead to 
or contribute to dysrhythmia, fluid overload, and uncontrolled pain secondary to absorption anomalies 9. PONV 
has a profound impact on a patient’s ability to participate in their recovery 1, 9  Other harmful effects of post- 
operative opioid consumption include; constipation, profound sedation, dizziness and confusion especially in 
elderly patients, suppression of gastrointestinal motility, and respiratory depression 1, 13. Also concerning is that 
severe acute pain post sternotomy is a significant predictor of chronic pain which is fraught with profound 
psychological, physical, and financial costs 3, 14, 15, including chronic incisional pain and the potential for post- 
operative opioid addiction16 which has of late reached epidemic proportions25. More than 2 million Americans 
suffer from substance abuse related to opioid consumption 25.Opioid induced hyperalgesia (OIH) is also a 
significant complication of an opioid based pain regimen. OIH is the direct sequlae of chronic opioid 
administration and results in patients developing a heightened sensitivity to pain 13.  Finally, scholarly evidence 
for the use of chronic opioids in the treatment of non-cancerous pain does not exist. In fact eminent pain 
societies recommend the use of opioid medications with “great restraint and caution” 3, 17,25. Indications for 
responsible, effective pain management favor a plan based on the individual’s unique history and condition, a 
multimodal regimen, and multidisciplinary collaboration 1, 3, 18. 
 
Multimodal Analgesia Regimens 
Multimodal pain regimens offer significantly better relief in post cardiac surgery patients 1. Selection of a 
multimodal approach for post cardiac surgery pain is advocated to reduce opioid requirements. These regimens 
should include regional anesthesia, non-narcotic medication, and additional complimentary regimens2. 
Multimodal analgesia is the mainstay of responsible comprehensive individualized pain management 13. 
Multimodal analgesia is the combination of different pharmacologic agents and routes of administration in 
order to produce analgesic effects along multiple pain pathways 13. The use of multimodal analgesia provides 
pain relief that is both potent and synergistic while minimizing possible adverse effects of the medication 13. 
Multimodal pain regimens combine agents to provide both central and peripheral analgesia 4. The use of a 
multimodal pain regimen as opposed to an opiate based regimen offers significantly better pain relief 1, 17.  
 
The Use of Gabapentin and Intravenous Acetaminophen 
Gabapentinoids are effective on centrally mediated pain pathways and thus successful in the treatment of 
neuropathic pain, they have demonstrated a reduction in acute pain and have beneficial effects on the 
development of chronic pain and pain scores post-surgery 13, 14, 19, 20, 21, 22,25. Gabapentin with its anti-
inflammatory properties offers relief superior to opiates or acetaminophen alone in cardiac surgery patients 1, 5, 
20, 21. High quality evidence confirms the effectiveness of a multimodal regimen which includes 
acetaminophen17 IV (IV APAP) is a powerful potential constituent of a multimodal pain management regimen 
post cardiac surgery. Without serious side effects and when used as recommended this medication is devoid of 
platelet, kidney, or gastrointestinal sequelae and therefore is beneficial to the cardiac surgery patient in a 
variety of ways. The intravenous route (IV APAP) ensures more efficient absorption and avoids the first- pass 
metabolism effect.  
 
Post- Operative Pain Assessment 
The Numeric Rating Scale is a one dimensional measurement of pain intensity in the adult patient. Various 
versions of this scale exist although the most commonly used version involves a 1-10 scale for scoring pain. 
Zero (0) represents no patient reported pain and 10 represents the patient reporting [the] “worst pain 
imaginable”. The scale is administered verbally and the patient translates their pain intensity to a number on the 
scale. Higher scores indicate extreme pain23, 24. 
 
 
 
Study Procedures 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 5 of 13  
 
 
The Cardiovascular Intensive Care Unit (CVICU) will be the setting for our clinical trial involving two groups 
of subjects and comparing the post cardiac surgery opiate based standard of care regimen in effect at the time of 
protocol development (Group 1) within the IHS/IHVI at the Inova Fairfax Medical Campus (IFMC)with a 
treatment group (Group 2). Group 2 will receive a scheduled multimodal pain regimen consisting of PO 
gabapentin paired with intravenous acetaminophen. Opiates will be available for breakthrough pain in the 
treatment group for pain scores greater than 4. The outcomes of total opioid consumption and minimum/ 
maximum pain scores will be assessed at the 24 hours, 48 hours, 72 hours, and PRN timepoints. Assessment 
will include amount of opioids consumed in both groups as well as number of requests for breakthrough pain 
medication in Group 2. 
 
The term ‘Standard of Care’ in this protocol will refer to the adapted regimen of opioid based pain relief 
prescribed at the time of protocol development at the IHS/IHVI/IFMC. 
 
Standard of Care regimens at the IHS/IFMC are revised regularly based on advances in evidence based 
practice, patient response, continuously evolving safety information, issuance of professional society practice 
guidelines, and physician recommendations.  
 
While the post cardiac surgery pain standard of care regimen currently differs from the regimen to be 
administered to the Group 1 subjects in this clinical trial there is no change to the risk benefit ratio and is 
addressed in this protocol to provide transparency of practice. Also, this study will contribute meaningful 
evidence for future modifications to the standard of care at the IHS/IHVI/IFMC. 
 
Minimum and maximum pain scores in all study groups will be assessed via Numeric Rating Scale (0-10) as 
per Inova Health System (IHS) policy; ‘Pain Management for the Adult Population’, at 24 hours, 48 hours, 72 
hours, and PRN with opioid requests in all groups and opioid administration follow up within one hour as per 
IHS inpatient medication administration policy. Follow up medication administration scores will not be 
recorded as part of study results. 
 
Secondary assessments will include the incidence of ileus both during hospitalization, increase in AST/ALT, 
post-operative tidal volumes as assessed by incentive spirometry as compared to pre- surgical values, time from 
CVICU arrival to extubation in both groups, and the effects of an opioid based regimen versus an opioid 
sparing regimen on cost of medication and hospitalization.  
 
We hypothesize that a scheduled opioid- sparing pain regimen consisting of IV APAP and PO gabapentin for 
48 hours post- operatively will reduce opioid consumption while maintaining adequate pain relief as evidenced 
by pain scores less than two (2), and a reduction in opioid consumption, and that reduced opioid consumption 
will lead to a reduction in the incidence of ileus, an opioid related side effect, no increase in AST/ALT, post-
operative tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, and 
demonstrate a positive effect on the cost of medication and hospitalization. 
 
1.4 Preliminary Studies 
The objective of this pilot study is to provide evidence that multimodal pain therapy utilizing IV APAP and PO 
Gabapentin will provide more effective pain relief than standard of care opioids as evidenced by pain scores <2. 
And the reduced consumption of opioids will lead to a reduction in ileus, no increase in AST/ALT, post-operative 
tidal volumes as assessed by incentive spirometry comparable to pre- surgical values, while also showing a 
positive effect on the cost of medication and hospitalization. 
 
The Principle Investigator Ramesh Singh is a cardiothoracic surgeon at the Inova Heart and Vascular Institute 
(IHVI) with over 25 years of experience and well qualified for the design and conduct of the study. Dr. Singh has 
performed over 177 cardiothoracic surgeries at the IHVI in 2017 alone.  
  
2. STUDY DESIGN AND SUBJECT SELECTION  
 
 
2.1 Study Type 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 6 of 13  
 
 
 
Single center, open label, prospective, randomized clinical trial. 
 
    
2.2 Setting/Location 
 
Inova Heart and Vascular Institute (IHVI) 
 
3300 Gallows Road 
 
Falls Church, Virginia 22042 
 
 
2.3 Duration of Study 
 
Consented and randomized subjects will participate for three (3) days starting at admission to CVICU 
 
(day 0). Biological specimens will not be collected for the purposes of this study. 
 
 
 
 
2.4 Number of Subjects  
       A total of 20 patients, 10 per study arm are expected to participate in this study. 
 
 2.5 Study Population 
 2.5.1 Gender of Subjects 
 
The study population is inclusive of both genders (male and female). 
 
2.5.2 Age of Subjects 
 
Subject enrollment will be comprised of subjects 18- 85 years of age.   
 
2.5.3 Racial and Ethnic Origin  
 
The study population will be inclusive of all racial and ethnic subgroups.  
 
2.5.4 Vulnerable Populations 
 
Children, pregnant women, institutionalized persons, and persons with decisional incapacity will not be 
 
enrolled in this study. 
 
 
2.6 Recruitment  
 
Patients will be recruited upon first contact with the cardiac surgery service either while inpatient pre- 
 
surgery or outpatient at the Cardiac and Thoracic Surgery Associates office located at 2921 Telestar 
 
Court, Falls Church, Virginia during the preoperative consult/ visit. Patients will not be consented 
 
less than 24 hours before surgery to provide adequate time for participation consideration. 
 
 
2.7 Inclusion Criteria 
  1. Patient between 18 and 85 years old. 
      2. Elective or urgent surgery requiring sternotomy approach 
 3. Subject is able to read and has signed and dated the informed consent document including              
      authorization permitting release of personal health information (PHI) approved by the Inova           
      Institutional Review Board (IRB). 
 
 
2.8 Exclusion Criteria 
 
       1. Patients lacking enteral access on post-operative day 0 
 
 
2. Inability to communicate 
 
 
3. Active chronic pain with opioid therapy 
 
 
4. Active chronic use of gabapentin or pregabaldin  
 
       5. Active substance abuse 
 
 
6. Current self- report of alcoholism 
 
 
7. End stage renal disease 
 
 
8. Active renal dialysis therapy 
 
 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 7 of 13  
 
3. STUDY METHODS AND PROCEDURES 
 
 
3.1 Schedule of Assessments 
 
Schedule of Assessments 
Group 1:Standard of Care 
Group 2: Total 485 hours 
PRN opiates per patients self- report of pain. Dosing based on patient 
pain score report. 
Scheduled post-op loading dose of IV acetaminophen  1000mg X 1 dose 
AND Gabapentin 600 mg PO X 1 dose upon arrival to the Cardiovascular 
Intensive Care Unit (CVICU) 
Pain will be assessed in standard of care group every 12 hours or twice 
per day for 72 hours by study personnel. 
Pain will be assessed in standard of care group every 12 hours or twice per 
day for 72 hours by study personnel. 
Assessment of tidal volume via incentive spirometry q day by study 
personnel. 
Assessment of tidal volume via incentive spirometry q day by study 
personnel. 
1-3 (Mild pain) 
Acetaminophen 650 mg PO q4 hours (Mild pain) 
PRN 
Scheduled Acetaminophen 1000 mg IV q61,4 X 42 Hours and PO Gabapentin 
300 mg2 q8 hours X 40 Hours then discontinue2 
Then: 
Acetaminophen 1000 mg PO q6 hours PRN for pain scores 4-10 (Moderate to 
severe)4 
 
 
Patients with moderate hepatic disease and/or severe renal impairment will 
receive Acetaminophen 1000 mg PO q 12 hours X 48 hours, then q12 hours 
PRN for pain scores  1- 10 (mild to severe) 
 
Patients with Creatinine clearance <30mL/min will receive 100 mg 
Gabapentin PO q8 hours X 40 hours2 
 
First line: 
 
4-6 (Moderate pain): Tramadol 50mg PO q4 PRN 
 
Second line3: If first line is ineffective X 2 doses 
 
4-6 (Moderate pain):   Oxycodone/acetaminophen 5/325 mg PO q4 
hours  
 
     PRN  
 
 
 
7-10 (Severe pain): Hydromorphone 0.25 mg IV q3 hours PRN 
                      
 
Administered in conjunction with an opioids for moderate to severe 
breakthrough pain (Scores 4-10) 
Schedule for breakthrough pain Group 2: 
1st line: Score 4-6 Tramadol 50 mg q4 PRN 
2nd line3: Score 4-6 Oxycodone 10 mg PO q4 hours PRN 
Severe pain Score 7-10: Hydromorphone 0.25 mg IV q3 hours PRN 
1 Start 6 hours post CVICU arrival loading dose 
2 Start 8 hours post CVICU arrival loading dose 
3 If first line ineffective X 2 doses 
4 Acetaminophen administrations will not exceed 4000 mg per 24 hour period. 
5 Experimental regimen will be administered to Group 2 for 48 hours. Pain assessment will be for 72 hours beginning at time of CVICU arrival.  
 
 
3.2 Randomization  
 
Allocation of study treatment will be performed via a web-based interactive randomization system, based 
 
on a computer-generated random sequence with a random block size.  
 
 
3.3 Endpoints/Outcomes Measurements 
3.3.1 Primary Outcomes. 
 
The primary outcome will be reported as total opioid consumption in Group 2.Total opioid 
 
consumption in Group 2 will be assessed at 24 hours, 48 hours, and 72 hours from the initial dose of IV 
 
acetaminophen and PO gabapentin received upon arrival in the CVICU.  Assessment will include 
 
amount of opioids consumed as well as number of requests for breakthrough opioid pain medication in 
 
Group 2. 
 
 
 
 
Minimum and maximum pain scores in all study groups will be assessed via Numeric Rating Scale (0-10) 
 
as per Inova Health System (HIS) policy ‘Pain Management for the Adult Population’ at 24 hours, 48 
 
hour, 72 hours, and PRN with opioid request in all groups and administration follow up within one hour 
 
as per IHS inpatient medication administration policy Follow up scores will not be recorded as part of 
 
study procedure. 
 
3.3.2 Secondary Outcomes 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 8 of 13  
 
Secondary outcomes include decreased incidence of ileus, AST/ALT > 3x ULN (AST >168, ALT >105), 
post-operative tidal volumes as assessed by incentive spirometry, number of hours post CVICU arrival to 
extubation and analysis of medication and hospitalization costs. 
 
 
3.4   Consent/Assent 
 
Eligible subjects may only be included in the study after providing written (witnessed, where required by law 
 
or regulation), IRB -approved informed consent. If the subject is capable of doing so, he/she will indicate 
 
assent by personally signing and dating the written informed consent document.  Informed consent must be 
 
obtained by the Principal Investigator, Sub-Investigator, or the  Study Coordinator; individuals qualified to 
 
obtain informed consent before conducting any study-specific procedures (i.e., all of the procedures 
 
described in the protocol). The process of obtaining informed consent will be documented in the subject’s 
 
medical record as well as clinical trial source documents. 
 
 
 
 
3.4 Criteria for Withdrawal of Subjects from the Study.    
 
Subjects in the experimental groups will be withdrawn from the study if there is no enteral access beyond 
 
post- operative day 0, and for increased serum liver function values. 
 
4. STATISTICAL CONSIDERATIONS/DATA ANALYSIS 
 
 4.1 Sample Size 
Twenty subjects, 10 per arm (Group 1opiate based standard of care, and Group 2 multimodal regimen of IV 
APAP and PO gabapentin) to determine feasibility of larger study and determine estimates of primary 
outcome (i.e., total opioid consumption, pain scores, etc.) mean and variance parameters for sample size 
calculation for larger study to follow. Estimates for study attrition, and secondary outcomes of hospital length 
of stay, incidence of AST/ALT > 3x ULN, (AST >168, ALT >105) etc. will be calculated. 
 
 
4.2 Method of Data Analysis 
Although underpowered for this pilot, our statistical analysis plan is designed to similarly assess the 
feasibility of the larger study to follow. Primary analyses for this pilot will be to determine feasibility of 
larger study and determine estimates of primary outcome (e.g., total opioid consumption, pain scores, 
etc.) mean and variance parameters for sample size calculation. Estimates for study attrition, and 
secondary outcomes of hospital length of stay, incidence of AST/ALT > 3x ULN (AST >168, ALT >105) 
, etc. will be calculated. All analyses will be conducted as intent-to-treat. Data will be presented as mean 
± standard deviation or frequency and percent, where appropriate. Data will be assessed for departures 
from normality using Kolmogorov-Smirnov tests. Departures from normality will be treated using 
nonparametric tests (e.g., Wilcoxon, Kruskal-Wallis, etc.). However, given the short duration of the total 
patient enrollment and total patient time in study, we anticipate minimal missing data or patient attrition. 
Subjects with missing data ≥ 10% will be examined to determine if missing data is non-random.  
 
To test the primary hypothesis that for significant differences between groups, we will use separate GLM 
for total opioid consumption (repeated measures [3 time points], dependent variable [DV]), total number 
of breakthrough pain medication requests (DV) and medication cost (DV). Time points (n=3) to assess 
total opioid consumption and breakthrough pain medication requests will be at 24, 48 and 72 hours. 
Medication cost will be assessed once following discharge. An interaction term will be included for the 
group (n=2)* time (n=3) models (DV=total opioid consumption and breakthrough pain medication 
requests). Pain (dichotomized, pain score < 2) will be assessed using an unconditional binary logistic 
regression approach. Post-hoc testing for group comparison (Group 1 vs. Group 2) and group by time 
interaction (e.g., total opioid consumption only, etc.) will be performed using Tukey’s least significant 
difference test (LSD) for GLM models and estimation procedures (contrasts) for logistic regression 
(Group 1 vs. Group 2). To test the hypothesis that reduced opioid consumption will lead to a reduction in 
the incidence of ileus, incidence rates and 95% confidence intervals (CI) per group will be calculated and 
compared using conditional exact tests based on the binomial distribution. Secondary outcomes include 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
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CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 9 of 13  
 
hospital length of stay (LOS, days), antiemetic requirement, the incidence of AST/ALT > 3x ULN(AST 
>168, ALT >105) , the incidence of ileus during hospitalization will be calculated using either methods 
described above; GLM (LOS), unconditional logistic regression (antiemetic) or exact tests (AST/ALT, 
ileus).   
 
 
 
 
4.3 Data Storage 
 
4.3.1   Data Management 
 
Information about study subjects will be kept confidential and managed according to the 
 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Each subject 
 
screened and enrolled will be assigned a subject identification number (SID) and a list of subjects with 
 
their corresponding SID will be maintained separately from collected data. Physical case report forms 
 
(CRF’s) will be stored at the research site in a locked office and electronic subject data will be 
 
locked in a password protected file on a secure internet server, accessed only by authorized research 
 
staff. Only members of the research team will be able to access to this data on the secure server and the 
 
file password.  
 
 
4.3.2 Records Retention 
 
The Investigator will maintain the records of drug disposition, final CRFs (CDROM copies), worksheets, 
 
source documents, and all other study-specific documentation in accordance with ICH Guidelines. 
 
Essential documents should be retained for at least three (3) years after the investigation is formally 
 
discontinued.  
 
5. HUMAN SUBJECTS PROTECTION (RISKS, BENEFITS, AND    
ALTERNATIVES) 
 
 
5.1.1 Potential Loss of Privacy 
 
Protected health information (PHI) will be collected during the study. The risk for breach of confidentiality 
 
and privacy will be minimized by shielding the subjects unlinking his or her identity from his or her personal 
 
health information. 
 
 
5.1.2 Potential Adverse Events 
 
Aside from standard of care cardiac surgery practices and procedures, no other additional treatments or 
 
procedures will be given to subjects for this trial.  
 
 
5.2 Benefits and Alternatives 
 
There are no direct benefits to the patient. Participation in the study is entirely voluntary. The alternative is 
 
not to participate in the trial. 
 
 
6. SUBJECT COMPENSATION 
    
 
 
 
 
6.1 Costs 
 
 
 There are no costs to participate in the research study. 
 
 
 
 6.2 Payment  
 
 
There will be no payment to the subject for participation in the research study. 
 
7. ADVERSE EVENT REPORTING 
   
 
 
7.1 AE Recording 
 
 
Adverse events will be collected postoperatively. For the purpose of this study, only the following  
 
 
adverse  events will be collected and reported: 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
_______________________________________________________________________________________________ 
 
______________________________________________________________________________________________ 
 
CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 10 of 13  
 
 
Nausea 
 
Vomiting 
 
Paralytic Ileus 
 
        
7.2 Adverse Events Treatment 
 
 
Patients will be followed for clinical outcomes. All AEs and SAEs will be collected from   
 
 
randomization through 72 hours after randomization. 
 
               
 7.3 Adverse Event Documentation   
  
 
The principal investigator has the primary responsibility for SAE identification, documentation,  
 
 
grading, and assignment of attribution to the study intervention. SAEs must be recorded in the  
 
 
AE CRF with the following information:  
 
AE term 
 
The intensity grade (CTCAE v 4.03 grading) 
 
The relationship to study procedure 
 
Attribution 
 
Duration 
 
Occurrence (known risks for study procedure-expected, unexpected) 
 
Other contributing causes 
 
Actions in response to event 
 
Outcome 
 
Criteria for SAE  
 
      
7.4 AE Grading Scale 
 
 
The descriptions and grading scales found in NCI Common Terminology Criteria for Adverse Events 
 
 
(CTCAE) version 4.03 will be used for AE reporting. Each AE term is  associated with a 5-point  
 
 
severity scale.  
 
 
8. FUNDING 
 
This is an investigator-initiated study sponsored by Inova Heart and Vascular Institute. There is no 
investigational product involved. Treatment received by the subject will be as according to main provider’s 
discretion as according to standard of care.  
 
9. CONFLICTS OF INTEREST  
 
              The investigators declare no conflicts of interest linked to this study.  
 
10.  FACILITIES AND EQUIPMENT  
                                                         
The Inova Heart and Vascular Institute (IHVI) will be the only setting for this clinical trial. IHVI equipment will 
be utilized as necessary per standard of care. 
 
11. OUTSIDE CONSULTANTS/COLLABORATORS 
  
 
There are no outside consultants/collaborators participating. 
 
12. CONTRACTURAL AGREEMENTS  
  
   


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
_______________________________________________________________________________________________ 
 
______________________________________________________________________________________________ 
 
CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 11 of 13  
 
 
There are no contractual agreements in effect for this study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Opioid Sparing in Cardiac Surgery Pain 
 
Inova Heart and Vascular Institute 
_______________________________________________________________________________________________ 
 
______________________________________________________________________________________________ 
 
CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 12 of 13  
 
 
13. REFERENCES 
 
1 
Rafiq S, Steinbruchel DA, Wanscher MJ, et al. Multimodal analgesia versus traditional opiate based  
 
analgesia after cardiac surgery, a randomized controlled trial. J Cardiothorac Surg. 2014; 9(52). 
2 
Bigeleisen PE, Goehner N. Novel approaches to pain management in cardiac surgery. Curr Opin 
 
Anesthesiol. 2015; 28:89-94. 
3 
Mazzeffi M, Khelemsky Y. Poststernotomy pain: A clinical review. J Cardiothorac Vasc Anesth. 
 
2011; 25(6): 1163- 1178. 
4 
Douzjian DJ, Kulik A. Old drug, new route: A systematic review of intravenous acetaminophen after adult 
 
cardiac surgery. J Cardiothorac Vasc Anesth. 2017; 31: 694-701. 
5 
Menda F, Koner O, Sayin M, et al. Effects of single- dose gabapentin on postoperative pain and morphine 
 
consumption after cardiac surgery. J Cardiothorac Vasc Anesth. 2010; 24(5): 808- 813. 
6 
Liu SS, Wu CL. Effect of postoperative analgesia on major postoperative complications: A systematic update 
 
of the evidence. Anesth Analg. 2007; 104(3): 689-702. 
7 
Jelacic S, Bollag L, Bowdle A, et al. Intravenous acetaminophen as an adjunct analgesic in cardiac surgery 
 
reduces opioid consumption but not opioid- related adverse effects: A randomized controlled trial. J 
 
Cardiothorac Vasc Anesth. 2016; 30(4): 997-1004. 
8 
Roberts GW, Bekker TB, Carlsen HH, et al. Postoperative nausea and vomiting are strongly influenced by 
 
postoperative opioid use in a dose- related manner. Anesth Analg. 2005; 101: 1343-1348. 
9 
Sawatzky JV, Rivet M, Ariano RE, et al. Post- operative nausea and vomiting in the cardiac surgery 
 
population: Who is at risk? Heart Lung. 2014; 43: 550- 554. 
10 
Melnyk M, Casey RG, Black P, et al. Enhanced recovery after surgery (ERAS) protocols: Time to change 
 
practice? CUAJ. 2011; 5(5): 342- 348. 
11 
Bragg D, El-Sharkawy AM, Psaltis E, et al. Postoperative ileus: Recent developments in pathophysiology 
 
and management. Clin Nutr. 2015; 34(3): 367- 376. 
12 
Nearman H, Klick JC, Eisenberg P, et al. Perioperative complications of cardiac surgery and postoperative 
 
care. Crit Care Clin. 2014; 30: 527-555. 
13 
Sigakis MJG, Bittner EA. Ten myths and misconceptions regarding pain management in the ICU. Crit Care 
 
Med. 2015; 43(11):2468-2478. 
14 
Ucak A, Onan B, Sen H, et al. The effects of gabapentin on acute and chronic postoperative pain after 
 
coronary artery bypass surgery. J Cardiothorac Vasc Anesth. 2011; 25(5): 824-829. 
15 
Hansen RN, Pham AT, Boing EA, et al. Comparative analysis of length of stay, hospitalization costs, opioid 
 
use, and discharge status among spine surgery patients with postoperative pain management including 
 
intravenous versus oral acetaminophen. Curr Med Res Opin. 2017; 33(5):943-948. 
16 
Turan A, Karimi N, Zimmerman NM, et al. Intravenous acetaminophen does not decrease persistent surgical 
 
pain after cardiac surgery. J Cardiothorac Vasc Anesth. 2017; 31(6): 2058-2064. 
17 
Chou R, Gordon DB, de Leon-Casasola OA, et al. Guidelines for the management of postoperative pain. 
 
Management of postoperative pain: A clinical practice guideline from the American Pain Society, the 
 
American Society for Regional Anesthesia and Pain Medicine, and the American Society of 
 
Anesthesiologists’ Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J 
 
Pain. 2016; 17(2): 131-157. 
18 
Mamoun NF, Lin P, Zimmerman NM, et al. Intravenous acetaminophen analgesia after cardiac surgery: A 
 
randomized, blinded, controlled superiority trial. J Thorac Cardiovasc Surg. 2016; 152(3): 881-889. 
19 
Rapchuk IL, O’Connell L, Liessmann CD, et al. Effect of gabapentin on pain after cardiac surgery: a 
 
randomized, double- blind, placebo- controlled trial. Anaesth Intensive Care. 2010; 38(3): 445-451. 
20 
Ho KY, Gan TJ, Habib AS. Gabapentin and postoperative pain- a systematic review of randomized 
 
controlled trials. Pain. 2006; 126(1-3): 91-101. 
21 
Menda F, Koner O, Sayin M, et al. Effects of single- dose gabapentin on postoperative pain and morphine 
 
consumption after cardiac surgery. J Cardiothorac Vasc Anesth. 2010; 24(5): 808-813. 
22 
Dahl JB, Mathieson O, Moiniche S. ‘Protective premedication’: An option with gabapentin and related 
 
drugs? Acta Anaesthesiol Scand. 2014; 48: 1130-1136. 


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Inova Heart and Vascular Institute 
_______________________________________________________________________________________________ 
 
______________________________________________________________________________________________ 
 
CONFIDENTIAL             Opioid Sparing Protocol                       PI: Ramesh Singh MD                             Page 13 of 13  
 
23 
Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain. Visual analog scale for pain (VAS Pain), 
 
Numeric rating scale for pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short- form McGill pain 
 
questionnaire (SF-MPQ), Chronic pain grade scale (CPGS), Short form- 36 bodily pain scale (SF- 36 BPS0, 
 
and Measure of intermittent and constant osteoarthritis pain (ICOAP). Arthritis Care Res. 2011; 63 (supp. 
 
11):S240-252, 
24 
Karcioglu O, Topacoglu H, Dikme O, et al. A systematic review of the pain scales in adults: Which to use? 
 
Am J Emerg Med. 2018; Jan 6: S0735- 6757. 
25 
Yorkgitis BK, Brat GA. Postoperative opioid prescribing: Getting it RIGHTT. Am J Surg. 2015; Feb 6:1-5. 
 
 
 
 
 
 
 
 
 

ICF_001.pdf: 
Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 1 of 9 
Informed Consent for a Research Study 
 
 
Study Title: 
A Pilot Study Comparing the Effectiveness of an 
Opioid-Sparing Analgesic Regimen and an Opioid 
Based Regimen on Post- Operative Pain Control in 
Cardiac Surgery Patients (INOVA OPIOID) 
 
Principal Investigator:   
Ramesh Singh MD 
 
Site of Investigation:   
Inova Heart and Vascular Institute (IHVI) 
 
3300 Gallows Road 
 
Falls Church, Virginia 22042 
 
Study Related Contact Information: Patricia Saulino RN BSN MPA 
 
Senior Research Coordinator  
 
Cardiac Surgery and Critical Care Research IHVI 
 
patricia.saulino@inova.org 
 
703-776-4711 
 
Introduction 
You may be eligible to take part in a research study.  This research consent form gives you 
important information about the study.  It explains why this research study is being done, what is 
involved in participating in the research study, the possible risks and benefits of participation, 
choices for participation and your rights as a research participant.  
 
Please take your time to review this information carefully. You may also wish to talk to others 
(for example, your family, friends, or other doctors) about your participation. The decision to 
participate is yours. You may leave the study at any time without losing any benefits you would 
have normally received. If you decide to take part in the study, you will be asked to sign your 
name and the date at the end of this form.  We will give you a copy of the form so that you can 
refer to it while you are involved in this research study. We encourage you to ask questions now 
and at any time in the future. 
 
What if I am already participating in another study? 
Are you already participating in any other research studies?  Yes 
 
No 
 
If yes, please state which study (ies) _______________________________________________ 
 
While participating in this study, you may not take part in any other research study without 
approval from the principal investigator.  
 
Why is this study being done? 
The purpose of this study is to avoid the use of opioid based pain medications. Opioid 
medications can cause serious side effects which can include but are not limited to ileus, which is 
a blockage most commonly in the lower intestine but can occur anywhere along the intestinal 
tract. Ileus is considered an emergency and can require surgery. Other side effects associated 
with opioids are sedation or extra sleepiness that can lead to not being able to take deep breaths  


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 2 of 9 
which can result in a longer time before your standard of care surgical breathing tube can be 
removed, or may cause post- operative pneumonia due to lack of taking deep breaths. It is well 
known that opioids also have the potential to cause addiction and long term use can even 
increase a patient’s sensitivity to pain.  
 
Two groups will participate in this study after being randomly assigned. One group will receive 
the opioids that are currently given to patients as the standard of care for post- operative cardiac 
surgery pain. The second group or the study group will receive oral (by mouth) gabapentin and 
intravenous (IV) acetaminophen. Gabapentin is a medication that is usually used to control 
seizures.  Gabapentin affects certain nerves and chemicals in the body that are involved in 
seizures. But research has been done that has found that it is also effective in the treatment of 
nerve pain and it is frequently prescribed to treat nerve pain. While nerve pain is not the only 
reason for cardiac surgery pain it is a strong component of this type of pain. 
 
Intravenous acetaminophen is a non-steroidal anti- inflammatory medication and also a non-
opioid analgesic. Inflammation is the body’s response to tissue injury and it may cause heat, 
redness, swelling, and pain both inside your body where it cannot be seen and outside your body 
at the site of the surgical incision. An analgesic is a drug known to relieve pain. Both anti-
inflammatory and analgesic medications are used to treat pain. While the exact way 
acetaminophen reduces pain is not known, it is known that the medication acts on the central 
nervous system in many different ways.  
 
If chosen for the study group you will receive gabapentin by mouth and IV acetaminophen on a 
regular schedule as opposed to opioids which are given based on the patient’s report of their pain 
scores. Opioid medication will be available for breakthrough pain in the study group if you 
do not feel that you are experiencing acceptable pain relief using the gabapentin and 
acetaminophen alone. 
 
This research is being done because opioids cause harmful side effects as well as addiction. With 
millions of people currently addicted to opioids, addiction has become a national crisis. Many 
hospitals, healthcare providers and even the United States government are dedicated to research 
and programs that are aimed at providing acceptable pain relief and avoiding opioid based 
medications. 
 
How many people will take part in this study? 
About 20 people are expected to take part in this study.  
 
What other choices do I have if I do not take part in this study? 
If you decide not to take part in this study, you have other choices. For example: 
• you may choose not to participate in the study and receive opioid medication as needed 
after your surgery 
• you may choose to take part in a different study, if one is available 
• or you could decide not to be treated 
 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 3 of 9 
How long will I be in this study? 
If you decide to participate, you will be in this study for 72 hours post cardiac surgery, or until 3 
days after your surgery.  
 
What will happen if I take part in this research study? 
Most medications you will have are part of the usual approach for your cardiac surgery and will 
be given even if you do not join the study.  However, the medications that are part of the study, 
oral (by mouth) gabapentin and IV acetaminophen are different from the opioids that are usually 
given as part of your surgery. You will still be given opioid medication if you decide you are not 
getting enough relief from the study medications. 
 
If you agree to take part in the study, you will be “randomized” into one of the study groups. 
Randomization means that you are put into a group by chance, like flipping a coin. Neither you, 
nor your doctor will choose what group you will be in.  You will have a 1 in 2 chance of being in 
any group.  
 
Study groups: 
This study has 2 study groups. 
1. Patients receiving opioids after cardiac surgery which is the current standard of care.  
2. Patients not receiving opioids but receiving the pain relief alternatives of oral gabapentin 
and IV acetaminophen with opioid medication for breakthrough pain if necessary.  
 
If you are randomized to the group that will receive non opioid medications, you will be given 
IV acetaminophen and oral gabapentin immediately after your procedure and then IV 
acetaminophen every six hours and oral gabapentin every 8 hours.  Both medications will be 
scheduled and given to you regularly for 40-42 hours (unlike opiates that must be requested for 
every dose). You will be asked to report your pain score every 12 hours. Opioid medications will 
be available to you for breakthrough pain. If you should need an opioid medication, you will 
report your pain score to the nurse or the doctor and you will be given the opiate prescribed for 
the level of pain  you reported. You will also report your pain score 1 hour after administration. 
 
If you are randomized to the standard of care group, you will be given opiates that will vary 
based on the pain score you report to your nurse or your doctor. You will report your pain score 
before you receive the opioid medication and 1 hour after. For the study purposes, you will be 
asked to report your pain score every 12 hours. 
 
What side effects or risks can I expect from taking part in this study? 
If you choose to take part in this study, there is a risk that you may:   
• The most important non-medical risk is the disclosure of your protected health 
information (PHI). PHI is any health information that is collected about you, including 
your history and new information collected during this study. You will have an 
opportunity to review the ways in which your PHI may be used and disclosed in the 
separate HIPAA Authorization for Research form. 
 
There is also a risk that you could have side effects. 
 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 4 of 9 
 
Here are important points about side effects: 
• The study doctors do not know who will or will not have side effects. 
• Some side effects may go away soon, some may last a long time, or some may never go 
away. 
• Some side effects may interfere with your ability to have children. 
• Some side effects may be serious and may even result in death. 
 
Here are important points about how you and the study doctor can make side effects less of a 
problem: 
• Tell the study doctor if you notice or feel anything different so they can see if you are 
having a side effect. 
• The study doctor may be able to treat some side effects. 
 
The table below shows the most common and the most serious side effects that researchers know 
about.  There might be other side effects that researchers do not yet know about.  If important 
new side effects are found, the study doctor will discuss these with you. 
Risks and side effects related to Oral Gabapentin1 include those which are:  
 
 
 
 
 
 
 
 
 
 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 5 of 9 
 
Risks and side effects related to Intravenous Acetaminophen2 include those which are:  
 
1https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf 
2https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022450lbl.pdf 
 
You should talk to your study doctor about any side effects that you have while taking part in the 
study.  
 
Are there reproductive risks while on this study? 
You should not get pregnant, breastfeed, or father a baby while on this study because we cannot 
predict the effects on an unborn baby.  
 
A pregnancy test will be performed on all women who may be pregnant before taking part in this 
study.  This includes all women except those whose menstrual periods have not occurred for 
more than one year after menopause (change of life) or those who have had sterilization surgery 
(tubes tied) or a hysterectomy (removal of the uterus or womb).  Pregnant women may not take 
part in this research study. 
 
If you decide to take part in this study, you must agree to protect yourself or your partner from 
becoming pregnant. If you or your partner becomes pregnant when either parent is taking the 
drug, birth defects may occur.  If you are a female and think that you might be pregnant, you 
must immediately tell your study doctor. It may be harmful for a child to breastfeed from a 
woman taking a study drug. Because of this, female participants must not breastfeed during the 
study and for (insert number of days/weeks) after the study ends. 
 
If you become pregnant while taking study drug, you will agree to release your health records 
while pregnant. You will also agree to release your child’s health records for the first year of 
his/her life.  
 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 6 of 9 
 
 
Acceptable methods of contraception (birth control) while taking part in this study are: 
1. Total Abstinence (no sexual intercourse), absence of menstrual periods in women for 
more than one year after menopause (change of life), and sterilization surgery, including 
tubal ligation (tubes tied) or hysterectomy (removal of the uterus or womb) in women or 
a vasectomy in men. 
2. Oral contraceptives (birth control pills), intrauterine device (IUD), implantable or 
injectable contraceptives (Norplant or Depo-Provera), contraceptive patch, vaginal ring 
or use of condom with spermicide.  These methods must be used exactly as directed. 
 
The following methods of contraception are not acceptable to prevent pregnancy during 
study participation: diaphragm, cervical cap, vaginal sponge, and “female condom”. 
 
Are there benefits to taking part in this study? 
Taking part in this study may or may not make your health better.  We hope the information 
learned from this study will benefit others in the future. 
 
Can I stop being in the study? 
Yes. You can choose not to be in the study. You can decide to stop at any time. It is important to 
tell the study doctor if you are thinking about stopping or leaving the study.  
 
Your participation can also be stopped without your approval by any of the following: 
• the study doctor  
• the Institutional Review Board (IRB – hospital committee that reviews and approves 
research),  
 
The study doctor may decide to take you off this study for any of the following reasons: 
• If your health changes and the study is no longer in your best interest 
• If new information becomes available 
• If you do not follow the study rules 
 
What are the costs of taking part in this study? 
You will not be responsible for the cost of study medications (acetaminophen and gabapentin) 
used as are a part of the study. 
 
You and/or your health plan/ insurance company will need to pay for some or all of the costs of 
your cardiac surgery while in this study. Check with your health plan or insurance company to 
find out the total costs to you for treatment while on this study. You may be responsible for any 
co-payments and deductibles that are standard for your insurance charges  
 
Will I be paid for taking part in this study? 
You will not be paid for taking part in this study.   
 
What if I am injured because I took part in this study? 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 7 of 9 
In the event that you believe you have been injured because of taking part in this study, it is 
important that you call your study doctor.  You can call Dr. Ramesh Singh, principal 
investigator, at 703- 280-5858 and he will review the matter with you.  Inova Health System and 
the study doctor do not provide funds or free medical treatment for injuries that result from 
taking part in this study.  Medical treatment is available to you if you are injured as a result of 
taking part in this study. 
You and/or your health plan will be billed for the cost of this care. If your insurance does not pay 
for your care, or pays only a portion of the cost of such care, you may be billed for any unpaid 
amounts. 
 
You should not expect anyone to pay you for pain, worry, lost income, or non-medical care costs 
that occur from taking part in this research study.  No funds have been set aside, by Inova Health 
System and Inova Cardiac and Thoracic Surgery to repay you in case of injury.  
 
You are not waiving any legal claims or rights because of your participation in this study.  
 
Will my medical information be kept private? 
We will keep your records private to the amount allowed by law.  Research records are stored 
and kept according to legal requirements. You will not be identified in any reports or 
publications about this study.  However, certain people and groups will have access to your 
research and medical records.  The Inova Health System Institutional Review Board (IRB) and 
federal and state agencies that have authority over the study may look at your research records.  
Members of the study staff will also have access to your research records.  Additional groups, 
explained in the HIPAA Authorization for Research form may also have access to these records. 
 
You will be assigned a Patient Identification Number (PIN), e.g. 001, and this will be used to 
identify your study information.  This PIN will be correlated with your name and medical 
information in a separate locked location. 
 
What are my rights if I take part in this study? 
Taking part in this study is your choice.  No matter what decision you make, and even if your 
decision changes, there will be no penalty to you. You will not lose medical care or any legal 
rights. A member of your research team will tell you about new information or changes in the 
study that may affect your health or your willingness to continue in the study. 
 
If you would like more information about your rights as a participant in a research study, contact: 
Inova Health System Institutional Review Board (IRB) at 571-472-3458. The Inova Health 
System IRB may contact you by mail or telephone to find out if you were satisfied with your 
study participation. 
 
Who can answer my questions about the study? 
You can talk to your study doctor about any questions or concerns you have about this study. 
Contact your study doctor Ramesh Singh MD at703- 280-5858 or the study coordinator Patricia 
Saulino RN at 703-776-4711. 
 
Where can I get more information? 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 8 of 9 
A description of this clinical trial will be available on www.ClinicalTrials.gov, as required by 
U.S. Law. This Web site will not include information that can identify you. At most, the Web 
site will include a summary of the results. You can search this Web site at any time. 


Short Title: INOVA OPIOID (18-3002) 
Principal Investigator: Ramesh Singh, MD 
RESEARCH CONSENT  
Date Approved: May 15, 2019 
Inova IRB: Joanne Muratori, IRB Coordinator 
IRB File #18-3002  
 
 
Protocol date: 12/10/2018 
Consent Version: #4, April 2019 
 
Page 9 of 9 
 
Signature 
You, the undersigned have been informed about this study’s purpose, procedures, possible 
benefits and risks, and you have read this consent and received a copy of this consent, including 
the separate HIPAA authorization form to use and disclose protected health information.  You 
have been given the opportunity to ask questions before you sign, and you have been told that 
you can ask other questions at any time.  You voluntarily agree to give your consent to 
participate in this research study. 
 
You are free to withdraw from the study at any time and you do not have to say why you no 
longer wish to participate.  You will notify the Principal Investigator if you are leaving the study 
because of any side effects you might experience.  This withdrawal will not in any way affect 
your future treatment or medical management.  You agree to cooperate with the Principal 
Investigator and the research staff and to inform them immediately if you experience any 
unexpected or unusual symptoms. 
 
 
______________________________________     _______________________ 
___________ 
Signature of Subject 
Printed Name of Subject 
Date  
 
 
________________________________ 
_______________________ 
_________________ 
 
As a member of the research team, I have explained the purpose, the procedures, the benefits and 
risks that are involved in this research study. Any questions that have been raised have been 
answered to the individual’s satisfaction. 
 
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Signature of Person Obtaining Consent      
Printed Name 
 
 
Date   
 
 
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Signature of Witness 
Printed Name of Witness 
 
Date