Clinical trial NCT03678675
Conditions: Post-operative Pain Post-partum Pain Cesarean Section Complications
Keywords: ketorolac opiate cesarean section
Sponsor: Tufts Medical Center
Start date: 2019-05-30; Completion date: 2022-06-30
Enrollment: 148 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To evaluate the efficacy of increased ketorolac in reducing opioid use after cesarean section.

Detailed description:
This was a single-center, randomized, double-blind, parallel-group trial to assess pain management following cesarean section with increased ketorolac versus placebo. All patients undergoing cesarean section with neuraxial anesthesia received two doses of 30mg IV ketorolac postoperatively per hospital protocol and were then randomized to receive an additional four doses of 30 mg of IV ketorolac or placebo every 6 hours. The primary outcome was the total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients that used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) was planned.

Arms: arm 1: Subjects randomized to the standard group will receive the standard postoperative pain protocol that is currently used at Tufts Medical Center. It includes two doses of IV Ketorolac every 6 hours as needed for postoperative pain. Ibuprofen would be ordered 6 hours following the last dose after the last study drug. arm 2: Subjects randomized to the Ketorolac protocol will receive the study postoperative pain protocol. This includes 6 doses of IV Ketorolac, scheduled every 6 hours. The first dose is administered in the operating room or post-operative care unit.
Interventions: intervention 1: Ketorolac
Intervention descriptions: intervention 1: The intervention is a protocol of scheduled IV Ketorolac administered postoperatively.

Protocol documents:
Prot_SAP_000.pdf: 
PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 1 of 18 
 
 
STUDY TITLE: 
Scheduled Ketorolac administration after cesarean section and its effect on opioid use: a 
randomized control trial 
 
 
PRINCIPAL INVESTIGATOR 
Name:  Michael House, MD 
Department Obstetrics and Gynecology, Division of Maternal Fetal Medicine 
Telephone Number: 617-636-4549 
Email Address mhouse@tuftsmedicalcenter.org 
NCT03678675 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tufts Health Sciences IRB 
Protocol Template 
Template Revised: 08/16/2016 
 
 
 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 2 of 18 
 
 
1. 
Study Schema .................................................................................................................................................3 
2. 
Introduction ....................................................................................................................................................3 
2.1 
Background and Rationale .........................................................................................................................4 
2.2 
Risks to Subjects.........................................................................................................................................5 
2.3 
Potential Benefits to Subjects .....................................................................................................................5 
2.4 
Alternatives.................................................................................................................................................6 
3 
Objectives .......................................................................................................................................................6 
4 
Enrollment and Withdrawal............................................................................................................................6 
4.1 
Inclusion Criteria ........................................................................................................................................6 
4.2 
Exclusion Criteria .......................................................................................................................................6 
4.3 
Withdrawal of Subjects ..............................................................................................................................7 
4.4 
Recruitment and Retention .........................................................................................................................7 
4.4.1 
Local Recruitment Methods ...............................................................................................................7 
4.4.2 
Study-Wide Recruitment Methods .....................................................................................................7 
4.4.3 
Payment ..............................................................................................................................................8 
4.4.4 
Reimbursement ...................................................................................................................................8 
5 
Study Design ..................................................................................................................................................8 
5.1 
Study Timelines ..........................................................................................................................................8 
5.2 
Procedures ..................................................................................................................................................8 
5.3 
Evaluations ...............................................................................................................................................10 
5.4 
Collection and Storage of Human Biological Specimens (Tissue Banking) ............................................10 
6 
Ethics and Protection of Human Subjects ....................................................................................................10 
6.1 
Informed Consent Process ........................................................................................................................10 
6.2 
Waiver or Alteration of Consent Process .................................................................................................11 
6.3 
International Research ..............................................................................................................................11 
6.4 
Confidentiality ..........................................................................................................................................11 
6.5 
Provisions to Protect the Privacy Interests of Subjects ............................................................................11 
6.6 
Provisions to Monitor the Study to Ensure the Safety of Subjects ...........................................................12 
6.7 
Compensation for Research-Related Injury..............................................................................................12 
6.8 
Economic Burden to Subjects...................................................................................................................12 
6.10 Vulnerable Populations ................................................................................................................................12 
7 
Adverse Event Monitoring ...........................................................................................................................13 
7.1 
Definitions ................................................................................................................................................13 
7.2 
Reporting Procedures ...............................................................................................................................13 
7.3 
Reportable New Information ....................................................................................................................14 
8 
Statistical Considerations .............................................................................................................................14 
8.1 
Study Endpoints........................................................................................................................................14 
8.2 
Statistical Analysis ...................................................................................................................................14 
8.3 
Number of Subjects ..................................................................................................................................15 
8.4 
Data Management .....................................................................................................................................15 
8.5 
Randomization ..........................................................................................................................................16 
9 
Drugs or Devices ..........................................................................................................................................16 
10 
Study Administration ....................................................................................................................................16 
10.1 
Setting .......................................................................................................................................................16 
10.2 
Registration...............................................................................................................................................17 
10.3 
Resources Available .................................................................................................................................17 
10.4 
IRB Review ..............................................................................................................................................17 
10.5 
Multi-Site Research ..................................................................................................................................17 
10.6 
Community-Based Participatory Research ...............................................................................................17 
10.7 
Sharing Results with Subjects ..................................................................................................................17 
11 
References ....................................................................................................................................................17 
 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 3 of 18 
 
1. Study Schema 
 
 
 
1. Exclusion criteria: see section 4.2 for full list of exclusion criteria 
 
2. Introduction 
Women undergoing 
cesarean delivery 
during study period
Women not 
assessed for 
eligibility
Women consented
Excluded due to 
meeting exclusion 
criteria1 
Randomized
Allocated to study 
group
Did not receive 
study protocol
Received Study protocol: 
2 doses of 30mg IV 
ketorolac and 4 
additional scheduled 
doses every 6 hours
Cases Analyzed
2 week follow up 
phone call
Allocated to 
standard group
Did not receive 
standard protocol
Received standard protocol; 
2 dosees of 30mg IV 
ketorolac and 4 scheduled 
doses of saline every 6 hours.
Cases analyzed
2 week follow up 
phone call


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
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Page 4 of 18 
 
2.1 Background and Rationale 
Post-operative pain control is an issue not only in regards to patient satisfaction, but also patient 
outcomes.  Pain in the early postpartum period can interfere with a woman’s ability to care for herself and her 
infant. 1 Over-prescription as well as misuse of narcotic pain medications across the United States has been a 
popular topic of investigation.  Compared to other surgical subspecialties, there is a paucity of literature regarding 
effective methods to decrease post-operative narcotic use in obstetric units, especially in the immediate 
postpartum period2.  Our study evaluates how a protocol of scheduled non-narcotic analgesic used in the 
immediate post-operative period affects the amount of oral narcotic medication administered and patient pain 
scale scores.  
A retrospective cohort study 3was conducted to evaluate the difference in oral narcotic 
requirements postoperatively after implementing a new post-operative pain management protocol.  This 
study included two hundred and eight cesarean sections, 3 of which were excluded for allergies to either 
hydrocodone/acetaminophen (HA) or NSAIDs.  110 women were in the standard protocol group and 95 
were in the Ketorolac protocol group.  The subjects in the standard group received up to 2 doses of 30mg 
of IV Ketorolac in the post operative period.  The subjects in the Ketorolac group received 6 scheduled 
doses of 30mg IV Ketorolac during their post operative course.  On average, the standard group received 
5.39 doses (±4.682) of hydrocodone10mg/acetaminophen (H10A) and the Ketorolac group received an 
average of 3.44 doses (±4.544) of H10A. See table below.   Assuming equal variance, a t-score of 3.026 
(CI 0.680-3.226) was calculated, with a P value of .003 for doses of H10A administered. After a 
secondary analysis of the data, a significant difference in the amount of hydrocodone5mg/acetaminophen 
(H5A) required by the Standard protocol and the Ketorolac protocol was identified in patients who 
underwent a primary cesarean section (3.84 vs. 2.39, respectively. P= 0.031) Those who underwent repeat 
cesarean section had similar outcomes as the total sample, in that those in the Ketorolac group required 
less doses of H10A post operatively (5.49 Standard Group, 3.13 in Ketorolac group, P = 0.026).  When 
these doses of H5A and H10A were converted to MME, the study group consumed an average of 
69.9MME and the Ketorolac group consumed an average of 47.3 MME. The Ketorolac group consumed 
approximately 33% less MME than the standard group.  This data supports that scheduled Ketorolac in 
the post cesarean section population, may help to decrease the amount of narcotic required while in house.  
We hypothesize that subjects who receive scheduled IV Ketorolac during the post-operative period will 
require less morphine milligram equivalents than those receiving the standard pain control protocol. A 
randomized controlled trial, would allow us to test this hypothesis. We hypothesize that there will be a 
difference in the secondary outcomes as well; that both the pain scores and overall patient satisfaction, as 
evaluated by phone call, will be improved for the study group.     
 
Pain Scores, HA Doses Before and After Implementing Ketorolac Protocol 
Variable 
Standard Protocol 
Ketorolac Protocol 
P 
Pain Score*** 
 
 
 
6 hours 
3.20±2.579 
2.93±2.505 
0.444 
12 hours 
3.26±2.577 
3.35±2.753 
0.820 
24 hours 
4.21±2.709 
3.88±2.508 
0.368 
48 hours 
3.45±2.611 
3.62±2.667 
0.663 
Opioid Dose 
 
 
 
H5A* 
3.20±3.117 
2.60±2.251 
0.112 
H10A* 
5.39±4.682 
3.44±4.544 
0.003 
***Based on a 100mm visual analog pain scale 
*In number of doses, hydrocodone5mg/acetaminophen (H5A), hydrocodone10mg/acetaminophen (H10A) 
Data are mean±standard deviation 
P values are determined using Students t test for parametric data and 2 for categorical variables 
 
Post-operative pain is typically controlled using a stepwise, multimodal approach4 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
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.  Although this approach was initially developed for the treatment of cancer pain, it can be 
adapted to postoperative and postpartum pain.1 A stepwise approach refers to administering medications 
based on the patient’s level of pain. Pain can be assessed with a visual analog scale (VAS)5.   A 
multimodal approach refers to using medicines with varying mechanisms of action to control pain.  
Typically, a combination of nonsteroidal anti-inflammatory drug (NSAID) and an opioid are used during 
the postpartum period1.   
Given the relatively recent opioid epidemic in the United States, the Substance Abuse and Mental Health 
Services Administration has identified opioids as the most commonly abused prescription drug in the United 
States6.  Additionally, over prescription of narcotic pain medications has been associated with the increase of 
overdose deaths involving opioids.6 Efforts to decrease the amount of opioids dispensed in the hospital and 
prescribed as an outpatient can help decrease the propagation of this epidemic.  
NSAIDs like Ketorolac combine analgesic and anti-inflammatory properties. Ketorolac’s efficiency 
which is comparable to morphine, with a longer duration of action and fewer adverse effects.7 Ketorolac has been 
shown to have a morphine-sparing effect in orthopedic and gynecologic surgery.8–10There is data to support that 
Ketorolac is a safe and effective analgesic for the postpartum patient.10–13 However, there is a paucity of literature 
that evaluates the effect of scheduled intravenous Ketorolac on the amount of oral narcotic administered in the 
postpartum period.   
Is there an active control group?   
Yes
No
  
2.2 Risks to Subjects 
Foreseeable risks, discomforts, hazards and/or inconveniences include; 
1. Adverse reaction to Ketorolac.  The probability of this is low and the magnitude of the 
reaction is unpredictable. Adverse reactions are typically quickly and effectively reversed 
when recognized quickly. Side effects of Ketorolac are rare, but can potentially include 
headache, upset stomach, nausea, vomiting. Other side effects or risks of Ketorolac include 
gastrointestinal bleeding, ulceration and perforation, kidney failure, hemorrhage, renal 
papillary necrosis and other renal injury, cardiovascular thrombotic events, myocardial 
infarction and stroke, hypertension, congestive heart failure and edema, skin reactions, 
increased liver function tests, anemia and anaphylaxis.  Precautions will be in use with 
patients with a history of asthma.  
2. Therapy with other NSAIDs will not be administered to subjects.   
3. Discomfort or pain at peripheral IV line.  The probability of this is low and the magnitude is 
small.  The discomfort can easily be treated or reversed. An IV will be kept in place for nor 
longer than the standard time frame.  Patients who are tolerating PO can have the IV removed 
if they wish.  Those in the study group, however, need an IV for drug administration.  
Women who are assigned to the study plan will need to have an intravenous catheter 
in place for the first 24 hours after leaving the operating room.  Typically, the IV is 
removed about 12 hours after a patient leaves the operating room. Loss of privacy of 
protected health information.  The probability of this is low because the study database will 
be kept on a password protected computer in a locked office.   
4. Ketorolac is approved by the American Academy of Pediatrics and considered safe for 
breastfeeding moms and babies (L2 risk category). Any adverse events experienced by the 
subject or her newborn during the study will be promptly discussed with the newborn’s 
healthcare provider. 
2.3 Potential Benefits to Subjects 
There is no direct benefit to the study participants.  
Potential benefits may include: 
1. Decreased postoperative pain. This benefit could potentially aid in faster recovery 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 6 of 18 
 
2. Decreased need for opiate medications.  This benefit could also lead to enhanced recovery 
with quicker return of bowel function and decreased drowsiness.  
3. Decreased amount of opiate medications 
2.4 Alternatives 
The alternative is to NOT participate in the research study. Patients who forgo 
participation in the research study will receive the standard post-operative pain protocol. The 
standard clinical care includes oral ibuprofen and acetaminophen, as well as intravenous 
Ketorolac on an as needed basis.  Patients who do not participate in the trial may receive 
Ketorolac if they request pain medications during the first 18 post-operative hours.  
3 Objectives 
      Our study evaluates how a protocol of scheduled non-narcotic anesthetic used in the 
immediate post-operative period affects morphine milligram equivalents (MME) for oral narcotic 
medication administered.  The objective of the study is to identify a post-operative pain control 
regimen that can decrease the MME administered in the post-operative period.  
The primary outcome will be the amount of morphine milligram equivalents (MME) used in 
each group.  Secondary outcomes will include pain scores, postoperative complete blood count, 
post operative vaginal bleeding, and post-operative satisfaction with care received during 
admission.  
4 Enrollment and Withdrawal  
4.1 Inclusion Criteria 
Women presenting for care at Tufts Medical Center as an outpatient in obstetrics clinic or 
on Labor and Delivery and undergo a cesarean section for any indication at Tufts Medical Center, 
and who are willing to have a phone call follow up conversation 2 weeks after their surgery.   
There is no age eligibility. All of the subjects will be pregnant women.  Some of these subjects 
may be pregnant minors.   
4.2 Exclusion Criteria 
1. Subjects under the age of 16 years old.  
2. Patients with allergy to Ketorolac,  NSAIDS or aspirin 
3. Patients with peptic ulcer disease, preexisting kidney or liver disease.  
4. Duramorph is not used as the anesthetic for the spinal/epidural during the cesarean section.  
5. Patient is hemodynamically unstable due to hemorrhage. 
6. Patient requires therapeutic anticoagulation in the post-operative period 
7. Patients with peripartum cardiomyopathy, other cardiocascular disease, or history of 
congestive heart failure or cardiac decompensation.  
8. Patients with HEELP, eclampsia, pre-eclampsia or hypertension 
9. Patients with coagulation disorders, or bleeding diatheses 
10. Patients taking probenecid or pentoxifylline 
11. Past history of Stevens-Johnson Syndrome, toxic epidermal necrolysis 
12. Recent history of gastrointestinal bleeding, suspected or confirmed cerebrovascular bleeding, 
hemorrhagic diathesis, incomplete hemostasis 
13. Patients with a history of asthma, urticaria or allergic-type reactions after taking aspirin or 
other NSAIDS 
14. Patients who are currently receiving a full dose of aspirin or NSAIDs 
15. Patients who have an epidural or intrathecal administration 
16. Emergent circumstances where there is not sufficient time to perform informed consent.  
17. Provider decision to exclude patient. 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 7 of 18 
 
18. ***A study subject may participate in any other research study while participating in this 
research study. Participation in another research study is not an exclusion criteria for this 
study.  
4.3 Withdrawal of Subjects 
Anticipated circumstances under which subjects will be withdrawn from the research 
without their consent: 
1. Adverse reaction to Ketorolac 
2. If an above mentioned exclusion criteria develops, the study drug will be stopped.  
3. This is an intent to treat study.  The patient’s will remain in the group that they are 
randomized too. 
4. If a subject requires additional pain medication, the subject will get an opioid medication, 
as is current practice.   
5. A creatinine value will be measured on POD#1 and POD#2.  If creatinine is equal to or 
greater than 1.2mg/dL, then the study drug will be stopped. If the incidence of creatinine 
values equal to or greater than 1.2mg/dL reaches 5% of the subjects, the study will be 
stopped for safety.15  
 
Information collected on subjects prior to withdrawal from the research study will be 
included in the final analysis.  No additional specific safety precautions are necessary for 
subjects who withdraw or are withdrawn aside from routine post-operative care.    
4.4 Recruitment and Retention 
4.4.1 
Local Recruitment Methods 
Describe the following attributes of the recruitment plan for the local Tufts site:  
Subjects will be recruited either in their prenatal visits, when their cesarean section is 
scheduled, or upon presentation to labor and delivery. They will be interviewed and 
consented by the principle investigator, co-investigator another member of the research 
team. If they are consented during their prenatal visit, the subject will have several days 
to weeks to consider participation.  If they subject is consented upon admission to labor 
and delivery, then they will have hours to consider participation.  Patients in emergent 
circumstances where there is not sufficient time to perform informed consent will not be 
enrolled or approached for participation in this study. 
The first study visit will be consent and enrollment.  This visit may occur during a 
patient’s prenatal visit or at the time of admission to labor and delivery.  Subjects will be 
from the maternal fetal medicine and general obstetrics clinics at the main Tufts Medical 
center, as well as any patents admitted to Tufts Labor and Delivery unit.   
Potential subjects will be identified by clinicians in the outpatient clinics and on labor and 
delivery.   
5 
Patients may also be consented remotely. This situation may arise when their prenatal care 
is not at Tufts or if they are having prenatal care over telemedicine. Additionally, patients 
that present to labor and delivery for planned vaginal delivery may be consented for the 
study in the event that they have a cesarean section. I have reviewed HRP-092 and will 
follow this policy. We will follow SOP: remote informed consent process HRP-092 if 
consent is not obtained in person. 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 8 of 18 
 
5.4.1 
Study-Wide Recruitment Methods 
Is this is a multicenter study where subjects will be recruited by methods not under the control of 
the local Tufts site (e.g., call centers, national advertisements)?  
Yes
No
 
5.4.2 
Payment  
Will subjects receive money, gifts, or any other incentive for participating in this study?  
Yes
No
     
5.4.3 
Reimbursement   
Will subjects be reimbursed for their expenses, such as travel, parking, meals, or any other study 
related costs? 
Yes
No
   
                                  
6 
Study Design 
5.1 Study Timelines 
The subject’s participation will last a total of 2 weeks.  This time will span from immediately after 
delivery until 2 weeks postpartum.  
The enrollment period is anticipated to last 6 months. 
The estimated date of completion of this study is May 2022.  
The first study visit will be consent and enrollment.  This visit may occur during a patient’s 
prenatal visit or at the time of admission to labor and delivery.  A phone call conversation at the 2 
week postpartum mark will occur. This phone call will include a series of 9 questions and should 
take about 10 minutes to complete.  
 
5.2 Procedures 
 
Is there a placebo control arm?  
Yes
No
  
All patients who are seen at Tufts Medical Center for maternal fetal medicine or general obstetric 
care in the outpatient setting will be screened. They will be consented and enrolled if eligible at 
that time.  See section 4.4.1.  All patients who are not already screened or enrolled will be 
screened upon admission to Tufts Medical Center Labor and Delivery unit.   
A full medical history and physical examination is routinely performed.  The H&P will be 
reviewed prior to consenting the patient to assess for exclusion criteria.  Also, permission of the 
attending surgeon will be solicited prior to consent.   
Ketorolac is the drug used in this research.  It is already used routinely on Labor and Delivery at 
Tufts Medical Center, as well as the Mother-Infant Unit.  
Subjects who consented to be part of the trial will be randomized at the time of skin closure of 
their cesarean section to either the standard group or the study group. These groups will be 
blinded to the subjects and providers.  If a serious adverse reaction occurs during the study 
period, that subject may become unblinded. The investigational drug pharmacy services (IDS) 
will have the randomization scheme and will assign the subject to either study or standard group. 
A paper order will be faxed down to the IDS pharmacy one the subject leaves the operating room 
after her cesarean section.  This paper order will be signed by either the PI or a co-investigator of 
the study.  The standard group will receive the standard treatment of 2 doses of 30mg IV 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 9 of 18 
 
Ketorolac and the remaining 4 doses of placebo (normal saline). The study group will receive 6 
doses of 30mg IV Ketorolac scheduled every 6 hours.  Ketorolac is FDA approved for safety at 
this dosage.  The subject will receive her first dose in the operating room.  A dose of Ketorolac 
will be administered in the OR to all subjects.  This will be administered by anesthesia. Of note, 
any intrathecal or epidural catheters will be removed prior to administration of Ketorolac.  The 
Ob/Gyn residents will be responsible for placing the orders in Soarian and to fill out the IDS 
paper order form. These duties are within the scope of their regular job duties as resident 
physicians.  Please see below for sample order set.  Pain scores will be evaluated using a visual 
analog pain scale every 6 hours throughout hospitalization and recorded in the electronic medical 
record per standard of care.  The amount of oral opiate medications administered for subjects in 
each group will be recorded in the electronic medical record as well.  Pre operative and Post 
operative day #1 hematocrit values will be recorded. This is a routinely performed test, but will 
be providing data for the research. The number of peripads used will be collected and weighed as 
a means to estimate post partum vaginal bleeding for the first 24 hours post partum. Post 
operative day #1 and #2 serum creatinine measurements will also be obtained.  The first will be 
obtained at the same blood draw as the hematocrit measurement. The POD#2 measurement will 
be an additional blood draw.   
An intent-to-treat analysis will be used and a per-protocol analysis will be conducted among those 
who complied with the protocol.   
Data will be collected in the electronic medical record system while the subject is admitted to 
Tufts Medical Center.  A phone survey will be conducted 2 weeks from the delivery date.  Survey 
is attached as separate document. If the participant does not answer, the caller will leave a 
voicemail. The voicemail transcript is attached.  One additional attempt will be made to call the 
patient within 24 hours of the first call. The phone survey 2 weeks later is the only visit that is 
solely for research purposes.  
Sample Soarian Order Set: 
Post-Operative Pain Control Study Order Set  
 Ketorolac (Toradol) 30mg IV x 2 doses Q6hrs starting in OR  
 = then Post-Operative Pain Control Study IV injection, q6hrs x 4 doses  
 18 hours after intrathecal/epidural morphine, if patient tolerating fluids by mouth, patient may have 
oral acetaminophen or Percocet 
o Acetaminophen 650mg 1 TAB Q6PRN pain 1-3 
o Oxycodone5 1 TAB Q4HPRN pain 4-6  
o Oxycodone 5 2 TAB Q4HPRN pain 7-10 
 If patient has pain prior to 18 hours after intrathecal/epidural morphine that is not controlled, the RN 
is to page OB resident to evaluate patient and place an order for pain medication. 
 
Schedule of Events 
Recruitment 
At prenatal visit or admission to labor and 
delivery at Tufts Medical Center 
Randomization 
At time of skin closure in operating room 


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a randomized control trial  
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Study Group 
 Ketorolac 30mg IV q6hours x 2 doses 
 then Ketorolac 30mg IV q6hrs x 4 doses 
First dose in the operating room. The remaining 
doses will be administered on L&D or mother-
infant unit.  
Standard Group 
 Ketorolac 30mg IV q6hrs x 2 doses 
 then 4 doses of placebo, q6 hours 
First dose in the operating room. The remaining 
doses will be administered on L&D or mother-
infant unit. 
Morphine Milligram equivalents (MME) measured 
using a MME conversion calculator14 
 
 
Example: Oxycodone is 1.5 MME 
 
The MME’s used by each subject will be 
measured from the time the patient arrives to the 
recovery room until post operative hour 72 
(approximately post operative day #3, as this is 
the standard amount of time patients stay in the 
hospital after a cesarean section.)  
Cases will be analyzed 
Upon patient discharge 
Phone call 
2 weeks after discharge 
Data Analysis 
 
5.3 Evaluations 
Will you perform any laboratory tests for this study?  
Yes
No
  
A complete blood count will be collected and values recorded.  This laboratory test is standard of care and 
not solely for the purpose of this study.  
5.4 Collection and Storage of Human Biological Specimens (Tissue Banking) 
Will biological specimens be stored for future, unspecified, research?   
Yes
No
  
 
6 Ethics and Protection of Human Subjects 
6.1 Informed Consent Process 
Will subjects be required to provide informed consent? 
Yes
No
  
Informed consent will be obtained after either (1) admission to labor and delivery,  (2) 
during an office visit to the obstetrics and gynecology department at Tufts Medical 
Center for regular prenatal care at a date prior to their planned hospital admission, or (3) 
remotely (in accordance with SOP: remote informed consent process HRP-092) if 
consent is not obtained in person by a qualified member of the research team.  For in 
person consent, the consent interview will take place in the subject’s private room at 
Tufts MC after the patient has been seen by the necessary medical teams.  For in person 
consent or remote consent, when the patient is initially approached to participate in the 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 11 of 18 
 
study, the study will be explained and they will have the opportunity to ask any 
questions.  We will explain that their participation in the study does not mean they will 
have a cesarean section, and that study participation will not change their medical care 
during their hospitalization.  We will discuss that even if the patient does not participate 
in the study, she may receive either of the two pain management protocols, depending on 
the preference of the medical team.  We will discuss that their medical history, 
demographic information, and outcomes will be kept confidential on a locked computer.  
Subjects will be asked if they understand the study and that it is voluntary.  Subjects will 
not be pressured to make a decision to participate, and while they will have the option of 
signing consent at the time of the initial interview, or if they would like more time, then a 
member of the research team will check in with the subject the next day. The subject can 
decide not to participate in the study at any time.  The persons obtaining informed 
consent are all medical doctors or research staff from the department of obstetrics and 
gynecology on the study team; however this person may also be the medical doctor in 
charge of the patient’s care as well as a research team member.  
We do anticipate enrolling non-English speaking patients, if they fit our inclusion and 
exclusion criteria. For these patients, the Tufts Medical Center Short Form will be used 
per the Tufts IRB policy.  
7 
 
8 
 
The research will follow SOP: Written Documentation of Consent (HRP-091) and SOP: remote 
informed consent process HRP-092 if consent is not obtained in person. 
8.1 Waiver or Alteration of Consent Process 
 
Is a waiver or alteration of the consent process being requested for this study?  
Yes
No
  
 
Is a waiver of the consent process being requested for parents for research involving children?  
 
Yes
No
  
 
Is a waiver of the consent process for planned emergency research being requested?  
Yes
No
  
8.2 International Research – N/A 
8.3 Confidentiality 
 
The data will be stored in a file on a secured computer in the office of Maternal Fetal Medicine 
Fellows at Tufts Medical Center.  The original ICF’s will also be stored in the office of Maternal 
Fetal Medicine Fellows in a secure storage bin. There will be no specimens stored for the 
research. The data will be stored for seven years after study closure. The PI and other members of 
the research team will have access to the data. The data will be coded using two spreadsheets.  
One spreadsheet will have patient identifying information, as well as a code.  The second 
spreadsheet will have the coded information, along with the data retrieved from the study. Again, 
both spreadsheets will be stored on a password protected computer in a locked office.   
8.4 Provisions to Protect the Privacy Interests of Subjects 
The patients PHI will be kept in a password protected computer in a locked office. 
The patient will be consented in a private room.  The patient’s family may be present.  If the 
patient is consented on L&D, the patient’s nurse may be present as well.   


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 12 of 18 
 
8.5 Provisions to Monitor the Study to Ensure the Safety of Subjects 
 A Data Safety and Monitoring Board is not necessary for this study. If SAEs occur, the 
evaluation will be investigator initiated, and events will be reported to the IRB per the 
IRB’s Reportable New Information policy. The investigator and members of the research 
team will monitor the study through monthly review to ensure the proper reporting of 
SAE’s to the IRB.    
      Reporting timeframe for SAEs and AEs: SAEs and AEs will be reported to the Tufts 
MC/TUHS IRB per the IRB’s Reportable New Information Policy. 
      Accountability procedures as they relate to drugs, devices, and data:  Every effort will 
be made to keep a subject’s data confidential.  Data collected will be maintained on a 
password protected database in a locked office at Tufts MC.  Study data will be kept in a 
locked electronic database for 7 years after the completion of the study and the study is 
closed with the IRB.  
8.6 Compensation for Research-Related Injury 
Does the research involve greater than minimal risk to subjects? 
Yes
No
  
8.7 Economic Burden to Subjects 
Does the research involve any costs to subjects? 
Yes
No
  
 
 
6.10 Vulnerable Populations. 
Will pregnant women be enrolled?   
Yes
No
  
Pregnant women will be enrolled in the study, as the premise of this study is to evaluate 
postpartum pain control.  The study will not alter the course of the subjects’ prenatal care or mode 
of delivery.  If a woman decides to participate in the study, any study interventions will not occur 
until after delivery. This population was chosen for research due to the increased risk of opioid 
misuse among women of childbearing age. The hope is to decrease the amount of opioids 
required while inpatient, and outpatient. Any risk of this research is the least possible for 
achieving the objectives of this study.  
 
There will be no risk to the fetus, or neonate as the medication will not be administered to the subject 
until after delivery.  
Will the research involve neonates of uncertain viability or non-viable neonates?  
Yes
No
  
 
 
Will subjects who are not yet adults (neonates, children, teenagers) be enrolled?  
Yes
No
  
 
Will minors who are:  
i) 
married, widowed, divorced; or  
ii) 
the parent of a child; or  
iii) 
a member of any of the armed forces; or  
iv) 
pregnant or believes herself to be pregnant; or  
v) 
living separate and apart from his/her parent or legal guardian, and is managing 
his/her own financial affairs be approached for study participation for either 
themselves or their child?  


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 13 of 18 
 
 
Yes
No
  
 
Pregnant subjects who are under the age of 18, are considered emancipated minors, persons who 
have not yet attained the age of legal competency as defined by state law, but who are entitled to 
treatment as if they had by virtue of assuming adult responsibilities. They will be deemed capable 
of executing informed consent for this study.  Subjects who are under the age of 18 and are 
pregnant will be evaluated, as for all other potential subjects, for their ability to appreciate the 
risks, benefits, and alternatives for indicated care.  Informed consent will be executed in the same 
way as for other subjects; in a manner that allows for privacy and independent decision making.    
 
 
Will wards of the state and/or children at risk of becoming wards of the state be enrolled (this 
includes foster children or any child that is in state custody)?            
 
Yes
No
  
 
Will cognitively impaired adults (adults with impaired-decision making capacity) or adults who may lose 
the capacity to consent be enrolled?  
Yes
No
  
 
Will prisoners be enrolled?  
Yes
No
  
Will students and/or employees be enrolled in this research?  
Yes
No
 
 
 
9 Adverse Event Monitoring 
9.1 Definitions 
Definition of Serious Adverse Event (SAE) and Adverse Event (AE) for this study: A SAE 
would be one of the following: 
1. results in death; 
2. is life-threatening (places the subject at immediate risk of death from the event as it 
occurred); 
3. requires inpatient hospitalization or prolongation of existing hospitalization; 
4. results in a persistent or significant disability/incapacity; 
5. results in a congenital anomaly/birth defect; or 
6. any other adverse event that, based upon appropriate medical judgment, may jeopardize the 
subject’s health and may require medical or surgical intervention to prevent one of the other 
outcomes listed in this definition (examples of such events include allergic bronchospasm 
requiring intensive treatment in the emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse). 
 
An AE would be any untoward or unfavorable medical occurrence in a human subject, 
including any abnormal sign (for example, abnormal physical exam or laboratory finding), 
symptom, or disease, temporally associated with the subject’s participation in the research, 
whether or not considered related to the subject’s participation in the research..  
 
9.2 Reporting Procedures 
A Data Safety and Monitoring Board is not necessary.  If SAEs occur, the evaluation will be 
investigator initiated, and events will be reported to the IRB per the IRB’s Reportable New 
Information policy.  


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Page 14 of 18 
 
Reporting timeframe for SAEs and AEs: SAEs and AEs will be reported to the Tufts 
MC/TUHS IRB per the IRB’s Reportable New Information Policy. For those SAE’s and 
AE’s not reported to the IRB, these will be identified and managed internally by the research 
team.  SAE and AE’s will be recorded in a database on a password protected computer in a 
locked office. The subject will be treated accordingly and will be counseled regarding the 
events.  
  Accountability procedures as they relate to drugs, devices, and data:  Every effort will be 
made to keep a subject’s data confidential.  Data collected will be maintained on a password 
protected database in a locked office at Tufts MC.  Study data will be kept in a locked 
electronic database for 7 years after the completion of the study and the study is closed with 
the IRB.  
 
9.3 Reportable New Information 
Reportable new information will be reported to the IRB per the Tufts Health Sciences IRB’s 
Reportable New Information policy. 
 
 
10 Statistical Considerations 
10.1 
Study Endpoints 
We expect to see a statistically significant difference in amount of MME’s administered 
between the standard and study protocol arms. The endpoint will be when 71 subjects are 
randomized to each study arm.  The study results will be reported in a peer reviewed journal 
after study completion.  
10.2 
Statistical Analysis 
Demographic and clinical variables will be compared between the two groups to check for 
balance. If it found that confounders are imbalanced between groups, a multivariable linear 
regression model will be performed to adjust for those variables. In addition, if subjects do 
not receive the treatment they were randomized to, a secondary analysis will be performed 
analyzing patients as they were treated. 
All attempts will be made to minimize loss-to-follow-up, and reasons for any missing 
data will be tabulated. Procedures to prevent missing data are described in detail below.  
In addition to evaluating the primary outcome of amount of MME administered, secondary 
analyses will be performed. For secondary analyses, each outcome will be analyzed 
independently, including subject reported pain scores and satisfaction with post-operative 
experience (from phone call survey), estimated blood loss of the surgery and change in pre-
operative to post-operative hematocrit.  
The average morphine milligram equivalents (MME) administered to patients during the post-
operative period after    a cesarean section using the current (standard) protocol is 112.4 
MME, with a standard deviation of 68.7.  The effect size is determined to be a 30% reduction 
in MME in the Ketorolac group, which would be an average of 80 MME. In order to detect at 
30% reduction, with an alpha of 0.05 and a power of 80%, 71 subjects will need to be in each 
group.  
 
Patient noncompliance from the protocol was not anticipated at the time of study 
initiation. Review of blinded interim data showed patient noncompliance with the protocol. 
This interim information was obtained without knowing the allocation of these participants or 
outcome data. With this information, the sample size was adjusted to account for 4% 
noncompliance. 


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a randomized control trial  
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Page 15 of 18 
 
 
Δ=(μ2-μ1) = absolute difference between two means 
σ1,σ2 = variance of mean #1 and #2 
n1 = sample size for group #1 
n2 = sample size for group #2 
α = probability of a type I error (0.05) 
β = probability of a type II error (usually 0.2) 
z = critical Z value for a given α or β 
k = ratio of sample size for group #2 to group #1 
 
Inflated Sample Size = Required Sample Size/(1 - noncompliance percent) = 142/(1-0.04) = 
142/(0.96) = 147.9.7 = 148 patients. 
 
10.3 
Number of Subjects 
All of the subjects of this study will be enrolled at Tufts Medical Center.  Per the power 
calculation as above, 71 subjects will be enrolled in each arm. Anticipating patient 
noncompliance or withdrawal from the protocol, 74 patients will be enrolled in each arm. 
Up to 500 subjects will be enrolled in order to have 148 subjects complete the study.  
10.4 
Data Management 
Data with patient demographic and operative information will be recorded on a paper 
form during the cesarean delivery, and placed in a locked box at the end of the case. 
Forms will be collected and inputted into a password protected data set which will be on 
a Tufts Medical Center computer in a locked office and the forms will be stored in a 
locked office. Clinical data from the hospital admission and phone calls will be recorded 
in the electronic medical record, which requires a username and password to access.  
Data will be abstracted from the electronic medical record and inputted into the locked 
spreadsheet.  
The data will be collected from the electronic medical records system and from the phone 
call 2 weeks postpartum.  The data collected will include the number of doses of opiate 
medications administered during the postpartum period, as well as the pain scores.  The 
phone call will consist of a series of multiple choice questions.  All data will be recorded 
and entered into a secured, de-identified Excel spreadsheet, which is kept on a password 
protected computer in a locked office. The data will be stored for 7 years after the 
completion of the study.  


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 16 of 18 
 
Certificate of Confidentiality: Not applicable 
 
Parties who will have access to the data, including the key to the identity code: 
Michael House MD, Jean Hostage MD, Members of the investigational drug pharmacy at 
Tufts Medical Center.   
 
Parties who will have access to research records:  
Michael House MD, Jean Hostage MD, Members of the investigational drug pharmacy at 
Tufts Medical Center 
 
10.5 
Randomization 
Will subjects be randomized?  
Yes
No
  
At the time of skin closure, participants will be randomized to receive either the standard 
or study protocol using a digital randomization sequence generator based on randomly 
permuted blocks of 4. Based on this sequence, the IDS pharmacy will assign the subject 
to either the study or standard group.  The subjects, care providers and investigators will 
be blinded to the group assignment.  
 
 
11 Drugs or Devices 
Will the research involve drugs?   
Yes
No
  
Will the research involve devices?   
Yes
No
  
If Yes to either, describe the following: 
This research involves Ketorolac, which is a drug that is already commonly used on the Labor 
and Delivery and Mother-Infant unit of Tufts Medical Center.   The investigational drug 
pharmacy will be accountable for the drugs.  
A computerized order set (see example in section 5.2), will be used for this research.  The 
Ob/Gyn residents, fellows and attendings will use this order set after randomization of subjects to 
each group.  A paper order form created by the IDS pharmacy will also be completed and sent to 
the IDS pharmacy in order to prepare the standard or study syringes.  The anesthesiologists will 
administer the first dose of Ketorolac in the operating room.  Nurses on Labor and Delivery and 
the Mother-Infant Unit will administer subsequent doses of Ketorolac or placebo, as well as any 
other medications ordered by the physician teams.  This is within the scope of the nurses’ typical 
job duties.   
12  Study Administration 
12.1 Setting 
The study will be conducted at Tufts Medical Center, 800 Washington Street, Boston MA 
02111.  Records will be kept on a locked spreadsheet on a computer in a locked office at 
Tufts Medical Center.  The record operating room information will be used to input data 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 17 of 18 
 
into the spreadsheet and then stored in a locked office.  Study participation will not 
require an increase in the length of hospital stay. 
12.2 Registration 
Patients will be designated a study participant when they sign the informed consent 
document.  Subjects will be randomized to either study arm at the time of skin closure 
when they undergo cesarean delivery.  Not all patients will be randomized or included in 
the analysis as not all patients who sign an informed consent will have a cesarean 
delivery. 
12.3 Resources Available 
The primary investigator and Co-Investigators will be responsible for conducting the 
study.  The PI and other members of the research team will be responsible for consenting 
patients, organizing and analyzing data and for communicating with study participants.   
Study personnel will not always be present during randomization and medication 
administration. 
All members of the study team are physicians and have completed CITI training.  
Any subject safety issues that occur while the PI is away or unavailable can be addressed by the 
on call supervising physician. 
Our research team will be able to feasibly recruit the required number of suitable subjects within 
the proposed recruitment period. We will have access to at least 100 potential subjects per month 
(as estimated by the average number of deliveries at Tufts Medical Center each month), with 
about 40 of these subjects undergoing cesarean section (as estimated by the 40% cesarean section 
rate at Tufts Medical Center).    
12.4 IRB Review 
An appropriate IRB registered with the OHRP, will review and approve this study. Any amendments to 
the protocol or informed consent documents will be reviewed and approved by the IRB prior to use, 
unless required to eliminate an apparent immediate hazard to subjects.    
12.5 Multi-Site Research 
Is this a multi-site study where Tufts is the sponsor, primary grant recipient, or coordinating site?: 
Yes
No
  
 
12.6 Community-Based Participatory Research 
Will this study involve community-based participatory research?  
Yes
No
  
12.7 Sharing Results with Subjects  
Will results (overall study results or individual subject results, such as results of investigational diagnostic 
tests, genetic tests, or incidental findings) be shared with subjects or others (e.g., the subject’s primary 
care physician or the subject’s treating physician)?   
Yes
No
  
13 References 
1.  
Postpartum pain management. ACOG Committee Opinion No. 742. American College of Obstetricians and 
Gynecologists. Obstet Gynecol 2018:132. DOI: 10.1097/AOG.0000000000002683. Epub 2018 May 18. 


PROTOCOL TITLE: Scheduled Ketorolac administration after cesarean section and its effect on opioid use: 
a randomized control trial  
VERSION DATE: 2/15/22 
 
 
Page 18 of 18 
 
2.  
Lucas DN, Gough KL. Enhanced recovery in obstetrics – a new frontier? Int J Obstet Anesth. 
2013;22(2):92-95. doi:10.1016/j.ijoa.2013.02.001 
3.  
Kolettis D, Pombar X, Perry P, Butts E. Reduction in Narcotic Analgesic Use on Labor and Delivery Unit: 
Examining the effects of institutional policy. 
4.  
World Health Organization.  Cancer pain relief.  Geneva: WHO; 1986. Available at 
http://apps.who.int/iris/bitstream/handle/10665/43944/9241561009_eng.pdf. Retreived Sept 7, 2018. 
5.  
Todd, Knox H, et al. Clinical Significance of Reported Changes in Pain Severity. Ann Emerg Med. 
1996;27(4):485-489. 
6.  
Frank R. The Opioid Epidemic and The Secretary’s Opioid Iniative US Department of Health and Human 
Services 2016. 
7.  
Beaver W. Ketorolac tromethamine: an introduction. Pharmacotherapy. 1990;(10):29S. 
8.  
Parker R. Use of ketorolac after lower abdominal surgery. Anesthesiology. 1994;(80):6-12. 
9.  
Gillies G. The morphine sparing effecty of ketorolac tromethamine. Anaesthesia. 1987;42:727-731. 
10.  Vadivelu N. Ketorolac, Oxymorphone, Tapentadol, and Tramadol: A Comprehensive Review. Anesthesiol 
Clin. 2017;35(2):e1-e20. 
11.  Lowder J, Shackelford D. A randomized, controlled trial to compare ketorolac tromethamine versus placebo 
after cesarean section to reduce pain and carcotic usage. Am J Obstet Gynecol. 2003;December(189):1559-
1562. doi:10.1016/j.ajog.2003.08.014 
12.  Gobble RM, et al. Ketorolac Does Not Increase Perioperative Bleeding: A Meta-Analysis of Randomized 
Controlled Trials. Plast Reconstr Surg. 2014;133(3):741-755. 
13.  Viteri O, et al. Association of Nonsteroidal Antiinflammatory Drugs and Postpartum Hypertension in 
Women With Preeclampsia With Severe Features. Obstet Gynecol. 2017;130(4):830-835. 
14.  Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical 
implications. Am J Med. 1999;106(5):13s-24s. 
15.  Calculating the total daily dose of opioids for a safer dosage CDC.gov. 
 
 
 

ICF_001.pdf: 
Scheduled Ketorolac administration after cesarean section and its effect on opioid consumption: a randomized 
control trial 
Michael House, MD.  
         
ICF version:  9/14/2021 
Page 1 of 9 
 
STUDY TITLE: 
Scheduled Ketorolac administration after cesarean section and its effect on opioid use: a 
randomized control trial 
 
 
PRINCIPAL INVESTIGATOR 
Name:  Michael House, MD 
Department Obstetrics and Gynecology, Division of Maternal Fetal Medicine 
Telephone Number: 617-636-4549 
Email Address mhouse@tuftsmedicalcenter.org 
NCT03678675 
 
 
 


Scheduled Ketorolac administration after cesarean section and its effect on opioid consumption: a randomized 
control trial 
Michael House, MD.  
         
ICF version:  9/14/2021 
Page 2 of 9 
 
TUFTS MEDICAL CENTER 
TUFTS UNIVERSITY 
Department of Obstetrics and Gynecology 
 
INFORMED CONSENT TO PARTICIPATE IN RESEARCH 
 
Scheduled Ketorolac administration after cesarean section and its effect on opioid consumption: 
a randomized control trial 
 
Principal Investigator: Mohak Mhatre, MD 
Co-Investigators: Jean Hostage, MD 
Study team telephone number: 617-636-4549  
 
Key Information: The following is a short summary of this study to help you decide whether 
or not to be a part of this study. More detailed information is listed later on in this form. 
 
Why am I being invited to take part in a research study? 
We invite you to take part in a research study because it is a study involving the best way to 
control pain after a cesarean section while in the hospital, and you may have a cesarean delivery. 
 
What should I know about a research study? 
 Someone will explain this research study to you. 
 Please also read all of the following information carefully. 
 Whether or not you take part is up to you. 
 You can choose not to take part. 
 You can decide to take part and later change your mind. 
 Your decision will not be held against you. 
 You can ask all the questions you want before you decide. Do not sign unless you 
understand the information in it and have had your questions answered to your 
satisfaction.   
 
PURPOSE OF STUDY 
 
The purpose of this study is to determine if a pain medication plan can help reduce the amount of 
opiate medication needed to control pain after cesarean sections.  Ketorolac is an FDA approved 
anti-inflammatory medication similar to Ibuprofen. It is already used commonly for standard of 
care to control pain after cesarean sections and many other types of surgeries on an “as needed” 
basis. Our goal is to see if scheduled doses of Ketorolac given every 6 hours for the first 24 hours 
after surgery will improve pain control and decrease the need for opiate medications.  It is 
possible that the scheduled doses may decrease the need for opiate medications.  But it is also 
possible that this new plan will have no effect or even increase the need for opiate medications.   
 
The study will be conducted at Tufts Medical Center, 800 Washington Street, Boston MA 02111 
on Labor and Delivery.  500 subjects will be enrolled however not all of these subjects will have 


Scheduled Ketorolac administration after cesarean section and its effect on opioid consumption: a randomized 
control trial 
Michael House, MD.  
         
ICF version:  9/14/2021 
Page 3 of 9 
 
a cesarean delivery.  We plan to randomly assign 148 subjects to either the standard plan for pain 
control or a study plan for pain control. If you participate in this study, you may have access to 
the study drug if you require it during future hospitalizations.  However, this drug is not available 
as a home medication. 
 
PROCEDURES TO BE FOLLOWED 
 
If you have a cesarean delivery and decide to be part of this study, the pain medication plan you 
get will be chosen by chance. Neither you nor the study doctor will choose what plan you get.  
You will have a 50% chance of being part of the study plan and 50% chance of being part of the 
standard plan.  The decision for standard or study plan will be made randomly like a coin flip. 
Neither you nor the study doctor will know which pain medication plan you are getting. Whether 
you are assigned to the study or standard plan, your pain will be assessed and treated 
appropriately as part of your regular standard of care.  Standard of care includes using 
acetaminophen (Tylenol) or opioid medications to control pain.   
 
All subjects regardless of which pain control plan they are assigned to, will receive one dose of 
Ketorolac before leaving the Operating Room. 
 
If you are randomized to receive the standard plan you will receive up to two (2) doses of 
Ketorolac after your cesarean section.  This is the current pain control plan at Tufts Medical 
Center.  If you are part of the standard group, you will also receive four (4) doses of a placebo, or 
inactive drug. This will consist of only normal saline, or salt water.  
 
If you are randomized to receive the study plan you will receive a scheduled five (5) doses of 
Ketorolac after your cesarean section.  Regardless of which group you are assigned to, you will 
receive your first dost of pain medication (Ketorolac) before leaving the operating room.  
 
For both plans, you will also need to have an intravenous catheter (an “IV”) in place for the first 
36 hours after leaving the operating room.  Typically, the IV is removed about 12 hours after a 
patient leaves the operating room. For both plans, per standard of care, blood samples will be 
collected to measure your blood count on the days after the cesarean section.  At this time, your 
kidney function will also be evaluated by evaluating that blood sample.  
 
For both plans, you will also be evaluated throughout your time in the hospital as you normally 
would. To measure how well your pain is controlled and the amount of opiate medications you 
needed in the hospital, your medical records will be reviewed, as will notes from a follow up 
phone conversation after you leave the hospital.  You will receive a phone call and be asked a 
series of 9 questions about your stay in the hospital at about 2 weeks after you are discharged 
from the hospital.  The phone call should take less than 10 minutes of your time.  If you do not 
answer, we will leave a voicemail and try to reach you a second time. The total time of 
participation in the study will be 2 weeks. Per normal obstetric care, you will have a 2 week 
wound check visit and a 6 week postpartum visit.  For these visits you can follow up with an 
obstetrician at Tufts Medical Center or your primary obstetrician, and this may not be at Tufts 
Medical Center. Six weeks after delivery is the usual period of time that women are followed 


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Michael House, MD.  
         
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after having a baby. None of the information gathered at the six week check-up will be used for 
research.   If you have any additional concerns about your pain control outside of these outlined 
evaluations, you can call the Maternal Fetal Medicine clinic at Tufts Medical Center (617-636-
4549) and an appointment will be arranged.   
 
Your information that is collected as part of this research will not be used or 
distributed for future research studies, even if all of your identifiers are removed. 
 
Even if you decide not to participate in the study, you could still receive either one of the pain 
control plans. Your regular doctor would decide what kind of pain medication plan you receive.   
 
RISKS 
 
Women undergoing cesarean section will have some degree of pain or discomfort.   Other risks 
of the procedure include discomfort from placing or maintaining the IV catheter and any side 
effects from Ketorolac. Side effects may be more likely to occur in the repeated doses in the 
study plan. Side effects of ketorolac are rare, but can potentially include headache, upset 
stomach, nausea, vomiting, risk for bleeding stomach ulcers, kidney injury, excessive bleeding, 
blood clots in your legs, lungs brain or heart, including heart attack, heart failure, high blood 
pressure, skin reactions, effects on liver function, low blood count and serious allergic reactions. 
Extra precautions will be taken in patients who have a history of asthma, as Ketorolac can trigger 
an asthma attack.  Available information has not shown any specific adverse events (side effects) 
in nursing infants; however, please contact the study doctor right away if you notice any. 
 
Normally, the standard of care at Tufts Medical Center, for subjects like you who would benefit 
equally from both study plans, would involve a conversation between you and the doctor about 
the best pain medication plan. The decision to choose a pain medication plan may depend on 
your medical history]or the personal preference of the doctor. Participating in this study is 
different from the standard of care because neither the patient nor the doctor gets to choose the 
pain medication plan. You will be randomly assigned to the standard plan or the study plan. 
 
Loss of confidentiality is a risk of study participation.  However, data collected from this study 
will be stored on a locked spreadsheet on a computer in a locked office at Tufts Medical Center 
so the risk of loss of confidentiality is low.  Paper records will be stored in a locked office at 
Tufts MC.   
 
BENEFITS 
 
There are no direct benefits to you from participating in this study if you are randomized to 
receive the standard plan.  If you are randomized to the study group, there is a potential benefit 
of less narcotic use and better pain control after your delivery.  Potential benefits of less narcotic 
use include; less constipation and sedation, leading to improved pain control and possibly shorter 
hospital stay..  However, data collected for this study may contribute to the knowledge of post-
operative pain control and women in the future may benefit from what is learned.  
 


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Michael House, MD.  
         
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ALTERNATIVES 
 
The alternative is to NOT participate in the research study. Your medical care during your 
hospitalization will not change if you do not participate.  If you chose not to participate, then you 
could receive either the standard plan or study plan depending on the preference of your 
attending surgeon. 
 
Detailed Information: The following is more detailed information about this study in 
addition to the information listed above. 
 
WITHDRAWAL 
 
If you are eligible to participate and decide to be in the study, the Principal Investigator may still 
choose to stop your participation in this study if he thinks it is in your best medical interest.   
You will not be included in the study if you have a cesarean delivery but are not assigned to 
either study arm while in the operating room.   
 
You can also leave the research at any time it will not be held against you.  If you refuse to 
participate in the study or stop being in this study, it will not affect your care or treatment outside 
this study, payment for your health care, or your health care benefits.  
 
We will tell you about any new information that may affect your health, welfare, or choice to 
stay in the research. 
 
If you withdraw or are withdrawn from the study, any data collected from you before your 
withdrawal will still be used for the study. 
 
If you stop being in the research, already collected data may not be removed from the study 
database. You will be asked whether the investigator can collect data from your routine medical 
care.  If you agree, this data will be handled the same as research data. 
 
RESEARCH RELATED INJURY 
 
Emergency medical treatment will be given to you if you are hurt or get sick as a direct result of 
being in this research study. You or your insurance carrier will be required to pay for any such 
medical care. Any needed medical care is available at the usual cost. All needed facilities, 
emergency treatment, and professional services are available to you, just as they are to the 
general public. The institution will not pay for your treatment if you become ill or injured as part 
of this study.  
 
COSTS 
 


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There are no additional costs associated with this study. The cost of your usual standard of care 
will continue to be your responsibility or that of your insurance.  At this time, the hospital does 
not bill patients separately for the pain medications used after cesarean delivery.  
 
You and/or your insurance plan will need to pay for the costs of medical care you get as part of 
the study, just as you would if you were getting the usual care for your condition.  This includes: 
 
 The costs of tests, exams, procedures, and drugs that you get during the study to monitor 
your safety, and prevent and treat side effects.   
 The costs of getting the ready Ketorolac and giving it to you.  
 Your insurance co-pays and deductibles. 
 
PAYMENT 
 
You will not be paid for participating in this study. 
 
PRIVACY AND CONFIDENTIALITY 
 
Research data and medical information will be stored in password protected documents on a 
Tufts MC computer in a locked office. Paper records will also be stored in a locked office at 
Tufts MC.  For analysis, your file will be assigned a code that is only accessible to members of 
the research team.   
 
If you decide to take part in this research study, your personal information will not be given to 
anyone unless we receive your permission in writing. It will only be given if the law requires it. 
It will also only be given for regular hospital treatment, payment, and hospital management 
activities.  
 
We will make every effort to keep your information private, but it cannot be completely 
guaranteed. The Institutional Review Board of Tufts Medical Center and Tufts University Health 
Sciences may check records that identify you. This might include your medical or research 
records and the informed consent form you signed. The records of this study might also be 
reviewed to make sure all rules and guidelines were followed. 
 
We may publish the results of this research. However, we will keep your name and other 
identifying information confidential. 
 
A description of this clinical trial will be available on http://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. 
 
AUTHORIZATION TO USE OR DISCLOSE YOUR IDENTIFIABLE HEALTH 
INFORMATION  
 


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If you sign this document, you give permission to the Principal Investigator named above and 
research staff at Tufts Medical Center as well as other individuals at Tufts Medical Center who 
may need to access your information to do their jobs (such as for treatment, payment (billing) or 
health care operations) to use or disclose (release) your health information that identifies you for 
the research study described above.   
 
The parties listed in the preceding paragraph may disclose the health information described 
below to the following persons and organizations for their use in connection with the research 
study:  
 Individuals or organizations working under the direction of the Principal Investigator(s) 
for the study,  
 Outside individuals or entities that have a need to access this information to perform 
activities relating to the conduct of this research, such as analysis by outside laboratories 
on behalf of Tufts Medical Center, 
 Other researchers and institutions that are conducting or participating in this study,  
 The Office for Human Research Protections in the U.S. Department of Health and 
Human Services, the United States Food and Drug Administration (FDA) and other 
federal and state agencies that have the right to use the information as required by law, 
and 
 The members and staff of any Institutional Review Board (IRB) that oversee this study. 
 
The health information that we may use or disclose (release) for this research study includes all 
information in your medical record related to the diagnosis and management of your 
postoperative course, including the record of your care, as well as any information collected or 
created during the course of this study. 
 
Tufts Medical Center is required by law to protect your health information. By signing this 
document, you authorize Tufts Medical Center to use and/or disclose (release) your health 
information for this research. Those persons who receive your health information may not be 
required by Federal privacy laws (such as the Privacy Rule) to protect it and may share your 
information with others without your permission, if permitted by laws governing them. You may 
not be allowed to see or copy the information described on this form as long as the research is in 
progress, but you have a right to see and copy the information upon completion of the research in 
accordance with hospital policies. 
 
Tufts Medical Center may not withhold or refuse to provide you with clinical care based on 
whether or not you sign this form.  
 
This authorization does not have an expiration date. You may change your mind and revoke 
(take back) this authorization at any time. Even if you revoke this authorization, this site’s 
clinical, administrative and research staff may still use or disclose health information they 
already have obtained about you as necessary to maintain the integrity or reliability of the current 
research. To revoke this authorization, you must write to: HIPAA Privacy Officer for Research, 


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800 Washington Street, Box 5100, Boston, MA 02111. If you revoke this authorization, you may 
no longer be allowed to participate in the research described in this form.  
 
WHOM TO CONTACT 
 
If you have questions, concerns, or complaints, or think the research has hurt you, talk to the 
research team at:  
 
Mohak Mhatre, MD,  mmhatre@tuftsmedicalcenter.org , 617-636-4549 (Day)  
Jean Hostage, MD jhostage@tuftsmedicalcenter.org, 617-636-4549 (Day) 617-636-4250 
(evening)  
 
If you have question about your rights as a research study subject, call the Tufts Medical Center 
and Tufts University Health Sciences Institutional Review Board (IRB) at (617) 636-7512. The 
IRB is a group of doctors, nurses, and non-medical people who review human research studies 
for safety and protection of people who take part in the studies. Federal law requires the IRB to 
review and approve any research study involving humans. This must be done before the study 
can begin. The study is also reviewed on a regular basis while it is in progress. This research 
study has been reviewed and approved by the IRB of Tufts Medical Center and Tufts University 
Health Sciences. 
 
 


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Documentation of Consent 
 
I have been given a copy of this form. I have read it or it has been read to me. I understand the 
information and have had my questions answered to my satisfaction. I agree to take part in this 
study.  
 
I understand that I will be informed of any new findings developed during the course of this 
research study that may affect my willingness to stay in this research study. 
 
 
_________________________________________        ___________  
  __________  
Participant’s Signature 
 
 
 
       Date 
 
  Time (required for  
 
 
 
 
 
 
 
 
 
 
  all clinical trials at   
 
 
 
 
 
 
 
 
 
 
  Tufts Medical Center) 
 
I have fully explained to ________________________________ the nature and purpose of the 
above-described study and the risks that are involved in its performance.  I have answered all 
questions to the best of my ability. 
 
 
_____________ 
 
 
____________________________________________ 
Date 
 
 
 
 
Principal Investigator or Representative’s Signature 
 
 
Witness Signature: 
 
 
_________________________________________        ___________  
  __________  
Witness’ Signature 
 
 
 
        
        Date 
 
  Time (required for  
 
 
 
 
 
 
 
 
 
 
  all clinical trials at   
 
 
 
 
 
 
 
 
 
 
  Tufts Medical Center) 
_________________________________________ 
Witness Printed Name