Prophylactic Analgesic and Antiemetic Regimen for Medical Abortion < 70 Days
Phase: EARLY_PHASE1
Conditions: Nausea, Pain
Sponsor: Hackensack Meridian Health

CLINICAL STUDY PROTOCOL 
FOR DRUG/DEVICE/BIOLOGIC RESEARCH 
 
 
 
Prophylactic Analgesic and Antiemetic Regimen for Medical 
Abortion < 70 days 
 
Version 5 
1/20/2023 
 
 
 
 
 
 

 
Study Number  
Date of current version - version DRAFT
 
Study Personnel 
 
PI: Melissa Figueroa, MD 
Department of Family Planning 
Contact information  
Sub-I(s):  
Amna Iftikhar, MD Department of Obstetrics and Gynecology 
Antonia Francis Kim, MD Department of Maternal Fetal Medicine 
 
Name and information of sponsor: Hackensack Meridian Health
 
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Study Number  
Date of current version - version DRAFT
 
Protocol Amendment History 
 
Version 
Date 
Description 
Original version 
4/1/22 
Original submission 
2 
9/17/22 
Edits made as requested by IRB 
3 
11/19/22 
Edits made as requested by IRB: 
- Clarification on informed consent process 
(section 9.7) 
- Clarification on when the patient’s medical 
information will be collected and stored in red cap 
(section 6.1 and 6.6) 
- Length of time patient’s records will be stored in 
encrypted redcap changed from 6 years to 2 
years 
4 
12/28/22 
Addendum of section 9 as per request by IRB. 
HIPAA alteration statement removed from 
proposal. 
5 
1/20/23 
-​
Clarification on recruitment of study 
(section 6.3) 
-​
Time frame of study changed given IRB 
approval not yet obtained (section 4.1.1) 
 
 
 
 
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Study Number  
Date of current version - version DRAFT
 
Summary  
Study Description 
Randomized trial which will aim to evaluate whether 
prophylactic use of ondansetron and ibuprofen will 
decrease side effects associated with medical 
abortion and increase patient satisfaction 
Objectives 
- Determine if prophylactic use of ondansetron and 
ibuprofen during medical abortion treatment can 
increase patient satisfaction thereby creating a 
more favorable outcome 
- Evaluate for ideal pain and anti-nausea 
management regimen for medical abortion 
 
Endpoints/variables 
- Nausea and pain scale at 6-8hour mark and 24 
hour mark after administration of misoprostol 
- Patient report of satisfaction with the experience 
and likelihood to recommend a similar regimen to 
others 
Study Population 
Healthy, English speaking 18-50 year old female 
volunteers undergoing medical abortion whether for 
voluntary interruption of pregnancy or missed 
abortion 
Phase 
n/a. the medications given in this study are part of 
the standard of care when treating side effects of 
medical abortion.  
Description of sites 
(facilities enrolling 
patients) 
HUMC OBGYN Faculty Practice 
Study duration 
March 2023- November 2023 
Participant duration 
2-3 weeks (includes follow up appointment) 
Schedule of activities 
- Subjects seen in office and enrolled in study 
- Subjects take misoprostol 24 hours after taking 
mifeprex and will either take ibuprofen and 
ondansetron prophylactically or not 
- Subjects will record their pain and nausea score at 
the 6-8 hour mark and the 24 hr mark 
- Subjects will return to the office for follow up  
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Study Number  
Date of current version - version DRAFT
 
Follow up / End of study 
definition  
Each patient will have a follow up visit 2 weeks after 
participation to discuss their experience 
End of study: after 168 subjects have be enrolled or 
at end of November 2023 
 
 
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Date of current version - version DRAFT
 
1 – Introduction    
There is currently an ACOG recommended regimen for successful medical abortion 
however there is no official recommendation for management of associated side 
effects related to this process. The use of analgesic medications including ibuprofen 
and antiemetics including ondansetron are common in the management of said side 
effects. Our study aims to determine if prophylactic use of ondansetron and 
ibuprofen during medical abortion treatment can increase patient satisfaction thereby 
creating a more favorable outcome 
 
2 – Background 
The recommended regimen for medical abortion up to 70 days GA is 200mg 
of oral mifepristone followed by 800mcg of misoprostol administered either buccally, 
vaginally, or sublingually. While the efficacy of medical abortion is greater than 90%, 
there are considerable unpleasant side effects associated with these agents (1). 
Patients often consider these potential side effects when electing for medical vs 
surgical management for medical abortion (2). Nausea, vomiting and pain are 
common side effects of misoprostol, particularly when taken orally (3). The most 
severe pain is reported to occur about 2.5-4hrs after misoprostol use, lasting about 1 
hour in duration (4). 
While there is a recommended regimen for successful medical abortion, there is no 
official recommendation for management of the above associated side effects. 
According to the WHO, research is needed to evaluate the ideal pain management 
regimen for medical abortion, including additional medications and timing of 
medication administration (5). Livshits et al found that ibuprofen is more effective 
than acetaminophen to reduce pain (6). Ibuprofen is commonly taken as therapeutic 
management for pain rather than prophylactically to prevent or decrease the intensity 
of pain experienced during medical abortion. Prior studies have assessed 
pre-emptive analgesia in the setting of medication abortion. Avraham et al found that 
pre-emptive ibuprofen treatment was found to be more effective than a placebo in 
pain prevention (7). Dragoman et al also investigated preemptive pain control 
administration with tramadol or ibuprofen/metoclopramide and found lower mean 
maximum pain scores in both experimental groups compared to placebo. 
Nonetheless, the lower mean maximum pain scores did not achieve clinical 
significance (8). Despite these findings, they concluded that ibuprofen, tramadol, and 
metoclopramide should be considered for prophylactic pain management in medical 
abortions.  
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Ondansetron is another antiemetic that has been shown to be more effective 
than metoclopramide when managing postoperative nausea after laparoscopic 
cholecystectomy as well as chemotherapy induced nausea and vomiting (9,10). We 
hypothesize that prophylactic use of ondansetron and ibuprofen will increase overall 
patient satisfaction and decrease mean pain and nausea scores during the medical 
abortion process.  
 
3 – Rationale, Objectives and Hypothesis  
3.1. Study Rationale/Problem Statement/Research question or Study 
significance 
Determine if prophylactic use of ondansetron and ibuprofen during medical abortion 
treatment can increase patient satisfaction thereby creating a more favorable 
outcome 
3.2. Hypothesis (if applicable) 
The prophylactic use of ondansetron and ibuprofen will increase patient satisfaction 
during medical abortion treatment 
3.3. Primary Objective 
Determine if prophylactic use of ondansetron and ibuprofen during medical abortion 
treatment can increase patient satisfaction thereby creating a more favorable 
outcome 
3.4. Primary Outcome Variable(s) 
Patient satisfaction rating (see below for rating tool) 
3.5. Secondary Objective(s) (if applicable)  
Evaluate for a satisfactory pain and anti-nausea management regimen for medical 
abortion 
3.6. Secondary Outcome Variable(s) (if applicable) 
Maximum pain and nausea score in first 24 hours, need for additional 
anti-emetics/analgesics  
 
4 - Study Design 
4.1 General Design 
This study is a randomized trial which will involve tow study groups. One group will 
be the intervention group which will be asked to take ibuprofen and ondansetron at 
the time of misoprostol administration. The second group will be the control group 
which will be asked to take ibuprofen or ondansetron only when experiencing pain or 
nausea respectively. 
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Study Number  
Date of current version - version DRAFT
 
4.1.1 Study Duration  
Data collection will take place from March 2023 to November 2023 
Data will be analyzed from March 2023 to November 2023 
4.1.2 Participant duration  
Approximately 2 weeks 
4.1.3 Number of Study Sites 
Hackensack University Medical Center  
5 – Study population  
5.1. General description  
●​ Healthy, English speaking 18-50 year old female volunteers undergoing 
medical abortion whether for voluntary interruption of pregnancy or missed 
abortion 
5.2. Number of Participants 
o​ 168 total based on power analysis: Two independent study groups, 
continuous, group 1 mean 7 (+/- 3), group 2 mean 5.5, alpha 0.05, power 0.9 
 
5.3. Eligibility Criteria 
●​ Inclusion criteria: Healthy, English speaking 18-50 year old female volunteers 
undergoing medical abortion whether for voluntary interruption of pregnancy 
or missed abortion 
o​ GA </= 70 days confirmed via ultrasound 
o​ Access to a time keeping device 
o​ Willingness to complete a telephone or in-clinic follow up 
●​ Exclusion criteria: chronic medical problems including but not limited to 
cardiac conditions, malignancy or organ damage  
o​ Failed medical abortion resulting in surgical management 
o​ Known intrauterine infection 
o​ Known allergy to ondansetron or ibuprofen 
o​ Subjects chronically receiving analgesic drugs 
o​ Subjects unable to give consent 
o​ Subjects taking medications that interact with ondansetron or ibuprofen 
5.3.1. Pregnancy, Breastfeeding and Contraception requirements (if 
applicable): see above 
5.3.2. Vulnerable populations (if applicable): not applicable 
5.3.3. Withdrawal criteria (as applicable) 
Patient who fail medical management and need surgical management. These 
patients will be withdrawn from the study and replaced. 
 
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6 – Study intervention (drug/device/biologic) 
6.1. General description 
●​ Eligible patients seeking medical abortion treatment during appointments with 
a family planning specialist will be verbally given information about the study. 
Those who express interest will undergo a detailed informed consent 
process.  
●​ Consent and counseling will be available in English only 
●​ Counseling on medication abortion for each patient will be standardized. Each 
patient will be provided instructions to go home with 
●​ Randomized controlled trial 
o​ Randomly assign treatments in a 1:1 ratio.  
o​ Patients will be given mifepristone in the clinic 
o​ Will be given 800mcg of misoprostol and instructed to insert vaginally.  
o​ The intervention group will be instructed to take ibuprofen and 
ondansetron with the misoprostol as a prophylactic measure 
o​ The control group will be instructed to take ibuprofen or ondansetron 
only when experiencing pain or nausea respectively 
●​ Information on the patients demographics (age, race, ethnicity, gravity and 
parity, obstetrical history, BMI) will be recorded as well as gestational age at 
time of administration and diagnosis (missed abortion vs elective termination 
of pregnancy). This will be recorded and kept in the encrypted RedCap 
system after patient agrees to participate in the study.  
●​ Subjects will also be asked their mean pain score on a numerical pain scale of 
1-10 during their menstrual cycles as well as need for analgesia during 
menstruation. 
●​ Subjects will be asked if they are experiencing nausea or vomiting prior to 
starting the study. They will also be asked if they have a history of bariatric 
surgery, baseline reflux, conditions that can predispose them to 
nausea/vomiting 
●​ Subjects will be asked to record their nausea and pain level using a numerical 
scale rating at the 6-8 hour mark after administration of misoprostol. After 24 
hours of administration, they will be asked their maximum pain score over the 
course of the first 24 hours. The subjects will have the option to either record 
their pain scores in a log or to text their pain scores directly to a designated 
phone number. Contact via text message will be encouraged as this will allow 
for live feedback and reduce recall bias 
●​ Researchers will contact participants 3-5 days thereafter to collect and/or 
verify information on their pain and nausea scales and determine adherence 
to treatment regimen. They will also collect information on supplemental 
analgesia and antiemetics that may have been used. 
●​ Subjects will be asked how satisfied they were with their overall experience 
(Very satisfied/Fairly satisfied/Neither satisfied nor dissatisfied/Fairly 
dissatisfied/Very dissatisfied). They will also be asked how likely they are to 
recommend this pain/antiemetic regimen method to a friend (Extremely 
likely/Likely/Neither likely nor unlikely/Unlikely/Extremely unlikely /Don’t 
know). 
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●​ Ask the patient to return for follow up visit to determine abortion status. 
o​ Information on successful abortion will also be collected at the follow 
up visit 
6.2. Screening and screen failures: not applicable 
6.3. Recruitment, enrollment and retention (including screen failures as applicable) 
Eligible patients seeking medical abortion treatment during appointments with a 
family planning specialist will be verbally given information about the study by the 
provider. Those who express interest will undergo a detailed informed consent 
process.  
6.4. Study intervention 
6.4.1 Dosing and Administration: 
Intervention arm: patients will be instructed to take the ibuprofen 600mg and 
ondansetron 4mg at the time of misoprostol administration. The ondansetron dose is 
the minimum amount that can be administered at a given time. The ibuprofen dose is 
the standard recommended in our office currently for pain management for patients 
ungoing medical abortion. 
No intervention arm: patients will be instructed to take misoprostol and take 600mg 
of ibuprofen for pain as need or ondansetron 4mg as needed for nausea 
6.4.2. Dose modification (if applicable): patients will be instructed on the 
appropriate time interval in which they can take additional medication for pain or 
nausea  if required 
6.4.3. Schedule of events (schema) 
- Subjects seen in office and enrolled in study (clinical visit) 
- Subjects take misoprostol 24 hours after taking mifeprex and will either take 
ibuprofen and ondansetron prophylactically or not 
- Subjects will record their pain and nausea score at the 6-8hr mark and the 24hr 
mark 
- Subjects will return to the office for follow up (clinical visit) 
6.4.4. Study visits (only if study has multiple visits, explain what will happen in 
each visit, dosing, assessments etc.) 
1. First visit: patient will be seen in the office for medical management of missed 
abortion. The treatment will be explained to them as well as the study itself and 
instructions on how to take medication to manage side effects. Will be instructed to 
take the medication prophylactically vs when in pain 
2. Follow up visit after medical abortion to determine if abortion was successful as 
well as to discuss the overall experience  
6.5. Assignment / randomization (if applicable): patient will be randomly assigned 
on a 1:1 ratio using a random number generator 
6.6. Data collection (data points, source and storage) 
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●​ Information on the patients demographics (age, race, ethnicity, gravity and 
parity, obstetrical history, BMI) will be recorded as well as gestational age at 
time of administration and diagnosis (missed abortion vs elective termination 
of pregnancy) 
●​ Subjects will also be asked their mean pain score on a numerical pain scale of 
1-10 during their menstrual cycles as well as need for analgesia during 
menstruation. 
●​ Subjects will be asked to record their nausea and pain level using a numerical 
scale rating at the 6-8 hour mark after administration of misoprostol. After 24 
hours of administration, they will be asked their maximum pain score over the 
course of the first 24 hours. The subjects will have the option to either record 
their pain scores in a log or to text their pain scores directly to a designated 
phone number. Contact via text message will be encouraged as this will allow 
for live feedback and reduce recall bias 
●​ Subjects will be asked how satisfied they were with their overall experience 
(Very satisfied/Fairly satisfied/Neither satisfied nor dissatisfied/Fairly 
dissatisfied/Very dissatisfied). They will also be asked how likely they are to 
recommend this pain/antiemetic regimen method to a friend (Extremely 
likely/Likely/Neither likely nor unlikely/Unlikely/Extremely unlikely /Don’t 
know). 
●​ Data from the survey will be stored in the secure encrypted database of red 
cap when it is obtained  
 
6.7. Concomitant medication (if applicable): the medications for medical abortion 
itself, mifeprex and misoprostol  
6.8. Preparation/ Handling/ Product storage (and stability if applicable)/ 
Accountability: n/a 
6.9. Packaging and labeling (if applicable): n/a 
6.10. Follow-up and end-of study (if applicable)  
●​ Researchers will contact participants 3-5 days thereafter to collect and/or 
verify information on their pain and nausea scales and determine adherence 
to treatment regimen. They will also collect information on supplemental 
analgesia and anti-emetics that may have been used. 
●​ Patients will be asked to return for follow up visit to determine abortion status. 
Information on successful abortion will also be collected at the follow up visit. 
6.11. Study discontinuation (if applicable): if adverse events occur during the 
study 
6.12. Risks 
Risk of taking additional medication for management of pain and nausea if ibuprofen 
or ondansetron is taken prophylactically.  
Risk of taking ibuprofen as stated on box:  
Cardiovascular Thrombotic Events 
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Non-steroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of 
serious cardiovascular thrombotic events, including myocardial infarction and stroke, 
which can be fatal. This risk may occur early in treatment and may increase with 
duration of use. 
Ibuprofen Tablets is contraindicated in the setting of coronary artery bypass 
graft (CABG) surgery. 
Gastrointestinal Risk 
NSAIDS cause an increased risk of serious gastrointestinal adverse events including 
bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. 
These events can occur at any time during use and without warning symptoms. 
Elderly patients are at greater risk for serious gastrointestinal events. 
Risk of taking ondansetron as stated on box: 
Get emergency medical help if you have signs of an allergic reaction to 
ondansetron: rash, hives; fever, chills, difficult breathing; swelling of your face, lips, 
tongue, or throat. 
Common ondansetron side effects may include: diarrhea or constipation, headache, 
drowsiness, or tired feeling. 
Risk of breach of confidentiality  
6.12.1 Mitigation of risk (if applicable): will instruct subjects on the maximum dose 
of each medication so as not to exceed the daily maximum value 
6.13. Benefits 
6.13.1 Benefits for study participants: possible increased overall satisfaction with 
process of medical abortion. Less pain and nausea associated with treatment given 
medications are taken before experiencing pain or nausea 
6.13.2 Benefits for society: develop an ideal pain and anti-nausea management 
regimen for medical abortion which may benefit others in the future  
 
7 – Study Assessments and Procedures 
7.1. Safety Assessment 
A check in will be done with the subjects 3-5 days after treatment and a follow up 
appointment will be made 2 weeks after completion of treatment to ensure 
successful medical management and patient well-being. Should a patient require 
other interventions such as be admitted for acute blood loss anemia secondary to 
heavy bleeding during medical abortion or require surgical intervention due to failed 
medical management, this will be recorded in the subject record. The study does not 
increase their risks of having complications related to medical abortion itself. This 
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study is extremely safe, the only additional risk to the subject is taking an additional 
dose of ibuprofen or ondansetron for management of side effects related to medical 
abortion. 
7.2. Efficacy Assessment 
●​ Subjects will be asked to record their nausea and pain level using a numerical 
scale rating at the 6-8 hour mark after administration of misoprostol. After 24 
hours of administration, they will be asked their maximum pain score over the 
course of the first 24 hours. The subjects will have the option to either record 
their pain scores in a log or to text their pain scores directly to a designated 
phone number. Contact via text message will be encouraged as this will allow 
for live feedback and reduce recall bias 
●​ Researchers will contact participants 3-5 days thereafter to collect and/or 
verify information on their pain and nausea scales and determine adherence 
to treatment regimen. They will also collect information on supplemental 
analgesia and antiemetics that may have been used. 
●​ Subjects will be asked how satisfied they were with their overall experience 
(Very satisfied/Fairly satisfied/Neither satisfied nor dissatisfied/Fairly 
dissatisfied/Very dissatisfied). They will also be asked how likely they are to 
recommend this pain/antiemetic regimen method to a friend (Extremely 
likely/Likely/Neither likely nor unlikely/Unlikely/Extremely unlikely /Don’t 
know). 
●​ Ask the patient to return for follow up visit to determine abortion status. 
 
7.3. Other Assessment (if applicable): n/a 
7.4. Unanticipated Problems, Adverse Events and Serious Adverse Events 
7.4.1. Definitions: see above, the study does not increase the risks associated with 
medical abortions. The main adverse event to be alert for are patient’s with unknown 
allergies to ibuprofen or ondansetron.  
7.4.2. Grading/ Classification: n/a 
7.4.3. Expectedness: n/a 
7.4.4. Reporting: if there is an adverse event it will be reported to the IRB 
 
8 – Statistical Considerations 
8.1. Statistical Hypothesis 
Prophylactic use of ondansetron and ibuprofen will lead to statistically significant 
lower pain and nausea scores during medical abortion treatment and will increase 
patient satisfaction scores. 
8.2. Sample size consideration: Plan for 168 subjects in total. Power analysis: Two 
independent study groups, continuous, group 1 mean 7 (+/- 3), group 2 mean 5.5, 
alpha 0.05, power 0.9 
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8.3. Statistical Analysis Plan 
Intention to treat analysis will be performed. Analysis will be completed at the end of 
the study.  
 
9 - Trial Administration 
9.1. Ethical Considerations 
The study will be conducted according to the International Conference on 
Harmonization (ICH), Good Clinical Practice (GCP), the Declaration of Helsinki, 
Institutional Review Boards (IRB) and in accordance with the U.S. Code of Federal 
Regulations on Protection of Human Rights (21 CFR 50). 
9.2. Institutional Review Board (IRB) Review (list the IRB of record): This study 
will be submitted to the Hackensack Meridian Health IRB 
9.3. Protocol Adherence and Protocol Amendments: n/a 
9.4. Data and Safety oversight  
The Principal Investigator and the Co-Investigators will be responsible for the data 
and safety monitoring of this trial. This study is considered a minimal risk study which 
will have real-time monitoring by the PI and study team. 
The Principal Investigator and the Co-Investigators will review the data, including 
safety monitoring, at [study specific] meetings and on an on-going/as needed basis 
at teleconferences.  All Severe Adverse Events (SAEs) are required to be reported to 
the IRB.  
9.5. Data management (collection, storage etc.): data will be collected and stored 
in RedCap 
9.6. Privacy and Confidentiality 
Data will be kept in the encrypted RedCap system. Each subject will be given a code 
to maintain confidentially. Only the members of the research team will have access 
to the data.  
9.7. Informed consent: Informed consent will be obtained prior to enrollment into 
the study when the patient seeking medical abortion treatment during appointments 
with a family planning specialist. The patient will be given information about the 
study. Those who express interest will undergo a detailed informed consent process.  
The patient’s permission to use and share the information and data from this study 
will not expire. The patient may cancel this Authorization at any time by notifying the 
research team in writing. If the patient cancels this Authorization, the study doctor 
and staff will not use any new health information for research. However, researchers 
may continue to use the health information that was provided before the patient 
cancelled the authorization.​
​
Not signing the consent form or later canceling permission will not affect the subject’s 
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health care treatment outside the study, payment for health care from a health plan, 
or ability to get health plan benefits. However, if the subject does not give permission 
to use your health information, the subject may not take part in this study because 
their health information is needed in order to conduct the research.​
 
9.8. Data Quality Assurance (if applicable) 
All members of the research team will be trained to counsel the subjects on the study 
in a way that will make counseling standardized. Each subject will also be provided 
with instructions to go home with.  
9.9. Study Records (retention etc.) 
Records will be retained in accordance with regulatory, organizational and sponsor 
requirements, but for no less than two (2) years following the completion of the 
research.  Disposal of records will be done in such a manner that no identifying 
information can be linked to research data. 
9.10. Credentials, Training: n/a 
9.11. Financing and Insurance (if applicable): n/a 
9.12. Publication Plan and Data Sharing Plan: plan to publish data in 
peer-reviewed journal 
9.13. Conflict of Interest (if applicable): no conflict of interest 
 
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