Opioid Analgesia for MAB: A Randomized Controlled Trial
Phase: PHASE4
Conditions: MAB, Pain
Sponsor: Oregon Health and Science University

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
Page 1 of 17 
Revised: 6.11.2015 
 
 
 
 
 
 
 
 
Official Title:  
Opioid Analgesia for Medical Abortion: A Randomized Controlled Trial 
 
 
Principal Investigator: 
Alyssa Colwill, MD, MCR 
 
 
Professor, Department of Obstetrics and Gynecology 
Oregon Health & Science University  
 
 
 
 
 
NCT No: 
NCT03139240 
 
 
 
Protocol Version Date: 
December 20, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
Page 2 of 17 
Revised: 6.11.2015 
Protocol Template 
 
1. Protocol Title 
Opioid Analgesia for Medical Abortion: A Randomized Controlled Trial 
2. Objectives 
Objective 
Our primary objective will be to determine if a strong opioid, oxycodone, given at a dose 
recommended for severe pain in addition to ibuprofen decreases maximum pain scores 
compared to ibuprofen and placebo in women undergoing medical abortion. Results of 
this study will help future providers understand whether prescribing opioids are an 
important adjunct for pain control in women undergoing medical abortion. 
 
Hypothesis 
Women undergoing medical abortion up to 10 0/7 weeks who receive oxycodone and ibuprofen 
will report maximum pain scores at least 2 points lower on a numerical rating scale (NRS) 
compared to women receiving ibuprofen and placebo.  
 
Primary Outcome 
Maximum self-reported pain score on a NRS during the 24 hours after administration of 
misoprostol.  
 
Secondary Outcomes 
1. Maximal pain score stratified by gestational age (<7wks, 7-10 0/7wks). We have powered 
our study in order to have sufficient sample size for this outcome.  
2. Pain level at time of participant-reported expulsion using 11 point NRS (Do you think you 
have passed the pregnancy? (yes/no).  If yes: What was your worst pain at that time? 
3. Proportion of women reporting a maximum pain score >7 pain score  
a. Oxycodone versus placebo arm 
b. Stratified by gestational age groups (oxycodone versus placebo arm) 
4. Number of tablets of oxycodone and ibuprofen tablets used during the 24 hours after 
administration of misoprostol 
5. Use of rescue medication (yes/no) 
6. Number and chief complaints of subject initiated phone calls to the provider or clinic from 
time of mifepristone administration to scheduled follow-up appointment; for participants 
who do not show up to the follow-up visit, we will collect data on phone calls and 
complaints for 21 days following mifepristone administration. This information will be 
accessed through the Planned Parenthood of Columbia Willamette (PPCW) electronic 
medical record. 
7. Presence of Nausea/Vomiting within 24 hours 
8. Participant satisfaction with pain management (collected by text messaging survey: “Were 
you satisfied with the pain medications you received? (Yes/no)” 
9. Need for additional pain medications (marijuana, opioids they had access to): “Did you use 
any additional pain medications or substances other than what was given to you through 
the study? (Yes/no)”; If yes: “What did you use? Freetext response)” 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Revised: 6.11.2015 
10. Adequacy of blinding: “Do you believe you took oxycodone or a placebo? 
(oxycodone/placebo)” 
11. Adverse events  
 
3. Background 
Medical abortion is very common with over a quarter million performed in the United States in 
2011.1 Medical abortion, induced by the selective progesterone-receptor modulator, 
mifepristone, and prostaglandin analogue, misoprostol, has been widely researched to optimize 
dosing.2 However, abortion-related pain has not been systematically studied in clinical trials, 
limiting our ability to recommend appropriate analgesia.3 Medical abortion has been described 
as painful in 36-86% of patients.4-6 Up to one-third of women reported more pain than 
anticipated and found the magnitude of pain unacceptable.5,7 
 
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of analgesia regimens for 
abortion-related pain. NSAIDs inhibit the action of cyclooxygenase, an enzyme responsible for 
the formation of prostaglandins, which are known to cause cramping abdominal pain.8 NSAIDs 
do not interfere with the action of misoprostol to induce uterine contractions and pregnancy 
expulsion in women undergoing medical abortion.9 One randomized trial found that ibuprofen 
was more effective than acetaminophen for pain relief for medical abortion.10 Another study 
using prophylactic versus treatment ibuprofen failed to show a difference in pain control for 
medical abortion.11 However, NSAIDs do not provide sufficient pain relief for many women 
undergoing medical abortion with almost half still citing maximum pain scores between 8-10 on 
a 11-point numeric rating scale.11 
 
Opioid analgesia is often prescribed as an adjunct to NSAIDs to aid in pain control for medical 
abortion, with up to 79% of patients using at least one dose when prescribed.12 However, there 
is scant evidence to support using this treatment for reducing cramping experienced during 
medical abortion; only one randomized controlled trial exists, and it did not demonstrate an 
improvement in pain.13 No provider consensus exists regarding the provision of opioids for 
medication abortion. If an opioid is provided, there is also substantial variation to the dose, 
amount, and type given. Further research is necessary to evaluate opioid use during medical 
abortion since it is a medication that is not without side effects and cost.  
 
Immediate release oxycodone has a rapid onset with analgesia noted as early as 10 minutes, 
peaking at one hour, and lasting for 4 hours, and is prescribed for severe pain. In a randomized 
double blind control trial in patients with moderate to severe pain, oxycodone 5mg/ibuprofen 
400mg provided significantly greater analgesia compared to oxycodone 5mg/acetaminophen 
325mg and hydrocodone 7.5mg/acetaminophen 500mg.14,15 The one prior study using an opioid 
for medical abortion used the less potent analgesic of acetaminophen with codeine, potentially 
under-utilizing the analgesic properties of opioids for the severe pain experienced by women 
undergoing medical abortion. By using a more potent opioid for severe pain, we may be more 
likely to detect a benefit of using opioids and decrease overall pain experienced during medical 
abortion. 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Revised: 6.11.2015 
Planned Parenthood of Columbia Willamette (PPCW) Beaverton Health Center has not been 
routinely prescribing opioids for medical abortion. An internal review revealed no changes in 
overall patient satisfaction and no increase in provider phone calls. They performed 680 medical 
abortions in the past year.  
 
4. Study Design 
This is a randomized, double-blind, placebo-controlled trial of women undergoing medical abortion 
through 10 0/7 weeks to compare maximum pain scores in women receiving oral oxycodone 10mg 
and ibuprofen 800mg compared to ibuprofen 800mg and placebo beginning at the time of 
misoprostol administration.  
 
This study will be conducted at PPCW in Oregon. Potential participants will be approached by study 
staff after confirming the decision to proceed with medical abortion. Study procedures will be 
initiated following approval of the institutional review board (IRB) at Oregon Health and Science 
University (OHSU) as well as approval from Planned Parenthood Federation of America (PPFA). 
 
Following written informed consent, women will be stratified based on gestational age of <7 weeks 
or 7-10 weeks and then randomized to either oxycodone or placebo arm. Randomization will occur 
using a predetermined computer-generated blocked randomization and will be allocated using 
sequentially numbered, opaque, sealed envelopes prepared and pre-packaged by the OSHU 
research pharmacy. Study staff, investigators, and participants will be blinded to study arm 
allocation. Placebo and study drugs will be similar in appearance due to over-encapsulation of 
study drugs by the OHSU research pharmacy. Study drug allocation and study medications will be 
given out in a consecutive fashion stratified by gestational age. For example, study medications 
will be labelled as follows: subject #5, <7 weeks. Study staff will dispense the study medications to 
each subject at PPCW.  
 
Study staff will initiate a test text message while the subject is in the clinic to test her phone. Text 
messages through the TextIt platform will be utilized to send timed questions for data collection. 
The account will be linked to a dedicated study telephone and the number will be provided to study 
participants. 
 
Drug Dosing Guidelines for Pain 
Initial dosing:  
 Placebo Arm: Subjects will take ibuprofen 800mg just prior to misoprostol administration. 
They will take placebo at the start of painful uterine contractions.  
 Study drug (oxycodone) Arm: The oxycodone arm will take ibuprofen 800mg just prior to 
misoprostol administration. They will take oxycodone 10mg at the start of painful uterine 
contractions.  
 
Re-dosing: Subjects will be able to re-dose ibuprofen 800mg every 8 hours as needed.  
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Revised: 6.11.2015 
Rescue dosing: All subjects will be provided with a prescription for six tablets of oxycodone 5mg 
that they will be able to fill at their discretion. They will be able to take one tablet every 4 hours as 
needed.  
 
Maximum pain scores using 11-point NRS (0-10) will be assessed 6-8 hours and 24 hours after 
misoprostol administration. A reminder text message and phone call will be sent out if a subject 
has not responded to text messages.  
 
After the follow up visit or 21 days after mifepristone for subjects lost to follow up, review of the 
Planned Parenthood medical record charts will confirm completion of the medical abortion and 
review the number of unanticipated patient phone calls. If a participant is found to have an ongoing 
pregnancy, pain score data will not be collected beyond the 24 hours after the initial misoprostol 
administration. All unused study medication may be returned at the follow-up visit.  Subjects will 
not be required to return study medication, as study staff may not be present at their follow up 
visit.  However, if they choose to return study medication, this will be collected by Planned 
Parenthood or study staff.  
 
In case of emergency, questions, or the need to take the rescue medication, subjects will be 
provided with the dedicated study telephone number. 
 
 
Subjects will be compensated for their time and involvement in the study.  
 
The primary outcome will be the difference in maximum pain score reported within 24 hours after 
the administration of misoprostol. We anticipate a very small number of women needing 
additional doses of misoprostol to complete their abortion, and as such, we will not collect pain 
data beyond the first 24 hours if additional dosing or a surgical intervention is needed. If 
participants do not respond to text messaging or do not complete their scheduled follow up 
appointment, we will attempt to text twice and call once. For all subjects, study participation is 
complete at the follow-up visit or 14 days following mifepristone administration. We will be 
following the SPIRIT guidelines for study design and CONSORT guidelines for reporting our trial.16,17 
 
5. Study Population 
a. Number of Subjects 
Recruitment will occur at PPCW Beaverton Health Center in Oregon. 680 medical abortions were 
performed within the last calendar year at the Beaverton clinic which averages to 56 medical 
abortions per month. Two-thirds of these patients were <7 weeks and the remaining one-third was 
7-10 weeks gestational age.  
 
After written consent has been obtained and text messaging capabilities have been confirmed, 
participants will be stratified by gestational age group and then randomized in a 1:1 allocation to 
the oxycodone and placebo groups. Randomization will be assigned using two computer-
generated randomization lists (one for each stratum). Each block cell will include 43 subjects for a 
total of 172 subjects. The study medication or placebo capsules will be placed in identical packets, 
labelled only with the study identification number and instructions for use so as to maintain 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Revised: 6.11.2015 
blinding in accordance with the allocation scheme. Investigators will assign each participant a study 
identification number in sequential order as they enroll, and they will receive the study medication 
packet with that same identification number, stratified by gestational age groups.  
 
b. Inclusion and Exclusion Criteria 
Subjects will be approached about this study after the decision to proceed with medical abortion 
has occurred. Study staff will approach women at PPCW. Women will be informed that they can 
participate in the study by their own free will, that their care will not change whether they choose 
to participate or not, and that they can be removed from the study at any time without penalty.  
 
Subjects will receive detailed information regarding the study and an OSHU IRB approved consent 
form available in English will be reviewed and signed with interested participants. The patient’s 
medical chart will be reviewed and demographic and medical history will be collected to ensure 
eligibility. The study coordinator will send out a test text message to ensure the subject has text 
messaging capabilities. A recruitment log will track subjects who are excluded at any point 
throughout the study, or who decline entry. Their age, gestational age, and reason for exclusion or 
refusal will be documented. Patients will not have access to other opioid prescription medications 
outside of the study. 
 
Subjects in this RCT will be recruited from women who have consented for an elective medical 
termination of pregnancy up to 10 0/7 weeks gestation dated by ultrasound at PPCW. 
 
Inclusion criteria:  
 
-Aged 18 years or older 
 
-Seeking elective medical abortion 
 
-In good health and eligible for a medical abortion as defined by PPCW protocols 
-Pregnancy with intrauterine gestational sac up to 10 0/7 weeks, dated by ultrasound; or otherwise deemed 
eligible for a Medical Abortion by PPCW standards and guidelines protocol 
 
-Able and willing to receive SMS messages via phone 
 
-Ability to speak and read English  
 
-Able and willing to give informed consent and agree to the study terms 
 
-Have assistance at home; no motor vehicle use while taking study medications 
 
Exclusion criteria:  
 
-Lack of access to cell phone and texting capabilities 
 
-Early pregnancy failure 
-Contraindications to the study medications: Oxycodone, Ibuprofen 
 
-Contraindications to medical abortion with Mifepristone or Misoprostol   
 
-History of methadone or heroin use  
 
-Use of alcohol anytime from time of consent until completion of second text message questionnaire  
 
-Used marijuana >4 times per week in the last week 
 
 
-Any opioid in the past 30 days (ex: Vicodin, hydrocodone, hydromorphone, codeine, oxycodone, 
 
tramadol, fentanyl) 
           -Previously enrolled in this study 
 
Confidentiality of personal health information will be maintained according to HIPAA requirements for research. 
All subjects will receive a study number to which all subsequent data will refer. Personal identifiers will not be 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Revised: 6.11.2015 
on questionnaires, data, abstract sheets, or in the main database. All data will be kept in locked files or a 
password protected computer.  
 
The data collected for subjects who are unable to be randomized in this study will be kept until study 
completion and all data has been analyzed. All study charts will remain on-site at PPCW until participant has 
completed study or until completion of study. At that point, study charts will be brought to OHSU. Study charts 
will be kept in a locked cabinet in a locked office when not being used by study staff.  
 
c. Vulnerable Populations 
Pregnant women are the subjects of this study. Planned Parenthood requires women to be capable of 
giving voluntary informed consent in order to receive abortion services. Subjects will need to be able to 
provide voluntary informed consent to participate in this study. This study will not target decisionally-
impaired adults, non-English speaking patients or prisoners.  
 
d. Setting 
Recruitment, consenting, study procedures, and data analysis will occur by OHSU personnel at PPCW. 
Data analysis will also occur at OHSU. OHSU Research Pharmacy Services will prepare, compound, and 
distribute our medications. We are relying on the OHSU Institutional Review Board (IRB) to satisfy IRB 
review requirements. 
 
Recruitment will occur at PPCW Beaverton Health Center in Oregon. 680 medical abortions 
were performed within the last calendar year at the Beaverton clinic which averages to 56 
medical abortions per month. Upon OHSU IRB approval, PPFA will review study prior to study 
initiation.  
 
e. Recruitment Methods 
When patient’s check in for their medical abortion appointment at PPCW, they will receive 
handouts (“Study Fact Sheet” and “Flyer”) informing them that they may be approached about a 
medical abortion study being conducted at PPCW through OHSU. 
 
Study staff will approach patients at PPCW after they have confirmed their desire to have a 
medical abortion. Women will undergo the standard assessment and care for medical abortion 
at PPCW, which includes directly observed dosing of Mifepristone 200mg. Interested patients will 
undergo screening to determine eligibility. Screening will be conducted in the form of chart 
review by study staff.  Screening information will be kept in a de-identified screening log (# of 
people qualified or not qualified).  If eligible, interested participants will have time to review the 
consent and ask questions. The OHSU IRB approved consent will be signed by the participant and 
study staff.  
 
A questionnaire will be given by study staff to determine if the participant is eligible for the study. 
Subjects will receive detailed information regarding the study and an OSHU IRB approved consent 
available in English will be signed with interested participants. The patient’s medical chart will be 
reviewed and demographic and medical history will be collected. The study coordinator will send 
out a test text message to ensure the subject has text messaging capabilities. A recruitment log 
will track subjects who have signed consent and complete the study, as well as those who are 
excluded at any point throughout the study, or who decline entry. Their age, gestational age, and 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
Page 8 of 17 
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reason for exclusion or refusal will be documented. Patients will not have access to other opioid 
prescription medications outside of the study. 
 
Subjects will be contacted via phone using SMS text messaging. 
 
We will collect the following data at 6-8 hours post-misoprostol use: 
1. Did you take misoprostol? Text “Yes” or “No” 
2. What is your current pain? Please respond with a number0-10? 0 = no pain and = 10 worst possible pain 
3. What was your worst pain since taking misoprostol? (Reply 0-10) 
4. How long did your worst pain last in hours and minutes? (Reply hh:mm) 
5. Did you take the study medication for pain? Text YES or NO 
a. If yes, What time did you take the study medication? (Reply hh:mm) 
We will collect the following data at 24 hours post-misoprostol use: 
1. What is your current pain? Reply with a number 0-10? 0 = no pain and = 10 worst possible pain 
2. What was your worst pain over the past 18 hours? (Reply 0-10) 
3. How long did your worst pain last in number of hours and minutes? (Reply hh:mm) 
4. How many ibuprofen tablets did you use? (Reply 0-9) 
5. Did you require any oxycodone from the paper prescription for pain? (Reply YES or NO) 
a. If yes: How many tablets did you use? (Reply 0-6) 
6. Did you experience nausea or vomiting over the past 24 hours? (Reply YES or NO) 
7. Were you satisfied with the pain medications you received? (Reply YES or NO) 
8. Did you take the study medication for pain? (Reply YES or NO) 
a. If yes, Do you believe you took oxycodone or a placebo? (Reply OXYCODONE or PLACEBO) 
9. Did you use any additional pain medications or substances other that what was given to you through the 
study? (Reply YES or NO) 
a. If yes: What did you use? 
10. Did you use any non-medical therapies for pain, such as heat or massage? 
a. If yes: What did you use? 
11. Do you think you have passed the pregnancy? (Reply YES or NO) 
a. If yes: What was your worst pain at that time? (Reply 0-10) 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Subjects will be compensated up to $100 for their participation in the study. Subjects will be 
paid based on the number of study visits and text message responses they complete.  
Subjects will receive: 
 $10 dollars after agreeing to participate and after signing consent 
 $50 dollars for completing all text message surveys after taking Misoprostol ($25 per 
survey)  
 $40 for completion of follow-up appointment at PPCW 
 
Consent Process 
Study staff will approach patients at PPCW after they have confirmed their desire to have a medical 
abortion. Women will undergo the standard assessment and care for medical abortion at PPCW, which 
includes directly observed dosing of Mifepristone 200mg. Interested patients will undergo screening to 
determine eligibility in a private room at PPCW. If eligible, interested participants will have time to 
review the consent and ask questions. The OHSU IRB approved consent will be signed by the participant 
and study staff.  
 
Ongoing consent will be reviewed on a monthly basis. In order to meet our 12 month recruitment goal, 
thirteen subjects must be enrolled monthly. PPCW-Beaverton sees 56 subjects per month on average for 
medical abortion. The principal investigator will staff a medical abortion clinic in order to maximize 
recruitment potential and decrease burden on the PPCW clinic. 
 
6. Procedures Involved 
Subjects will be approached after the decision to proceed with medical abortion has occurred. Study staff will 
approach women at PPCW. Women will be informed that they can participate in the study by their own free will, 
that their care will not change whether they choose to participate or not, and that they can be removed from the 
study at any time.  
 
Subjects will receive detailed information regarding the study and an OSHU IRB approved consent available in 
English will be signed with interested participants. The patient’s medical chart will be reviewed and demographic 
and medical history will be collected. The study coordinator will send out a test text message to ensure the subject 
has text messaging capabilities. A recruitment log will track subjects who are excluded at any point throughout 
the study, or who decline entry. Their age, gestational age, and reason for exclusion or refusal will be documented. 
Patients will not have access to other opioid prescription medications outside of the study. 
 
After written consent has been obtained and text messaging capabilities have been confirmed, participants will 
be stratified by gestational age group and then randomized in a 1:1 allocation to the oxycodone and placebo 
groups. Randomization will be assigned using two computer-generated randomization lists (one for each stratum). 
Each block cell will include 43 subjects for a total of 172 subjects. The study medication or placebo capsules will 
be placed in identical packets, labelled only with the study identification number and instructions for use so as to 
maintain blinding in accordance with the allocation scheme. Investigators will assign each participant a study 
identification number in sequential order as they enroll, and they will receive the study medication packet with 
that same identification number, stratified by gestational age groups.  
 
At the time of randomization, subjects will be shown an 11-point Numeric Pain Rating Scale (NRS) handout (See 
Appendix A) and allow for any questions about responding to questions relating to reporting pain.20 Data will 
mainly be collected via SMS messaging using timed surveys at 6-8 and 24 hours. Final data will be completed via 
chart review after the scheduled follow-up visit or 21 days after mifepristone administration. 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
Page 10 of 17 
Revised: 6.11.2015 
If a participant does not respond to text messaging, we will attempt to contact the participant via text message 
twice, and call once. If a participant does not come to their follow up appointment, we will again attempt to 
contact by text message and phone call. If a participant receives care at another facility, we may request records 
from that facility for review. 
 
 
Subjects have the right to withdraw from the study at any time. Once a participant indicates their request for 
withdrawal, no further data will be collected. Participants will be provided with contact information and their 
reason for discontinuation will be recorded.   
 
No laboratory evaluations will be conducted for this research study. Women will receive a follow-up ultrasound 
as standard of care to evaluate completion of the medical abortion per Planned Parenthood guidelines.  
 
Data management will be managed by the PI. Baseline data will be collected at the initial visit by the study 
coordinator and PI. All data being collected after administration of misoprostol and study medications will be 
collected and stored on a secure server. Data regarding completion of medical abortion will be followed up via 
chart checking the electronic medical record of Planned Parenthood (NextGen). 
 
All subject data will be kept confidential and locked in an office and on a password-protected computer. Each 
subject will be assigned a unique study identification number. A file linking subjects with their study ID and name 
will be kept in a locked file in the PI’s office and stored separately from the data files. Only the study investigators 
will have access to this file. No subject names will be included in the study data during statistical analysis. The 
study coordinator and PI’s telephones will be encrypted by OHSU and password protected. 
 
Periodically, data will be pulled from the server and entered into REDCap and STATA. Random data entry checks 
will be performed to verify accuracy. 
 
Oxycodone HCl (Roxicodone) 5mg and 10mg tablets- Immediate-release oral formulation of oxycodone HCl 
indicated for the management of acute and chronic moderate to severe pain. Oxycodone is a semi-synthetic opioid 
with multiple actions qualitatively similar to those of morphine; the most prominent of these involves the central 
nervous system and organs composed of smooth muscle. Chemically, oxycodone hydrochloride is 4, 5α-epoxy-14-
hydroxy-3-methoxy-17methylmorphinan-6-one hydrochloride. It has the following structural formula: 
 
 
The 10mg dose is manufactured by:  
Zydus Pharma USA Inc 
73 NJ-31, Pennington, NJ 08534 
The 5mg dose is manufactured by: 
Epic Pharma LLC 
227-15 N Conduit Ave, Jamaica, NY 11413 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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Full prescribing information: 
http://labeling.pfizer.com/showlabeling.aspx?id=620 
 
Ibuprofen (Motrin) - Subjects will be taking 800mg tablets. Ibuprofen is a nonsteroidal anti-inflammatory drug. Its 
mode of action is not completely understood, but may be related to prostaglandin synthetase inhibition. 
Ibuprofen is (+) -2- (p – isobutylphenyl) propionic acid. Its chemical structure is: 
 
Manufacturer: 
Major Pharmaceuticals 
17177 North Laurel Park Suite 233 
Livonia, MI 48152 
Full prescribing information: 
http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/017463s105lbl.pdf 
 
7. Data and Specimens 
a. Handling of Data and Specimens 
 
Data management will be managed by study staff. Baseline data will be collected at the initial visit by 
the study staff. All data being collected after administration of misoprostol and study medications will 
be collected and stored on a secure server. Data regarding completion of medical abortion will be 
followed up via chart checking the electronic medical record of Planned Parenthood (NextGen). 
All subject data will be kept confidential and locked in an office and on a password-protected 
computer. Each subject will be assigned a unique study identification number. A file linking 
subjects with their study ID and name will be kept on a secure OHSU server and stored 
separately from the data files. Only the study staff will have access to this file. No subject names 
will be included in the study data during statistical analysis. The study staff’s telephones will be 
encrypted by OHSU and password protected. Periodically, data will be pulled from the server 
and entered into REDCap and STATA. Random data entry checks will be performed to verify 
accuracy. 
b. Sharing of Results with Subjects 
Data results will not be shared with subjects or their providers. 
 
c. Data and Specimen Banking 
The data collected in this study will be stored per FDA guidelines after completion of all data analysis 
and publication. Study data will not be used for further research. We are not collecting any specimens 
for this study. 
 
8. Data Analysis 
We will use descriptive statistics to characterize the sample and test for differences in baseline demographic 
and clinical characteristics between treatment groups using Student’s t-test, the Wilcoxon rank-sum test, 
Pearson’s chi-squared test, or Fisher’s exact test, as appropriate. 
 

 
OHSU IRB# 16845 
Protocol Version: 12.20.2017 
PI: Alyssa Colwill, MD MCR 
 
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For the primary and secondary outcomes, we will follow the intention-to-treat principle, including all 
participants who provide pain scores. Based on previous medical abortion pain studies11, we assume that 
maximum pain scores will not be normally distributed, so we will use a Wilcoxon rank-sum test to compare 
maximum NRS pain scores between the control and experimental groups. We will test for differences in 
NRS between the overall treatment groups and within gestational-age strata. For multivariable analysis of 
maximum pain scores, we will construct a proportional-odds cumulative logit model, a rank-based linear 
model, or a linear model on transformed data, depending on distribution of the data and model fit, with 
treatment group as the main predictor and adjusted for gestational age group and baseline demographic 
and clinical variables.  
 
To make use of the repeated pain measures, we will use a generalized estimating equation (GEE) 
to model pain scores during the first 24 hours.  
 
We will use logistic regression models to examine differences between groups in the following outcomes 
(all models will have treatment group as the main predictor and will be adjusted for gestational age group 
and baseline demographic and clinical characteristics):  
 
Proportion of women reporting a maximum pain score of 7 or higher. 
 
Use of rescue medication; this model will also adjust for the number of ibuprofen and oxycodone or 
placebo doses taken. 
 
Presence of nausea or vomiting 
 
Satisfaction with pain medication 
 
Need for additional (non-prescribed) pain medication 
 
To examine differences between groups in the amount of ibuprofen and oxycodone or placebo used during 
the 24 hours after administration of misoprostol, we will use Poisson, negative binomial, or zero-inflated 
Poisson or negative binomial regression models, depending on the distribution of the data. 
 
We will use descriptive statistics to characterize the number and chief complaints of patient-initiated phone 
calls to the provider or clinic. We will use Student’s t-test or a Wilcoxon rank-sum test to test for differences 
between groups in the number of calls placed. We will group chief complaints into broad categories and 
test for differences across treatment groups using a chi-squared test. Similarly, we will group non-
prescribed medications used for pain into broad categories and use descriptive statistics to characterize 
them.  
 
 
Finally, we will use descriptive statistics to summarize adverse events.  
 
Previous studies suggest that the 11-point numeric pain scale are as sensitive to changes in clinical pain as 
the visual analog scale.18 We will administer numeric pain scales via text message that will prompt 
participants to rate their pain on a scale of 0-10. Significant difference in pain intensity for the numeric 
pain scale is a change in >2.19 We will define a clinically significant change by a change in numeric pain of 
2.  
 
The sample size calculation was based on a simulation study using a Wilcoxon rank-sum test on data 
simulated from specified parameters (delta=2, sigma=2.6, alpha=0.05). It is difficult to simulate 
categorical data unless we assume a specific probability for each possible value of the NRS, which 
would be far too strong of a set of assumptions to make. For this reason, we treated the outcome 
as continuous and used a standard deviation as a measure of spread for the purpose of simulating 
data, and then used the more conservative rank-based test to calculate the sample. To calculate 

 
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sample size, we simulated pools of test and placebo ordinal NRS data whose means were 2 units 
apart and whose spreads were both 2.6 standard deviations. We selected these continuous and 
symmetric measures of center and spread in the absence of the availability of any other 
distributional assumptions of NRS data. The simulated pools of data were constrained to integer 
values ranging from 0 to 10. We repeatedly sampled from the simulated pools of data at sample 
sizes ranging from 10 to 100 per cell to calculate the probability of a significant (at alpha=0.05) 
Wilcoxon rank-sum test at each sample size. A sample size of 34 participants per group provided 
80% probability of detecting the 2-point difference in the simulated data. Initially, we anticipated a 
10% drop-out or study non-adherence and planned to enroll 38 participants per block cell (a total 
of 152 participants). After an interim analysis, 25% of participants are not using the study drug. 
While this is useful information for a secondary analysis, by increasing our sample size an additional 
15%, we can allow for 25% drop-out or study non-adherence in order to analyze our primary 
outcome. This would increase our overall enrollment goal to 172 (43 participants per group).  
 
9. Privacy, Confidentiality, and Data Security 
Data collection and storage: Standard institutional practices will be followed as described in the 
OHSU Information Security and Research Data Resource Guide 
(http://ozone.ohsu.edu/cc/sec/isg/res_sec.pdf) to maintain the confidentiality and security of 
data collected in this study. Study staff will be trained with regard to these procedures. Paper 
files will be stored in locked filing cabinets in restricted access offices at PPCW and OHSU. 
Electronic data will be stored in the secure web-based data collection system, REDCap, and 
TextIt which is housed on an OHSU secure server. Access to data is restricted to study personnel.  
Data coding: Upon enrollment, subjects will be assigned a code that will be used instead of their 
name, medical record number or other personally identifying information. Electronic files for 
data analysis will contain only the subject code. Codes will not contain any part of the 18 HIPAA 
identifiers (initials, DOB, MRN). The key associating the codes and the subjects’ personally 
identifying information will be restricted to the PI and study staff. The key will be kept secure on 
a restricted OHSU network drive a in a limited access folder.  
Final disposition of the data: The data collected in this study will be stored per FDA guidelines after 
completion of all data analysis and publication. Study data will not be used for further research. We are 
not collecting any specimens for this study. 
 
10. Provisions to Monitor the Data to Ensure the Safety of Subjects 
Please see Data Safety Monitoring Plan (DSMP).  
 
11. Risks and Benefits 
a. Risks to Subjects 
A foreseeable risk to participants participating in this research would be a breach of 
confidentiality. There are no anticipated inconveniences to study subjects related to 
participation in the research, as no additional procedures, tests or interventions will be 
performed apart from routine medical services provided to women seeking abortion care at 
Planned Parenthood. 
 
Another risk to taking part in this study is that the study drug or the dose a participant receive 
may not be effective in helping to treat their pain. This means subjects may spend time in the 
study and experience side effects taking a drug that may not provide subjects with any health-
related benefits. If a subject is not in the study, their treatment for pain during medical abortion 

 
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would be determined by PPCW which could include ibuprofen. By participating in the study, the 
only additional risk would be exposure to oxycodone if a subject is in the study drug group. 
 
If a participant is nursing an infant or planning to continue a pregnancy, then a participant is not 
eligible for the study. In the rare possibility that a medical abortion fails and a subject has an 
ongoing pregnancy and decides to keep the pregnancy, then the use of opioids and ibuprofen in 
the first trimester of pregnancy are category B. This means that the medication is generally safe 
to use during the first trimester of pregnancy, and the risks to the developing fetus are low. 
Extended use of oxycodone can result in neonatal withdrawal syndrome. Oxycodone crosses the 
placenta and is excreted in breast milk. Sedation or respiratory depression may occur in the 
infant. Ibuprofen is excreted into breast milk. Based on the available data, adverse events have 
not been reported in nursing infants and milk production is not affected. This study may involve 
risks to an embryo, fetus, or nursing infant that are currently unknown. 
 
b. Potential Benefits to Subjects 
Subjects may or may not personally benefit from being in this study. However, subjects will help 
us learn how to benefit patients in the future. 
 
12. Resources Available  
Subjects will have access via phone to a Family Planning trained Obstetrics and Gynecology 
specialist available during the length of the study for any questions or concerns. Subjects will be 
given the contact number for the Women’s Health Research Unit (WHRU) and the OHSU Paging 
Operator to ask to have on-call provider paged.  
 
13. Drugs  
The study drug (oxycodone) and ibuprofen used in this study have been approved by the Food 
and Drug Administration (FDA) for the treatment of pain. Study staff will follow the Research 
pharmacy policies and procedures. Study drugs will be prepared and handled by the pharmacy. 
Study staff will distribute the medications at PPCW. If not stored in the research pharmacy, 
medications will be maintained in a narcotic locker at the site. Subjects may return any unused 
medications at the end of study participation. 
 
 
14. Multi-Site Coordination (delete if not applicable) 
 
Planned Parenthood Federation of America (PPFA) will have the most current version of the protocol, 
consent and HIPAA authorization. PPFA will independently review the study. A research service 
agreement will be signed by OHSU and PPFA. All engaged participating sites will safeguard data as 
required by local information security policies. All local site investigators will conduct the study 
appropriately. All non-compliance with the study protocol will be reported in accordance with local 
policy. Communication of problems will be managed by the study PI. Interim results and study closure 
will be handled by the study PI. 
 
 
 
 
 
 

 
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References:  
(1) Jones, R. K., Jerman J. "Abortion incidence and service availability in the United States, 2011." 
Perspect Sex Reprod Health 2014;46(1):3-14. 
(2) Kulier R, GulmezogluAM, Hofmeyr GJ, et al. Medical methods for first trimester abortion. 
Cochrane Database Syst Rev 2004;(2). 
(3) Fiala, C., et al. "Pain during medical abortion, the impact of the regimen: a neglected issue? A 
review." Eur J Contracept Reprod Health Care 2014;19(6):404-419. 
(4) el-Refaey H, Templeton A. “Early abortion induction by a combination of mifepristone and oral 
misoprostol: a comparison between two dose regimens of misoprostol and their effect on blood 
pressure.” Br J Obstet Gynaecol 1994;Sep;101(9):792-6. 
(5) Raghavan S, Comendant R, Digol I, et al. “Two-pill regimens of misoprostol after mifepristone 
medical abortion through 63 days’ gestational age: A randomized controlled trial of sublingual 
and oral misoprostol.” Contraception 2009;79:84–90. 
(6) World Health Organisation Task Force on Post-ovulatory Methods of Fertility Regulation. 
“Comparison of two doses of mifepristone in combination with misoprostol for early medical 
abortion: A randomized trial.” BJOG 2000;107:524–30. 
(7) Winikoff B, Dzuba IG, Creinin MD, et al. “Two distinct oral routes of misoprostol in 
mifepristone medical abortion: A randomized controlled trial.” Obstet Gynecol 2008;112:1303–
10. 
(8) Marjoribanks, J., et al. "Nonsteroidal anti-inflammatory drugs for dysmenorrhoea." Cochrane 
Database Syst Rev 2015;(7):CD001751. 
(9) Creinin MD, Shulman T. Effect of nonsteroidal anti-inflammatory drugs on the action of 
misoprostol in a regimen for early abortion. Contraception 1997;56:165–8. 
(10) Livshits, A., et al. "Ibuprofen and paracetamol for pain relief during medical abortion: a double-
blind randomized controlled study." Fertil Steril 2009;91(5):1877-1880. 
(11) Raymond, E. G., et al. "Prophylactic compared with therapeutic ibuprofen analgesia in first-
trimester medical abortion: a randomized controlled trial." Obstet Gynecol 2013;122(3):558-564. 
(12) Westhoff C, Dasmahapatra, R, Schaff, E. “Analgesia during at-home use of misoprostol as part 
of a medical abortion regimen.” Contraception 2000;62:311–314. 

 
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(13) Wiebe E. “Pain control in medical abortion.” International Journal of Gynecology & Obstetrics 
2001;p74:275-280. 
(14) Lugo, R. A. and S. E. Kern. "The Pharmacokinetics of Oxycodone." Journal of Pain & Palliative 
Care Pharmacotherapy 2009;18(4):17-30. 
(15) Litkowski LJ, Christensen SE, Adamson DN, Van Dyke T, Han SH, Newman KB. Analgesic 
efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg compared with those of oxycodone 
5 mg/acetaminophen 325 mg and hydrocodone 7.5 mg/acetaminophen 500 mg in patients with 
moderate to severe postoperative pain: a randomized, double-blind, placebo-controlled, single-
dose, parallel-group study in a dental pain model. Clin Ther 2005;27(4):418–29. 
(16) Chan A., Tetzlaff J., Altman D., Laupacis A., Gøtzsche P., Krleža-Jerić K., Hróbjartsson A., 
Mann H., Dickersin K., Berlin J., Doré C., Parulekar W., Summerskill W., Groves T., Schulz K., 
Sox H., Rockhold F., Rennie D., Moher D.; SPIRIT 2013 Statement: Defining Standard Protocol 
Items for Clinical Trials. Ann Intern Med 2013;158:200-207. 
(17) Schulz KF, Altman DG, Moher D. CONSORT 2010 statement: updated guidelines for reporting 
parallel group randomised trials. BMJ 2010;340:c332. 
(18) Jensen M, Chen C, Brugger A. Interpretation of Visual Analog Scale Ratings and Change 
Scores: A Reanalysis of Two Clinical Trials of Postoperative Pain. The Journal of Pain 
2003;4(7):407-14. 
(19) Farrar J, Berlin J, Strom B. Clinically Important Changes in Acute Pain Outcome Measures: A 
Validation Study. J Pain Symptom Manage. 2003;25:406-11. 
(20) 0–10 Numeric Pain Rating Scale: From McCaffery M, Pasero C. Pain: Clinical Manual, St. 
Louis, 1999, P. 16. Copyrighted by Mosby, Inc. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Appendix A 
 
 
 
 
  0–10 Numeric Pain Rating Scale 
 
 
 
 
 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
Moderate 
Worst 
pain 
pain 
possible 
pain