Clinical trial NCT03136068
Conditions: Abortion
Sponsor: University of California, San Francisco
Start date: 2017-02-23; Completion date: 2018-05-31
Enrollment: 178 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a research study to measure the effect of digoxin injection on Dilation and Evacuation (D\&E) procedure duration. Digoxin is the most commonly used feticidal agent among family planning subspecialists, and is commonly used for a variety of reasons including provider preference, patient preference, and concerns over legal status of later D\&E procedures. There have been several studies on digoxin administration, adverse effects, and impact on the D\&E procedure, but doctors want to clarify how digoxin effects D\&E procedure time, if at all.

Detailed description:

Arms: arm 1: Subjects assigned to the intervention arm will receive a 1 mg intrafetal digoxin injection under ultrasound guidance arm 2: Subjects assigned to the control arm will receive an ultrasound-guided intrafetal saline injection of the equivalent volume
Interventions: intervention 1: Digoxin intervention 2: Placebo
Intervention descriptions: intervention 1: Trans-abdominal injection intervention 2: Trans-abdominal injection

Protocol documents:
Prot_SAP_000.pdf: 
Standard Operating Procedure - Intrafetal digoxin as an adjuvant for dilation and evacuation at 20 to 24 
weeks’ gestation: a placebo-controlled, double-blinded randomized controlled trial. 
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INTRAFETAL DIGOXIN AS AN ADJUVANT FOR DILATION AND EVACUATION 
AT 20 TO 24 WEEKS’ GESTATION: A PLACEBO-CONTROLLED, DOUBLE-
BLINDED RANDOMIZED CONTROLLED TRIAL 
 
 
SITE: University of California, San Francisco 
 
Women’s Options Center, San Francisco General Hospital, 
 
San Francisco, CA 
Site Investigators: Jennifer Kerns MD, MPH 
Site Study Coordinator:  Chiara Corbetta-Rastelli 
 
SITE: Lovejoy Surgicenter 
 
Portland, OR 
Site Investigators: Paula Bednarek, MD, MPH 
Site Study Coordinator:  Shannon Williams and Emily Padua 
 
SITE: FPA Women’s Health 
 
Long Beach, CA 
Site Investigators: Rachel Steward, MD 
Site Study Coordinator: Nicholas Brass 
 
SITE: FPA Women’s Health 
 
Los Angeles, CA 
Site Investigators: Rachel Steward, MD 
Site Study Coordinator: Nicholas Brass 
 
Standard Operating Procedures (SOPs) 


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TABLE OF CONTENTS 
Section                                                                                                             Page 
 
I. 
Introduction 
 
II. 
Study Materials 
A. Study Binder 
B. Forms 
C. Study medication 
D. Clinical supplies 
 
III. 
Flow Diagram of study procedures 
 
IV. 
Assessing study eligibility and participant enrollment 
A. Beginning the screening process 
B. Assessing inclusion criteria 
C. Assessing interest in study participation 
D. Administering informed consent 
E. Assessing exclusion criteria 
 
V. 
Data Collection 
A. Form 1: Eligibility Screening and Baseline Data, Day 1 
B. Form 2: Dilator and Injection Data, Day 1 
C. Form 3: Arrival Data, Day 2 
D. Form 4: Intra-operative Data, Day 2 
E. Form 5: Post-operative Data, Day 2 
 
VI. 
Study Logs 
A. Enrollment and Recruitment Log 
B. Protocol deviations log 
C. Payment Log 
D. Adverse events log 
E. Drug Management Log 
F. Participant Log 
G. Monitoring Log 
 
VII. 
Information exchange with the coordinating center 
A. Sending data collection forms 
B. Queries 
C. Sending logs to the coordinating center 
D. Protocol updates 
E. Delegation of Authority log  
 
VIII. 
Severe Adverse Events 
 
IX. 
Detailed Data Analysis plan 


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I. INTRODUCTION 
 
These Standard Operating Procedures (SOPs) provide instruction for study staff 
conducting the research study “Intrafetal digoxin as an adjuvant for dilation and 
evacuation at 20 to 24 weeks’ gestation: a placebo-controlled, double-blinded 
randomized controlled trial.” This study will investigate if the intrafetal injection of 
1mg of Digoxin 16-24 hrs preoperatively decreases operative time for women 
undergoing dilation and evacuation (D&E) at 20-4 0/7 wks gestation compared to 
women who receiving a placebo injection. This study will take place at 4 sites. 
The sites and their Site Codes are listed below: 
 
Site Code 
Site 
SF 
Women’s Options Center, San Francisco General Hospital, San Francisco, CA 
LJ 
Lovejoy Surgicenter, Portland, OR 
LA 
Family Planning Associates Women’s Health, Los Angeles, CA 
LB 
Family Planning Associates Women’s Health, Long Beach, CA 
 
These SOPs contain detailed instructions for implementing the study protocol for 
each study participant, including instruction for each item on the study data 
collection forms and logs. This research study must be carried out exactly as 
described in the protocol and all study staff must follow the same procedures for 
data collection and completion of forms and logs. Study staff must read and 
understand the research protocol, study forms, and these SOPs before study 
enrollment begins. 
 
These SOPs should be used as a reference over the course of this study to 
ensure that all study procedures are being conducted correctly. Questions about 
study conduct that are not answered in these SOPs should be directed to the 
site’s Principal Investigator or to the site manager at the coordinating center 
 
Project and site manager:  
Chiara Corbetta-Rastelli 
Chiara.Corbetta-Rastelli@ucsf.edu 
Cell: (314) 387-3575 
 
The procedures set out in the study protocol are designed to ensure that study 
staff abide by good clinical practice (GCP) guidelines. GCP is an international 
quality standard defined by the International Conference on Harmonisation (ICH), 
which defines standards for clinical trials involving human subjects. At a 
minimum, each study staff member must have completed a human subjects 
protection course that has been approved by the study coordinating center. 


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Study staff must also have attended a study training conducted by the 
coordinating center or received individual training in study procedures from an 
approved study staff member qualified to do so. Names of additions to study staff 
must be submitted to the coordinating center and approved by the overall 
Principal Investigator and applicable IRB before the new study staff may perform 
study procedures.  
 


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II. STUDY MATERIALS 
 
The coordinating center will provide each site with the study materials listed 
below. If any supplies are beginning to run low, site staff are responsible for 
contacting the site manager to request replenishments. Please request 
replenishments with enough advance notice (about 2 weeks) so that enrollment 
will not be interrupted. 
 
All study materials must be kept in a secure location accessible only to study 
staff. All study medications must be kept separate from the clinic’s regular 
supply.  
 
A. Study Binder 
The Study Binder will include the following materials: 
• FDA Study Protocol 
• Data Collection Forms 
• Standard Operating Procedures (SOPs) 
• IRB-approved, stamped consent form 
• HIPAA consent form 
• Subject Bill of Rights 
• Study staff log 
• Protocol deviations log 
• Payment log 
• Adverse events log 
• Protocol Updates 
• Monitoring log  
• IRB materials, including initial approval documentation, amendments, 
continuing reviews, corresponding approvals and correspondence 
 
B. Forms: 
Sites will be supplied with copies of each of the following forms: 
• Form 1: Eligibility Screening and Baseline Data, Day 1 
• Form 2: Dilator and Injection Data, Day 1 
• Form 3: Arrival Data, Day 2 
• Form 4: Intra-operative Data, Day 2 
• Form 5: Post-operative Data, Day 2 
 
C. Study medication 
 
D. Other site materials: 
• Stopwatch 
• Spinal Needles 


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• Cash Box 
• Color Folders: 
o For sites recruiting multiple gestational age groups (SF and LJ) 
multi-color folders will be provided to help differentiate the colored 
folders: 
 RED folders: Gestational Age Group 1 
• [BPD is measuring 4.61-5.24cm check “Group 1”] 
• For participants who are in Group 1, materials should 
be placed in a Red folder in order to avoid confusion 
as to which group they are. For Lovejoy Surgicenter, 
randomization envelopes will also be marked with 
Red ink to correspond. 
 BLUE folders: Gestational Age Group 2 
• [BPD is measuring 5.25-5.88cm check “Group 2”] 
• For participants who are in Group 2, materials should 
be placed in a Blue folder in order to avoid confusion 
as to which group they are. For Lovejoy Surgicenter, 
randomization envelopes will also be marked with 
Blue ink to correspond. 


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• III. FLOW DIAGRAM OF STUDY PROCEDURES 
 
 
 
 
 
 
 
 
 
 
 
 
 
Ultrasound 
Counseling 
Consent for Abortion 
ASSESS ELIGIBILITY  
Provide patients of correct age and gestational 
age study description via Recruitment Script 
If interested, complete items 3-17 on Form 1 to 
assess eligibility 
If eligible and wants to participate: 
INFORMED CONSENT 
Complete FORM 1: Eligibility & Baseline Info 
(Survey1) 
Interview patient regarding: 
 
Race/ethnicity 
 
Depression, anxiety 
 
Health during current pregnancy 
 
Current pain 
Check patient chart regarding: 
Reason for abortion 
Medication history 
If declined to participate, record 
reasons for declining on Form 1 Item 
2 and in the Recruitment Log 
If ineligible based on exclusion 
criteria record why in Recruitment 
Log 
Dilators placed  
RANDOMIZATION 
Pharmacist or staff member with no other study 
duties will draw up injection based on 
randomization number 
INJECTION 
FORM 2: Dilator & Injection Data (Survey2) 
Clinician questionnaire 
Patient injection tolerability and pain 
DAY 1 PAYMENT 
Record: (record on Form 2) 
- 
# and type of dilators used 
- 
Time of dilator placement 
- 
Additional meds given 
- 
Adjunctive mifepristone given 
- 
Patient’s pain after dilation 
Day 1 
FORM 3: Arrival Data Day2 (Survey3) 
Patient’s temperature  
Adverse events overnight 
Pain or nausea medications used overnight 
Pain on arrival 
Day 2 
Cont’d 
on next 
page 
Physician H&P 
Have clinician confirm eligibility criteria and sign 
Form 1 
Injection can occur before or after dilator placement 
LJ: injection first; FPAWH; dilators first, SF; either 


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Flow Diagram Continued 
 
PROCEDURE 
FORM 4: Intra-Operative Data 
RN assess cardiac activity (provider blinded) 
Record what anesthesia used 
Record if mechanical dilation 
Record time speculum inserted 
Start stopwatch/timer when speculum inserted 
Record time to first instrument insertion into uterus 
Record time to procedure done (per MD) 
Record time to speculum removal 
Note any complications or IUD used 
Immediately post-procedure 
FORM 4: Intra-Operative Data (cont’d) 
Record provider feedback & provider assessment of 
drug used 
Day 2 
 
Post-Procedure, in clinic recovery room 
FORM 5: Post-procedure Data 
Post-procedure pain 
Post-procedure adverse events 
Participant satisfaction 
Time participant discharged 
Recovery room data 
After participant leaves 
record recovery room data 
(Record on Form 5) 
DAY 2 PAYMENT 


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IV. ASSESSING STUDY ELIGIBILITY AND PARTICIPANT ENROLLMENT 
 
A. Beginning the Screening Process 
 
For the purposes of this study, a screened patient will be defined as one who 
was identified based on gestational age and procedure type (D&E), as being 
potentially eligible for the study and who was approached about study 
participation.  
 
B. Assessing interest in study participation 
 
Once staff have identified a patient who might be eligible, based on patient age, 
gestational age and procedure type, for study participation, study staff should 
approach the patient to gauge interest in participating in the study. Research staff 
should assess the patient’s interest in study participation by describing the study 
using the following study description. This study description is also printed on the 
Recruitment Script Form. Please adapt as needed. 
 
Digoxin RCT Recruitment Script 
 
Digoxin RCT Recruitment Script 
 
Hi my name is ___________ and I am a researcher. I am working on a study 
that you are eligible for, is it okay if I tell you a little bit about it? It is totally 
optional, so after you hear about it, it will be up to you to decide if you’re 
interested in being in the study.  
The study is on a medication called digoxin. Digoxin is FDA approved to 
treat heart conditions, but it is often used before abortions to stop the fetal 
heart from beating. In some clinics, all women who are having an abortion 
after 20 weeks of gestation receive digoxin, and in some clinics they don’t 
use this medication at all. Some doctors think that using digoxin helps to 
make the abortion procedure faster and easier, but we don’t know this for 
sure. That is why we’re studying digoxin; we want to know if using digoxin 
makes the abortion faster, easier and safer.  
If you decide to be in the study it will involve some things today and some 
tomorrow. I will ask you some questions to make sure it’s ok for you to be 
in the study, and then I would ask you a few questions about how you’re 
feeling today. Today you will be having dilators placed, and if you are in the 
study, you will also receive an injection in your abdomen. The injection will 
either be digoxin, which is the medication that we’re studying, or a placebo, 
which is salt water and doesn’t do anything. The study drug will be injected 
into the fetus. After the injection, you would answer a few more questions. 
Then tomorrow we will give you a quick survey before your procedure, 


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collect some information during your procedure, and give you another 
quick survey while you’re in the recovery room after your procedure.  
You will be paid $100 in total over the two days as a thank you for your 
time.  
If you choose not to participate in the study your care will not be affected in 
any way. You will/will not receive a digoxin injection today. (RA will tell 
them whether they will or will not receive digoxin depending on where they 
are having their abortion. SFGH: WILL NOT, FPAWH: WILL, Lovejoy: MAY 
OR MAY NOT depending on provider).  
 
For patients who are interested in participating, they should proceed to eligibility 
screening (Form 1) and consenting. 
  
For patients who were approached based on being recommended by clinic staff 
but declined to participate after hearing the Recruitment Script, their reason for 
declining should be recorded on Form 1 (Item 2) and logged in the Recruitment 
Log under the tab “Declined”. 
 
C. Assessing Inclusion Criteria 
 
Once staff have identified a patient who might be eligible and is interested in 
study participation, study staff should use Items 3-17 of Form 1 as a guide to 
assess inclusion and exclusion criteria. 
Inclusion criteria: (Items 3-7) 
- 
Female 
- 
18 years and older 
- 
English-speaking 
- 
Currently pregnant with singleton pregnancy 
- 
Seeking pregnancy termination between 20 0/7 weeks and 24 0/7 weeks 
gestation 
o Assessed via Biparietal Diameter on Day 1 between 4.61 and 5.88 
mm by transabdominal ultrasound measurement.  
- 
Medically eligible for outpatient Dilation & Evacuation procedure at clinical 
site 
- 
Requiring only one day of dilators prior to D&E 
- 
Able to give informed consent 
If a patient meets all inclusion criteria on Form 1 then study staff should proceed 
with assessing exclusion criteria. 
 
D. Assessing Exclusion criteria 
 
Following inclusion criteria assessment, patients who are still eligible should be 
screened for exclusion criteria. These are assessed using Items 8-17 of Form 1 


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Exclusion Criteria: (Items 8-17 Form 1) 
- 
Reason for abortion is fetal demise 
- 
Participant has contraindications to digoxin including but not limited to: 
o Known allergy to digoxin 
o Current cardiomyopathy or impaired systolic or diastolic function 
o History of heart attack 
o Current pericarditis 
o Any cardiac rhythm abnormalities 
o Current heart disease of any other type 
o Current uncontrolled thyroid disease (hypothyroidism or 
hyperthyroidism uncontrolled by medication) 
o Acute or chronic renal failure 
o Autoimmune renal disease 
- 
Participant requires more than one day of cervical preparation 
- 
Participant diagnosed with placenta accreta, increta or percreta 
- 
Participant diagnosed with preterm premature rupture of membranes 
(PPROM) 
- 
Participant diagnosed with anhydramnios 
- 
Participant has active bleeding or is hemodynamically unstable 
- 
Participant has signs of chorioamnionitis or any clinical infection (fever 
>100.4°F) 
 
Eligibility must be confirmed by a clinician or physician and must be documented 
using Form 1: Eligibility Screening and Baseline Data, Day 1. Detailed 
instructions for completing Form 1 can be found in the section V. A. of these 
SOPs.  
 
Women must meet ALL eligibility (both inclusion and exclusion) criteria to be 
considered eligible for this study. If a woman does not meet eligibility criteria she 
cannot participate in this study.  
 
If a woman does meet ALL eligibility criteria (both inclusion and exclusion) and 
wishes to participate in the study, she is ready to be consented. However, inform 
the patient that her eligibility is only confirmed when she sees the clinician, so 
there is the possibility of her being consented and later found ineligible for the 
study based on the clinician’s recommendations. 
 
E. Administering study informed consent 
 
The study Informed Consent Form (ICF) and HIPAA Consent Form (HCF) must 
be completed for all study participants. These forms must be signed and dated 
by the participant and an IRB approved study staff before any study procedures 
may take place. 


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If a woman may be eligible for study participation and would like to participate in 
the study, she should be given an ICF and HCF to read and they should be 
explained to her. IF the woman cannot read the forms, then the forms should be 
read and explained to her. Study staff should ensure that the woman 
understands the requirements of the study protocol, the risks and benefits of the 
study participation, potential side effects and complications and the voluntary 
nature of the study participation. The woman should be given the opportunity to 
ask questions and to have them answered by the appropriate study staff. 
 
If a woman agrees to participate in the study, she should sign and date the ICF 
and HCF. IRB-approved staff should also sign and date the ICF and HCF. Study 
staff should review the ICF and HCF to ensure that the patient has signed, the 
study staff has signed, and that both have written the correct date. If either the 
participant or study staff makes an error, she should cross out her mistake and 
clearly write the correction nearby. She should initial and date (MM/DD/YY) her 
correction. 
 
The signed copies of the ICF and HCF should be kept by the study site. The 
patient should be offered copies of the ICF and HCF for her records. Furthermore 
ALL study participants should be given a copy of the Participant Bill of Rights. 
 
Once the patient has signed the ICF and HCF, she is considered enrolled in the 
study. All enrolled participants should be asked to complete a records release 
form in the event that study staff need to request medical records from other 
institutions during the study period. After completion of the records release form, 
study staff should proceed with completing Form 1: Eligibility and Baseline 
Info, Day 1.  
 


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V. DATA COLLECTION 
 
For this study, there are [5] data collection forms and an informed consent form. 
The [number] data collection forms are as follows: 
• Form 1: Eligibility Screening Baseline Data, Day 1 
• Form 2: Dilator and Injection Data, Day 1 
• Form 3: Arrival Data, Day 2 
• Form 4: Intra-operative Data, Day 2 
• Form 5: Post-operative Data, Day 2 
 
The first form to be completed after signing the ICF is Form 1: Eligibility 
Screening and Baseline Data, Day 1. 
 
General Instructions for Data Collection Forms 
 
1. All data collection forms should be completed thoroughly and carefully by an 
IRB-approved study staff using black ink. All five of the data collection forms 
should be completed for all study participants. 
  
2. To make changes to a response on a data collection form, cross out the 
error using a single line, make the correction, and initial and date the 
change (MM/DD/YY) 
 
3. All questions directed to patients should be read to the patient as printed on 
the data collection forms. Similarly, response choices for patient questions 
should be read as printed. 
 
4. All questions assessing clinical information should be reviewed and 
confirmed by a clinician or physician.  
 
5. All questions directed to a clinician or physician may be answered directly 
on the study for by the clinician/physician. Alternatively, study staff may read 
the question to the clinician/physician and record his or her response. 
 
6. All forms should have the participant’s enrollment ID, the date, and the 
signature of staff member filling out the form completed.  
 


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A. Form 1: Eligibility Screening and Baseline Data, Day 1  
 
Form 1 Overview 
 
Form 1 is used to document study eligibility for patients who have signed the ICF. 
Thus included in the form is all the exclusion criteria for the study. It also records 
additional baseline clinical data and asks demographic questions of the 
participant.  
 
Form 1 Detailed Instructions 
 
1. Record the date that patient is screened for eligibility in the clinic. Dates 
should be recorded as month/date/year (MM/DD/YYYY) 
 
2. If the woman wants to participate in the study, check “Yes” and proceed 
with consenting the participant. Once she is consented, complete the rest 
of Form 1. If she does not want to participate, check “No” and stop all 
study procedures. 
 
a. If she does not want to participate, ask the woman her reason(s) for 
not wanting to participate and document her response on the line 
provided and in the Recruitment Log. If she does not wish to say, 
document “Declined to say” in the Recruitment Log. 
 
Items 3-17, the Eligibility Checklist, document the patient’s eligibility for study 
participation. Eligibility must be confirmed by a clinician or physician, typically at 
the time of the clinicians history taking with the patient. Complete items 3-17 
even if the patient is found to be ineligible based on her responses prior to 
finishing question 17. 
3. Check “Yes” if the patient is Age 18 or older. Check “No” if the patient is 
under age 18. 
 
4. Check “Yes” if the patient is seeking pregnancy termination and is 
between 20w0d and 24w0d with a Biparietal diameter (BPD) of 4.61 to 
5.88cm, inclusive, as assessed by ultrasound on enrollment day. Check 
“No” if the patient does not fit this criteria. 
 
a. Patients with cranial defects must be between 20w0d and 24w0d 
by best estimate of gestational age AND BPD must also be within 
range above. If cranial defects preclude BPD measurement, use 
the best composite sonographic dating criteria available to ensure 
the patient is between 20w0d and 24w0d. 


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b. For eligibility screening, record the gestation age that the patient or 
clinic staff provide. Once the patient has been consented, confirm 
the exact gestation age via BPD with the clinician. 
 
5. Check “Yes” if the patient can speak English. Check “No” if the patient is 
not able to speak English.  
 
6. Check “Yes” if the patient is carrying a singleton pregnancy (one fetus). 
Check “No” if the patient is carrying a multiple gestation pregnancy 
 
7.  Check “Yes” if the patient only required one day of dilator placement (aka 
dilators placed on the day prior to procedure). Check “No” if patient 
required dilator placement for longer than one day. 
 
8. Indicate if the patient is incarcerated by checking “Yes” or “No” 
 
9. Indicate if the patient is having active bleeding or if she is 
hemodynamically unstable at the time of eligibility assessment by 
checking “Yes” or “No”. 
 
10. Indicate if the patient has any signs of chorioamnionitis or a clinical 
infection, including if they have a fever >100.4°F, at the time of eligibility 
assessment by checking “Yes” or “No”.  
 
11. Indicate if the patient has a known allergy to digoxin by checking “Yes” or 
“No”. 
 
12. Indicate if the patient has any contraindications to digoxin in their medical 
history by checking “Yes” or “No”.  
 
a. Inquire specifically about: current cardiomyopathy or impaired 
systolic or diastolic function, history of heart attack, current 
pericarditis, any cardiac rhythm abnormalities, current heart 
disease of any other type, current uncontrolled thyroid disease 
(hypothyroidism or hyperthyroidism uncontrolled by medication), 
acute or chronic renal failure, autoimmune renal diseases. 
b. If the patient is unsure about her medical history with regards to 
any of the above listed criteria, record her response and confirm 
her medical history with the clinician after his or her assessment of 
the patient. 
 
13.  Indicate if the patient is presenting for her abortion procedure due to a 
known fetal demise (IUFD) by checking “Yes” or “No”. 


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14.  Indicate if the patient has previously participated in this study by checking 
“Yes” or “No”. 
 
15. Indicate if the patient has known preterm premature rupture of membranes 
(PPROM), defined as a rupture in the amniotic sac prior to labor at <37 
wks gestation, by checking “Yes” or “No”. 
 
16. Indicate if the patient has been diagnosed with anhydramnios during this 
pregnancy by checking “Yes” or “No”. 
 
17. Indicate if the patient has been diagnosed with placenta accreta (including 
increta and percreta) during this pregnancy by checking “Yes” or “No”. 
 
18.  Based on the answers to questions 3-17, ensure that the woman is 
eligible for the study. All checkmarks must be in the UNSHADED boxes 
for the patient to be considered eligible for study participation. If any 
checkmarks fall in the shaded area, then the patient is not eligible for 
study participation. If she is eligible for study participation, check “Yes” 
and proceed with consenting the patient. If she is not eligible for study 
participation, check “No” and stop all study procedures.  
 
a. If the participant is not eligible, inform them of their ineligibility and 
reiterate that their planned abortion procedure will continue without 
study participation.  
 
b. Document in the Screening Log the reason(s) for the participant’s 
ineligibility. 
 
c. If the participant is found eligible, remind the patient that her 
eligibility must be confirmed by the clinician for her to receive the 
injection. However, if she were to be found ineligible by the clinician 
she would still be compensated for her time. 
 
19. If the study ICF and HCF have been signed by both the woman and an 
IRB-approved study staff member who was responsible for conducting the 
study consent process, check “Yes” and proceed with Form 1. If not, 
check “No”, and stop all study procedures until the ICF and HCF are 
signed. A patient may only participate in the study if she has signed the 
ICF and HCF.  
 
20. All study participants should be offered a copy of the ICF and HCF for 
their records. They should also receive a copy of the Participant Bill of 


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Rights. Note whether copies were offered to the patient by checking “Yes” 
or “No”.  
 
As noted above, a clinician or physician must assess and confirm study eligibility. 
The clinician or physician who was responsible for assessing study eligibility 
must print and sign his/her name on the designated lines below Question 20. 
This may be completed after the rest of Form 1 is completed as the clinician may 
not be able to assess the patient until immediately before the dilator placement. 
However, Form 1 should be completed and signed prior to any dilator placement 
or study medication injection begins. 
 
If the answers to Q18-20 are all “Yes” then the participant should be given a 
study Enrollment ID. This Enrollment ID should be recorded in the header of all 
study forms. This Enrollment ID should also be recorded when completing the 
patient’s entry in the electronic Enrollment Log. Detailed instructions for 
completion of the Enrollment Log can be found in Section VI. A.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Study Enrollment ID assignment 
 
The Enrollment ID of each participant includes both the standard code for her 
study site and an individual numerical code specific to each participant. Once a 
participant is randomized to either the digoxin or placebo group she will also 
have a separate Randomization ID, discussed further in Section V.B. Site ID’s 
are fixed per site as follows: 
• Women’s Options Center: SF 
• Lovejoy Surgicenter: LJ 
• FPAWH Los Angeles: LA 
• FPAWH Long Beach: LB 
Thus the first participant at Women’s Options Center would have the Enrollment 
ID SF001 and each subsequent participant would have the next Enrollment ID in 
numerical order. 
 
Women’s Options Center, 
San Francisco CA 
Lovejoy Surgicenter, 
Portland OR 
FPAWH, Los 
Angeles CA 
FPAWH, Long 
Beach CA 
SF001 
LJ001 
LA001 
LB001 
SF002 
LJ002 
LA002 
LB002 
SF003 
LJ003 
LA003 
LB003 
SF004 
LJ004 
LA004 
LB004 
 
Once the patient has been assessed for eligibility, consented and assigned an 
enrollment number, complete Form 1 by asking the patient items 21-27. 
 
21. Ask the patient how she would describe her race or ethnicity. Record her 
response by ticking the appropriate box. If the patient reports a race or 
ethnicity that is not on this list of response choices, tick the box for “Other” 
and write in her reported race/ethnicity on the line. If the patient declines 
to answer the question, tick “Decline to answer”.  
 
22. Read the prompt prior to asking the questions under item 22. For each 
question under item 22, read the question as: 
 
a. Question a: “Over the last 2 weeks how often have you had little 
interest or pleasure in doing things” and read the 4 choices to the 
patient “ Not at all,” “Several days,” “More than half the days,” and 
“Nearly everyday”. Tick the appropriate response.  
 


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b. Question b: “Over the last 2 weeks how often have you been 
feeling down, depressed or hopeless” and read the 4 choices to the 
patient “ Not at all,” “Several days,” “More than half the days,” and 
“Nearly everyday”. Tick the appropriate response.  
 
c. Question c: “Over the last 2 weeks how often have you had trouble 
falling or stay asleep, or sleeping too much” and read the 4 choices 
to the patient “ Not at all,” “Several days,” “More than half the days,” 
and “Nearly everyday”. Tick the appropriate response. 
 
d. Question d: “Over the last 2 weeks how often have you been felt 
tired or had little energy” and read the 4 choices to the patient “ Not 
at all,” “Several days,” “More than half the days,” and “Nearly 
everyday”. Tick the appropriate response. 
 
e. Question e: “Over the last 2 weeks how often have you had a pore 
appetite or been overeating” and read the 4 choices to the patient “ 
Not at all,” “Several days,” “More than half the days,” and “Nearly 
everyday”. Tick the appropriate response. 
 
f. Question f: “Over the last 2 weeks how often have you been feeling 
bad about yourself, or that you are a failure or hae let yourself or 
your family down” and read the 4 choices to the patient “ Not at all,” 
“Several days,” “More than half the days,” and “Nearly everyday”. 
Tick the appropriate response. 
 
g. Question g: “Over the last 2 weeks how often have you had trouble 
concentrating on things, such as reading the newspaper or 
watching tv” and read the 4 choices to the patient “ Not at all,” 
“Several days,” “More than half the days,” and “Nearly everyday”. 
Tick the appropriate response. 
 
h. Question h: “Over the last 2 weeks how often have you been 
moving or speaking so slowly that other people have noticed, or 
had the opposite where you were so fidgety or restless that you 
have been moving around a lot more than usual” and read the 4 
choices to the patient “ Not at all,” “Several days,” “More than half 
the days,” and “Nearly everyday”. Tick the appropriate response. 
 
i. Question i: “Over the last 2 weeks how often have you had 
thoughts that you would be better off dead or of hurting yourself” 
and read the 4 choices to the patient “ Not at all,” “Several days,” 


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“More than half the days,” and “Nearly everyday”. Tick the 
appropriate response. 
 
i. NOTE: if the patient expresses suicidality and/or scores very 
highly on the PHQ9, please ensure that she has talked to 
another clinic staff member (counselor, RN, NP, MD) about 
this so that she can be referred to adequate resources.  
 
23.  Ask the patient to assess her pain currently on a scale of 0-10. Show her 
the 0-10 scale on Form 1 and read the question as printed on the Form. 
Ask her to select the appropriate box on the scale. Mark an “X” in the 
appropriate box, based on her response.  
 
24. Ask the patient how acceptable this amount of pain was to her. Read the 5 
response choices to the patient: “Very acceptable”, “Somewhat 
Acceptable”, “Somewhat Unacceptable”, or “Very Unacceptable”. Tick the 
appropriate response. If the patient is unable to answer the question, tick 
“Don’t know”. 
 
25.  Ask the patient if she is experiencing any nausea right now. If she is not 
experiencing nausea currently, circle “None” on the corresponding line. If 
she is experiencing nausea, ask her if it was mild, moderate, or severe 
and circle her response. If the woman would like the study staff to define 
mild, moderate or severe, read her the definitions below. These definitions 
are also printed directly on Form 1: 
 
26. Indicate whether the patient has experienced any nausea in the past week 
by checking “Yes” or “No”.  
 
27. Indicate whether the patient has experienced any vomiting in the past 
week by checking “Yes” or “No”.  
 
Items 28-37 can be completed by gathering information for the patient’s chart. 
Thus the patient interview is completed after Item 27 is completed, unless the 
Mild: Symptoms were annoying but did not get in the way of your usual 
activities. 
 
Moderate: Symptoms got in the way as you tried to do your usual activities 
but you were still able to do most of the things you needed to. 
 
Severe: Symptoms stopped you from being able to do your usual 
activities. 


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IRB-approved study staff is unable to access the patient’s chart, in which case 
the staff can refer to the clinician or physician to complete items 28-37.  
 
28. Record the patient’s age in years. 
 
29. Record the patient’s BMI 
 
30. Record the patient’s Biparietal Diameter (BPD) as assessed by the 
ultrasound performed earlier in the participant’s appointment on Day 1. 
Record the BPD in cm to two decimal places.  
 
31. Record the patient’s GA as charted in the clinic in weeks and days. Use 
the main gestational age that the clinic uses when documenting this 
patient.  
 
32. Participants will be divided into two study groups based on gestational 
age. For participants whose BPD is measuring 4.61-5.24cm check “Group 
1”. For participants whose BPD measures 5.25-5.88cm, check “Group 2”.  
 
a. Note that FPA Women’s Health locations in Los Angeles and Long 
Beach will only be recruiting patients for Group 1. Thus all patients 
enrolled in these sites should have BPD within 4.61-5.24cm, and 
should all be checked for Group 1. 
 
33.  This question assesses the patient’s reason for her current abortion. This 
question should be completed in consultation with a counselor or with a 
clinician or physician. If the patient is having her abortion for a fetal 
anomaly or a pregnancy complication check “Anomaly/comp.”. If the 
patient is having her abortion for any other reason, check “Other”.  
 
a. Patients with cranial defects must be between 20w0d and 24w0d 
by best estimate of gestational age AND BPD must also be within 
range above. If cranial defects preclude BPD measurement, use 
the best composite sonographic dating criteria available to ensure 
the patient is between 20w0d and 24w0d. If accurate dating is 
unable to be obtained, the patient is not eligible for the study. 
b. Other kinds of fetal anomalies (non-cranial defects, see above a.) 
are otherwise eligible for the study. 
 
34. Record the total number of times the patient has been pregnant, 
regardless of outcome. A multi-gestational pregnancy is 1 pregnancy. 
Include her current pregnancy in this total.  
 


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35. Record the total number of vaginal deliveries this patient has had. Delivery 
of a multi-gestational pregnancy is 1 delivery. Vaginal deliveries are 
considered deliveries occurring >20wks. 
 
36. Record the total number of c-section deliveries this patient has had. 
Delivery of a multi-gestational pregnancy is 1 delivery. 
 
37. Record the number of abortions the patient has had. An abortion is 
considered to be any elective termination of a pregnancy. 
 
38. Record the number of miscarriages the patient has had. 
 
39. Check any of the medical conditions listed that the patient has recorded in 
her chart. If there is a medical condition that the patient has or previously 
had that is not listed, check “Other” and write in the medical condition as 
it’s listed in her chart.  
 
a. NOTE: anxiety that is listed in the chart as a chronic condition (i.e. 
has been diagnosed by a healthcare professional and/or uses 
medication to manage) then this should be considered “psychiatric 
disease”. If the chart notes that the patient is generally feeling 
anxious (for example, is feeling anxious about the abortion 
procedure), this does not need to be noted. 
 
This is the end of Form 1: Eligibility Screening and Baseline Data, Day 1. 
Upon completion of Form 1, study staff should: 
 Review Form 1 for accuracy and completeness 
 Make corrections as necessary. Date and initial all corrections. 
 Sign both sides of the Form in the header (next to “Staff signature”) 
 Once clinician/physician has completed H&P with patient, confirm 
eligibility criteria with clinician/physician and have physician sign Form 1 
under “Clinician signature) 
 Proceed to Randomization, Drug Tracking Log, Drug Drawing 
 When patient is taken to room for dilator placement and injection, proceed 
to Form 2: Dilator and Injection Data, Day 1 
 


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B. Form 2: Dilator and Injection Data, Day 1  
 
Form 2 Overview 
 
Form 2 is used to document the injection of the study medication and dilator 
placement. It also assesses the pain felt by the patient during the dilator 
placement and injection. This form will be completed by IRB-approved study staff 
before and after the injection and during dilator placement. The staff member will 
survey both the provider and the participant while completing.  
 
Injection and dilator order will vary by site. LOVEJOY: Injection will happen first, 
followed by dilator placement. FPAWH: Dilators will be placed first, followed by 
injection. SFGH: Order may vary. 
 
The Injection Questionnaire and the Dilators Questionnaire should be asked and 
answered about the specific event to which they refer (injection or dilator 
placement). Please perform the questionnaires DIRECTLY after each event and 
clarify for the participant that the questions are referring to that event only. 
 
Form 2 Detailed Instructions 
 
Injection data on Form 2: 
 
Write the participants Randomization ID in the box provided. The randomization 
ID contains the group assignment code 1 or 2 followed by the site specifier (1 for 
SF, 2 for LJ, 3 for LA, 4 for LB) and the patient-specific number (01, 02, 03). For 
example, a Group 1 participant from SF would have the Randomization ID 1-101. 
Summary of Randomization IDs: 
• First number = GA group (1= BPD 4.61-5.24cm, 2= BPD 5.25-5.88cm) 
• Dash 
• Second number = site (SFGH = 1, Lovejoy = 5-6, FPAWH Los Angeles = 3, 
FPAWH Long Beach = 4) 
• Third and fourth numbers go in numerical order starting at 01 for each site and 
group 
 
Women’s Options Center, 
San Francisco CA 
Lovejoy Surgicenter, 
Portland OR 
FPAWH, Los 
Angeles CA 
FPAWH, Long 
Beach CA 
1-101 
2-101 
1-501 
2-501 
1-301 
1-401 
1-102 
2-102 
1-502 
2-502 
1-302 
1-402 
1-103 
2-103 
1-503 
2-503 
1-303 
1-403 
1-104 
2-104 
1-504 
2-504 
1-304 
1-404 
 


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For FPA Women’s Health locations, only participants in the first gestational age 
group 1 (BPD 4.61-5.24) are being recruited. Thus all randomization numbers will 
begin with “1-“.  
 
Blinded injection preparation and placement 
Injection drug preparation and randomization protocol vary by site. See below for 
the protocols of each site: 
 
SF: Women’s Options Center  
WHO draws up study medication: 
- 
The RA will fax down a Pharmacy Order form to the ZSFG Pharmacy 
once the patient is enrolled.  
- 
A pharmacist who is not involved with any other study procedures will 
draw up the study drug (digoxin or placebo) based on the randomization 
scheme.  
- 
The pharmacist will then tube the labeled syringe (containing either 
digoxin or placebo) up to 6G. 
 
Randomization protocol: 
- 
The pharmacist will use the subject ID number located on the faxed 
Pharmacy Order form to look at the randomization guide to determine 
whether the patient will receive active drug (digoxin) or placebo.  
- 
Once the injection is administered, the participant is considered 
randomized. Any participant who withdraws from the study prior to the 
injection is not randomized and the randomization number can be reused. 
The unused syringe will be disposed.   
 
Drug Preparation 
- 
Once the pharmacist determines whether the patient will receive digoxin 
or placebo he/she will do the following: 
o If digoxin, the pharmacist will retrieve two ampules digoxin (500 
mcg/2 mL concentration) from study binder in IVAC 
o If placebo, the pharmacist will retrieve a 10 ml vial of 0.9% sodium 
chloride (use general IVAC stock) 
- 
The pharmacist will aseptically draw up 4 mL of product into a 5 mL 
syringe 
- 
The pharmacist will label the syringe using the pre-made labels found in 
the study binder and place the syringe in a protect-from-light bag. 
 
LJ: Lovejoy Surgicenter 
 
WHO draws up study medication: 
- 
A Lovejoy Surgicenter nurse (RN) from the upstairs section of the center 
(clinical section) who is not part of the patient’s further care will draw up 
after the patient is enrolled.  


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- 
The RA is responsible for informing the nurse of the patient and 
coordinating with the nurse so he/she can prepare the drug prior to the 
injection. 
- 
The nurse who is responsible for drawing up the medication may change 
per participant as each nurse is assigned certain patients and not involved 
in the care of others. The nurse will be recruited to draw up medication 
only of the patients he/she is not otherwise caring for. If he/she is caring 
for a study participant, he/she may draw up the drug for another study 
participant but not for his/her participant patient. 
 
Randomization protocol: 
- 
Prior to the study starting, the coordinating center (UCSF) will send a 
randomization list that is developed to be consistent with the 
randomization schemes of the other sites.  
- 
Using this randomization list, research assistants who are not otherwise 
related to the study (research assistants known to the clinic but in different 
departments or on different studies) will create envelopes that correspond 
to each randomization ID.  
- 
Each envelope will be labeled with only a Randomization ID and inside the 
sealed envelope will be the drug randomization: “Placebo” or “Digoxin” 
- 
This envelope is opened only by the nurse who will be drawing up the 
drug and the contents are not to be shown to anyone else. 
- 
Once the envelope is opened, the participant is considered randomized. 
Any participant who withdraws from the study prior to envelope opening is 
not randomized and the envelope is replaced in the cabinet to be reused. 
Any envelope that is open is discarded even if the participant does not 
ultimately received the injection and that randomization ID is not reusable. 
- 
Thus it is important that the envelope be opened, and study drug drawn, 
as close to the injection as possible. 
- 
Envelopes will be kept in a locked box in the clinic 
 
Drug Preparation 
- 
Once they have opened the envelope, the nurse responsible for drawing 
up the medication should prepare the injection syringe out of view of any 
other research or clinic staff. The drug may be prepared downstairs, 
where staff are not involved in clinical care, or anywhere that is not in the 
presence of any one else caring for the study participant.  
- 
No drug containers other than the syringe containing the prepared 
medication should be brought into the procedure room during the injection 
to ensure blinding. 
 
FPAWH – LA and LB sites:  
WHO draws up study medication: 
- 
A FPAWH medical assistant (MA) who is not part of the patient’s medical 
care will draw up the study medication (digoxin or placebo) after the 
patient is enrolled.  


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- 
When the study medication is prepared, the MA will deliver the syringe on 
a tray to the nurse who is performing the injection.  
 
Randomization protocol: 
- 
Prior to the study starting, the coordinating center (UCSF) will send a 
randomization list that is developed to be consistent with the 
randomization schemes of the other sites.  
- 
Once a patient is enrolled, the RA will inform the MA of the patient’s 
randomization number and the MA will use the randomization list 
(contained in an envelope) to determine if placebo or digoxin should be 
drawn up. The MA who draws up the study drug is the only one who has 
access to this envelope. 
- 
Once the injection is administered, the participant is considered 
randomized. Any participant who withdraws from the study prior to the 
injection is not randomized and the randomization number can be reused. 
The unused syringe will be disposed.   
 
Drug Preparation 
- 
Once the randomization list is viewed, the MA responsible for drawing up 
the medication should prepare the injection syringe out of view of any 
other research or clinic staff. The drug is usually prepared in the recovery 
room, where staff are not involved in clinical care, or anywhere that is not 
in the presence of any one else caring for the study participant.  
- 
No drug containers other than the syringe containing the prepared 
medication should be brought into the procedure room during the injection 
to ensure blinding. 
 
 
 
1. Record today’s date. Dates should be recorded as month/day/year 
(MM/DD/YYYY) 
 
2. Record pain medications given before injection and dilator placement. 
--- FPAWH skip to dilator placement and then items 10-16. After question 16 
return to item 3 and proceed with the rest of the form.--- 
 
3. Record whether the patient was randomized. If they received the blinded 
injection, check “Yes” indicating they were randomized. If they did not 
receive the blinded injection, check “No” indicating they were not 
randomized.  
 
a. If they were not randomized, indicate the reason(s) for not 
randomizing the patient on the line provided. 
b. For LJ: the patient is considered randomized if their envelope was 
opened even if they didn’t receive the injection. 


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4. Print the last name of the clinician or physician administering the injection 
on the line provided. 
 
5. Record the time that the injection was completed and circle “AM” or “PM”. 
Record the time as standard time (12hr format), hh:mm. No stopwatch is 
needed. Injection is considered complete when all study medication has 
been administered. 
 
Directly after the injection procedure is complete, ask the patient items 6-9.  
 
6.  Ask the patient to assess her pain specifically during her injection on a 
scale of 0-10. Show her the 0-10 scale on Form 2 and read the question 
as printed on the Form. Ask her to select the appropriate box on the scale. 
Mark an “X” in the appropriate box, based on her response. 
 
7.  Ask the patient how acceptable this amount of pain was to her. Read the 
5 response choices to the patient: “Very acceptable”, “Somewhat 
Acceptable”, “Somewhat Unacceptable”, or “Very Unacceptable”. Tick the 
appropriate response. If the patient is unable to answer the question, tick 
“Don’t know”. 
 
8.  Ask the patient how the injection compared to her expectations prior to 
the procedure. Read her the 3 answer choices “Better than expected”, 
“The same as expected”, “Worse than expected” and tick the appropriate 
response. If the patient is unable to answer the question, tick “Don’t 
know”.  
 
9. Ask the patient if she is experiencing any nausea right now. If she is not 
experiencing nausea currently, circle “None” on the corresponding line. If 
she is experiencing nausea, ask her if it was mild, moderate, or severe 
and circle her response. If the woman would like the study staff to define 
mild, moderate or severe, read her the definitions below. These definitions 
are also printed directly on Form 2: 
 
Mild: Symptoms were annoying but did not get in the way of your usual 
activities. 
 
Moderate: Symptoms got in the way as you tried to do your usual activities 
but you were still able to do most of the things you needed to. 
 
Severe: Symptoms stopped you from being able to do your usual 
activities. 


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Osmotic dilator placement occurring during Form 2 
Osmotic dilators should only be placed by clinicians specified in the Delegation of 
Authority Log. 
Items 10-16 should be recorded by study staff during the dilator placement. 
 
10. Record whether the dilators were placed in the patient’s cervix prior to her 
study drug injection or after by checking “Before” and “After” 
 
11. Record the number of Laminaria dilators and the number of Dilapan 
dilators successfully placed in the cervix. 
 
12. Record the time that dilator placement was completed and circle “AM” or 
“PM”. Record the time as standard time (hr format), hh:mm. No stopwatch 
is needed. 
 
13. Indicate whether adjunctive mifepristone was given after dilator placement 
by checking “Yes” or “No”.  
 
14. Indicate whether the amniotic sac was ruptured during dilator placement 
by checking “Yes” or “No”. 
 
Once the dilator placement is complete, ask the patient questions 15-16, rating 
her pain during dilator placement. Ask these questions while the patient is still in 
the procedure room. 
 
15.  Ask the patient to assess her pain specifically during her dilator 
placement on a scale of 0-10. Show her the 0-10 scale on Form 2 and 
read the question as printed on the Form. Ask her to select the 
appropriate box on the scale. Mark an “X” in the appropriate box, based 
on her response. 
 
16.  Ask the patient how acceptable this amount of pain was to her. Read the 
5 response choices to the patient: “Very acceptable”, “Somewhat 
Acceptable”, “Somewhat Unacceptable”, or “Very Unacceptable”. Tick the 
appropriate response. If the patient is unable to answer the question, tick 
“Don’t know”. 
 
After the procedures are complete ask the clinician the following three questions. 
Make sure to ask these questions not in the presence of the patient (aka once 
the patient or clinician has left the procedure room).  
 


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17. Once the injection is complete, record where the administering clinician 
thinks the injection went by checking “Intra-amniotic”, “Thorax”, “Cardiac”, 
“Extremity”. If the physician responds with another location, check “Other”. 
 
18. Ask the clinician of their confidence in their response to Item 17 and 
record their response by checking “Confident” or “Not confident”. 
 
19.  Ask clinician how difficult the injection was and record their response as 
“very easy”, “somewhat easy”, “somewhat difficult”, or “very difficult:. 
 
 
 
This is the end of Form 2: Dilator and Injection Data, Day 1. Upon completion 
of Form 2, study staff should: 
 Review Form 2 for accuracy and completeness 
 Make corrections as necessary. Date and initial all corrections. 
 Sign both sides of the Form in the header (next to “Staff signature”) 
 If Form 1 was not already completed, review patient’s chart and complete 
any missing data from Form 1 
 Ensure that the patient received $50 payment and that this payment is 
logged in the Payment Log. 
 The next data collection form to be completed will be Form 3: Arrival 
Data, Day 2. Form 3 must be completed when the patient arrives at the 
clinic on Day 2. 
 


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C. Form 3: Arrival Data, Day 2  
 
Form 3 Overview 
 
Form 3 is used to assess the patient’s experience of any side effects or adverse 
events since she was last seen in the clinic on Day 1. Form 3 will also document 
any pain the patient is having currently. Form 3 should be completed when the 
patient arrives to clinic on Day 2.  
 
Form 3 Detailed Instructions 
 
1. Record today’s date. Dates should be recorded as month/day/year 
(MM/DD/YYYY).  
 
2. Take the patient’s temperature as soon as possible after she arrives in the 
clinic. Record the patient’s temperature in degrees Fahrenheit.  
 
3. Ask the patient if she has experienced the following symptoms since she 
left clinic yesterday: Nausea, vomiting, chills, fever, dizziness. If she did 
not experience the symptom, circle “None” on the corresponding line. If 
she did experience the symptom, ask her if it was mild, moderate, or 
severe and circle her response. If the woman would like study staff to 
define mild, moderate, or severe, read her the definitions below. These 
definitions are also printed directly onto Form 3: 
 
4. Ask the patient if they took any narcotics for pain since leaving the clinic 
yesterday. If they need further examples, read the examples listed “Norco, 
tyco or T3, Percocet, Vicodin”. If they have taken a narcotic since leaving 
the clinic yesterday, check “Yes” and print the medication name. If they 
haven’t taken any narcotics, check “No”. 
 
5. Ask the patient if they took any other medication for pain since leaving the 
clinic yesterday. If they need further examples, read the examples listed 
Mild: Symptoms were annoying but did not get in the way of your usual 
activities. 
 
Moderate: Symptoms got in the way as you tried to do your usual activities 
but you were still able to do most of the things you needed to. 
 
Severe: Symptoms stopped you from being able to do your usual 
activities. 


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“ibuprofen, tylenol”. If they have taken any other medications for pain 
since leaving the clinic yesterday, check “Yes” and print the medication 
name. If they haven’t taken any other medications, check “No”. 
 
6. Ask the patient if they took any medication for nausea since leaving the 
clinic yesterday. If they have taken any medications for nausea since 
leaving the clinic yesterday, check “Yes” and print the medication name. If 
they haven’t taken any other medications, check “No”. 
 
7. Ask the patient if they called the clinic for any reason since leaving the 
clinic yesterday. If they have called the clinic check “Yes” and print the 
reason for their call. If they haven’t taken any other medications, check 
“No”. 
 
8. Ask the patient if they went to an Emergency Room or any other clinic for 
any reason since leaving the clinic yesterday. If they did go to an 
Emergency Room or another clinic check “Yes” and print the reason for 
their visit. If they haven’t taken any other medications, check “No”. 
 
9. Ask the patient what their bleeding has been like since leaving the clinic 
yesterday. Read them the question as printed followed by the following 4 
responses: “No bleeding”, “Spotting or light bleeding only”, “Moderate 
bleeding (like a period)”, or “Heavy bleeding (heavier than a bleeding)”. 
Tick the appropriate response.  
 
10. Ask the patient if they noticed the fetus had stopped moving?. If they say 
yes, check “Yes” and record the approximate time they last felt fetal 
movement if they can remember. Record the time in 12hr format, as 
hh:mm and circle AM or PM. If they don’t remember, write “99:99”. If they 
have not felt any stop in fetal movement, check “No”.  
 
11. Ask the patient which medication they think they received yesterday. 
Check the appropriate response and write why they think they received 
that particular medication. If the participant cannot offer a guess of which 
medication she received check “Don’t Know”.  
 
12. Ask the patient to assess her pain currently on a scale of 0-10. Show her 
the 0-10 scale on Form 3 and read the question as printed on the Form. 
Ask her to select the appropriate box on the scale. Mark an “X” in the 
appropriate box, based on her response.  
 
13. Ask the patient how acceptable this amount of pain was to her. Read the 5 
response choices to the patient: “Very acceptable”, “Somewhat 


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Acceptable”, “Somewhat Unacceptable”, or “Very Unacceptable”. Tick the 
appropriate response. If the patient is unable to answer the question, tick 
“Don’t know”. 
 
14. After the patient questionnaire is completed, refer to the patient’s medical 
chart. Check “yes” or “no” to reflect whether misoprostol was given 
adjunctively. 
 
a. If checked “Yes”, provide the time in HH:MM (12hr format) and 
circle AM or PM. Record the dose in micrograms and report the 
route of drug delivery by checking “Buccal”, “Oral” or “Other”. If 
choosing other record the route used. 
 
15. Check “yes” or “no” to reflect whether the patient was given any other 
medications after arrival at the clinic and before the procedure (like 
ibuprofen, morphine, Zofran, Ativan, norco, etc). 
 
a. If checked “yes”, please list the medications given. 
 
This is the end of Form 3: Arrival Data, Day 2. Upon completion of Form 3, 
study staff should: 
 Review Form 3 for accuracy and completeness 
 Make corrections as necessary. Date and initial all corrections. 
 Sign both sides of the Form in the header (next to “Staff signature”) 
- 
Proceed to Form 4: Intra-operative Data, Day 2, which must be 
completed during her abortion procedure. 


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D. Form 4: Intra-operative Data, Day 2 
 
Form 4 Overview 
 
Form 4 is used to document the initial pre-operative setup, procedure time, and 
details of the D&E procedure. Form 4 will also include the operating physician’s 
assessment of procedure difficulty and his or her guess as to the study drug 
assignment. Questions from Form 4 should be completed in consultation with the 
operating physician. The operating physician must be listed on the Delegation of 
Authority Log as approved to perform the D&E.  
 
Form 4 Detailed Instructions 
 
1. Record today’s date. Dates should be recorded as month/day/year 
(MM/DD/YYYY).  
 
2. Print the last name of the clinician or physician performing the D&E on the 
line provided. 
 
3. Record what anesthesia the patient received during their abortion 
procedure by checking the appropriate response.  
 
a. Moderate sedation is defined as “a drug-induced depression of 
consciousness during which patients respond purposefully to verbal 
commands, either alone or accompanied by light tactile stimulation. 
No interventions are required to maintain a patent airway, and 
spontaneous ventilation is adequate. Cardiovascular function is 
usually maintained” per ASA guidelines 
4. Prior to the MD placing their speculum and starting to the procedure, the 
RN assisting with ultrasound during the procedure will check for fetal 
presentation and cardiac activity using the ultrasound. The MD is blinded 
and CANNOT know whether or not cardiac activity is present. The 
study RA must remain blinded to cardiac activity as well. The MD 
must be turned around and not looking at the ultrasound. The RN may 
inform the MD about fetal presentation but will not say whether or not 
there was cardiac activity aloud.  
 
A separate log, the Cardiac Activity Log, will be used to record 
cardiac activity. RN will record the subject’s enrollment ID, the date, 
cardiac activity (yes, no, or unsure) and initials. The Cardiac Activity Log 
will be kept in an opaque folder, and the research assistant will remain 
blinded to the cardiac activity. 
 


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5. Based on the findings of the RN performing the ultrasound, record the 
fetal presentation by ticking “Cephalic”, “Breech” or “Transverse”. If the 
fetal presentation is not listed in the response choices, tick “Other” and 
write in the fetal presentation on the line provided.  
 
After the RN is done viewing cardiac activity, it may be necessary for the clinician 
to view the ultrasound during the procedure. This is acceptable as necessary for 
the procedure, however the physician should avoid intentionally searching for 
cardiac activity to the degree that is possible. 
 
6. Using a clock, record the time when the speculum is first placed in the 
vagina. Record the time as standard time (12hr format) hh:mm. Circle AM 
or PM as appropriate. Start the stopwatch at this time.  
 
7.  
a. The initial amount of cervical dilation will be measured using 
Bierers or ring forceps. Record which instrument the clinician uses 
to measure cervical dilation by checking either “ring forceps” or 
“Bierer forceps”. (Preference is ring forceps) 
b. The clinician will place the Bierers or ring forceps into the internal 
os of the cervix and open them as far as possible. The research 
assistant will use a paper ruler to measure the distance between 
the handles and will record the distance in millimeters in the spot 
marked “distance between handles”.  
c. LATER when the clinician has finished using the instrument that 
was used to check the dilation (Bierers or ring forceps), the 
research assistant will open them to the same distance (using the 
ruler to match the distance between the handles to the original 
distance between the handles in mm) and keeping the handles at 
the original distance, will record the distance between the tips of the 
instrument in millimeters in the spot marked “distance between 
tips”. This should be done after the procedure is over when the 
clinician is no longer using this instrument. 
 
8. Record the time on the stopwatch when the first instrument enters the 
uterus. Record the time as seen on the stopwatch, hh:mm:ss. Do not reset 
or pause the stopwatch. The first instrument could be Bierer forceps, a 
mechanical dilator, or the suction cannula. 
 
9. Indicate whether the physician had to mechanically dilate the cervix before 
beginning the procedure by checking “Yes” or “No”.  
 


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10. Record the procedure end time on the stopwatch when the last instrument 
is removed from the uterus. Record the time as seen on the stopwatch, 
hh:mm:ss. Do not reset or pause the stopwatch. 
 
11. Indicate whether bimanual massage, compression or uterus elevation to 
control bleeding following the abortion procedure by checking “Yes” or 
“No”.  
 
12. Indicate whether Monsel’s solution or Silver Nitrate was used to stop any 
bleeding following the abortion procedure by checking “Yes” or “No”. 
 
13. If the patient is having an IUD contraceptive placed following her abortion 
procedure, check “Yes” 
 
a. Record the time on the stopwatch when the IUD package was 
requested by the physician, with the format hh:mm:ss.  
 
b. IF, following IUD placement, the strings are cut, record the time the 
strings are cut, with the format hh:mm:ss. If the IUD is left in place, 
move to item 13, leaving “Time to removal” empty. 
 
c. IF, following IUD placement, the IUD is subsequently removed, 
record the time of removal, with the format hh:mm:ss. If the strings 
were never cut during the IUD placement, leave “Time to strings 
cut” empty. 
 
d. If the patient did not have an IUD placed check “No”. 
 
e. Do not reset or pause the stopwatch 
 
14.  If the patient had a cervical laceration with repair during her abortion 
procedure check “Yes”. 
 
a. Record the time on the stopwatch when the cervical laceration 
repair begins, with the format hh:mm:ss. 
 
b. Record the time on the stopwatch when the cervical laceration 
repair is finished, with the format hh:mm:ss 
 
c. If the patient did not have a cervical laceration during her abortion 
procedure, check “No”. 
 


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15.  Record whether any uterotonics were used after the procedure, while the 
patient was still in the procedure room, by checking “Yes” and writing the 
name, dose and time administered (as indicated on the stopwatch in the 
format hh:mm:ss) or checking “No” if no uterotonics were used. 
 
a. At Lovejoy and FPAWH sites, please record Pitocin (and the dose) 
as an intra-operative uterotonic. You can record the time of day 
given from the chart, and it will always be “prophylactic” 
b. Record any uterotonics that are used in the procedure room, even if 
the speculum has been removed, on Form 4. 
c. Record any uterotonics used once the patient has left the 
procedure room (once in the recovery room) on Form 5. 
 
16. Once all the instruments are removed from the vagina, including the 
speculum and MD’s fingers, stop the stopwatch and record the time in the 
format hh:mm:ss.  
 
17. Record any complications that occurred during the procedure by checking 
the appropriate complication on the list provided.  
 
a. If she experienced no complications check “None” 
 
b. If she required placement of a Foley or Bakri for bleeding 
tamponade while still in OR after procedure, check “Foley/Bakri”. 
 
c. If she required vaginal packing room for hemostasis, check “Vag 
pack.”  
 
d. If she required am immediate blood transfusion (while in OR for 
procedure) check “Transfusion.”  
 
e. If she required a reaspiration of uterine contents after all 
instruments were removed from the vagina, but while she was still 
in the procedure room, check “Reaspiration-immediate”. 
 
f. If she experiences a uterine perforation during her procedure, 
check “Perforation”.  
 
g. If she experienced a complication that is not listed, check “Other” 
and write the complication on the line provided (ex. Major surgery). 
Receiving uterotonics does not qualify as a complication. 
 
18. Record the estimated blood loss in milliliters. 


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19. For Site SF: Record the measured blood loss in milliliters, per clinic 
protocol 
 
Once the physician has finished his or her work with the patient, ask them to 
complete items 21-24. 
 
20. Ask the operating physician whether the patient’s membranes were intact 
or if there was rupture of membranes prior to starting the D&E. Record 
their response by checking “Yes” or “No”.  
 
21.  Ask the operating physician to assess the overall procedure difficulty. Tick 
the appropriate response: “Very easy”, “Somewhat easy”, “Somewhat 
difficult”, “Very difficult”.  
 
22. Ask the operating physician their reasoning for their answer to item 22 and 
write their response on the line provider. 
 
23. Ask the operating physician whether the blood loss during the procedure 
was “less than normal”, “normal” or “more than normal” compared to 
his/her typical D&E procedure of similar gestational age.  
 
24. Ask the operating physician whether they were concerned about the blood 
loss following the procedure. Record their response by checking “Yes” or 
“No”.   
 
25.  Ask the operating physician to guess the patient’s study assignment. Tick 
the box “Digoxin” or “Placebo” and write their reasoning on the line 
provided. If the operating physician is uncertain about the patient’s study 
assignment tick “Don’t know”.  
 
a. If the physician guessed digoxin, ask whether they believed there 
was fetal demise prior to the procedure and ask how that demise 
affected the procedure. Record their response on the line provided. 
 
26. Ask the operating physician if in general, not just during this current 
abortion procedure, whether they find it easier to do an abortion procedure 
when the fetus is demised. Check “Easier”, “The Same”, or “Harder” as 
appropriate. 
 
This is the end of Form 4: Intra-operative Data, Day 2. Upon completion of 
Form 4, study staff should: 
 Review Form 4 for accuracy and completeness 


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 Make corrections as necessary. Date and initial all corrections. 
 Sign both sides of the Form in the header (next to “Staff signature”) 
- 
The next data collection form to be completed will be Form 5: Post-
Operative Data, Day 2. 


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E. Form 5: Post-Operative Data, Day 2.  
 
Form 5 Overview 
 
Form 5 is a survey of the patient’s experiences after her abortion procedure, 
including her pain, side effects and satisfaction.  
 
Form 5 Detailed Instructions 
 
1. Record today’s date. Dates should be recorded as month/day/year 
(MM/DD/YYYY).  
 
2. Ask the patient to assess her pain currently on a scale of 0-10. Show her 
the 0-10 scale on Form 5 and read the question as printed on the Form. 
Ask her to select the appropriate box on the scale. Mark an “X” in the 
appropriate box, based on her response.  
 
3. Ask the patient how acceptable this amount of pain was to her. Read the 5 
response choices to the patient: “Very acceptable”, “Somewhat 
Acceptable”, “Somewhat Unacceptable”, or “Very Unacceptable”. Tick the 
appropriate response. If the patient is unable to answer the question, tick 
“Don’t know”. 
 
4.  Ask the patient if she has experienced the following symptoms since she 
left clinic yesterday: Nausea, vomiting, chills, fever, dizziness. If she did 
not experience the symptom, circle “None” on the corresponding line. If 
she did experience the symptom, ask her if it was mild, moderate, or 
severe and circle her response. If the woman would like study staff to 
define mild, moderate, or severe, read her the definitions below. These 
definitions are also printed directly onto Form 5: 
 
5. Ask the patient how satisfied they are with their abortion procedure 
overall. Read the choices “Very satisfied”, “Somewhat satisfied”,  , 
Mild: Symptoms were annoying but did not get in the way of your usual 
activities. 
 
Moderate: Symptoms got in the way as you tried to do your usual activities 
but you were still able to do most of the things you needed to. 
 
Severe: Symptoms stopped you from being able to do your usual 
activities. 


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“Somewhat unsatisfied” and “Very unsatisfied”. Record their response by 
checking the appropriate box. 
 
6. Ask the patient how satisfied they are with specifically their injection 
procedure overall. Read the choices “Very satisfied”, “Somewhat 
satisfied”, “Somewhat unsatisfied” and “Very unsatisfied”. Record their 
response by checking the appropriate box. 
 
7. Ask the patient if she were to become pregnant in the future and need a 
second trimester abortion similar to her procedure today, would she prefer 
to get the digoxin injection or not have the injection. Record whether she 
would rather have the injection, not have the injection or not sure by 
checking the appropriate box. Record the reason for her response on the 
line provided. 
 
8. Ask the patient if they would recommend the digoxin injection to other 
women having a second trimester abortion. Record whether she would 
recommend having the injection or not having the injection, or whether she 
is not sure, by checking the appropriate box. Record the reason for her 
response on the line provided. 
 
Item 8 is the final question for the patient. Once she has completed the 
questionnaire, provide the patient with the remaining $50 payment and log it in 
the Payment Log. At that point the patient has completed her participation in the 
study and is free to leave after she has been cleared for discharge by the clinic 
staff. The study staff should complete the rest of Form 5 by consulting the 
patient’s chart or clinic physicians. 
 
9. Record whether any uterotonic medications were given to the patient in 
the recovery room following her abortion procedure. If she was given 
uterotonics, check “Yes” and record the name, dose and time given (in 12-
hr standard format, hh:mm, and circle AM or PM appropriately). If no 
uterotonic medication was given check “No”.  
 
10.  Record the time the patient was discharged from the clinic. Record the 
time in standard format (12-hr format), hh:mm. Circle AM or PM as 
appropriate. 
 
11.  Record any post-procedure complications. These are complications that 
occurred AFTER the patient has been taken out of the OR immediately 
following the procedure. 
 
a. If she experienced no complications check “None” 


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b. If she required placement of a Foley or Bakri for bleeding 
tamponade and was taken back into the OR for placement, check 
“Foley/Bakri – brought back in OR”. 
 
c. If she required vaginal packing room for hemostasis and was taken 
back into the OR for placement, check “Vag pack – back in OR.”  
 
d. If she required am immediate blood transfusion after the procedure 
finished and patient was out of OR, check “Transfusion – post-
procedure.”  
 
e. If she required a Uterine Artery Embolization (UAE), check 
“Embolization.” 
 
f. If she required a reaspiration of uterine contents after leaving the 
procedure room (has to return to procedure room, OR or get 
admitted to hospital), check “Reaspiration- Brought back to OR”. 
 
g. If she is admitted to a hospital following her procedure, check 
“Admission to hospital”. 
 
h. If she experienced any other post-procedure complication that is 
not listed, check “Other” and write the complication on the line 
provided (ex. Major surgery). Receiving uterotonics does not qualify 
as a complication. 
 
This is the end of Form 5: Post-operative Data, Day 2. Upon completion of 
Form 5, study staff should: 
 Review Form 5 for accuracy and completeness 
 Make corrections as necessary. Date and initial all corrections. 
 Sign both sides of the Form in the header (next to “Staff signature”) 
 Ensure that the subject received the $50 payment and that this was 
logged in the Payment Log. 
This is the end of the data collection. 


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VI. STUDY LOGS 
 
A. Recruitment and Enrollment Log 
The Recruitment and Enrollment Logs are electronic files used to record the 
progress of the study participants. Each site will have its own R&E Log and will 
email the updated R&E log to the coordinating site every week. The title of the 
R&E document should be changed to reflect the appropriate week before it is 
sent to the coordinating site (e.g. Enrollment Log_LJ_12.7.16 -> Enrollment 
Log_LJ_12.14.16). 
 
Recruitment Log 
The Recruitment log is used to record the total number of possible participants at 
each clinic and the number who were actually approached. It also monitors their 
reason for declining participation and ineligibility. In the first column, Column A, 
the weeks are listed. Each row corresponds to a single recruitment day, or Day 1. 
Record the date of that Day 1 in Column B next to the week. 
• Based on the clinic schedule, which differs per site, periodically update the 
recruitment log with the number of patients who come to clinic for D&E as 
the day goes on.   
o Recruitment days (Day 1) are as follows: 
 SF: Tuesdays, Thursdays 
 LB: Mondays 
 LA: Wednesdays, (possibly Fridays) 
 LJ: Monday, Tuesday, Wednesday, Thursday 
 
• Not approached: Based off of how many patients present to the clinic by 
the end of each recruitment day, record how many were not approached 
under “NOT Approached”. In the next column, record the reason they 
were not approached for the study. Reasons for not approaching include: 
o Being found ineligible prior to approaching: wrong gestational age 
(BPD <4.61 or >5.88; also at FPAWH if they were >5.24); under 18 
years old, non-English or Spanish speaking; if it was a multiple 
gestation pregnancy; if they’re incarcerated; per clinical judgment, 
when a nurse, physician or other clinic staff requests that the 
patient not be approached (i.e. mentally unstable, emotional, etc) 
though reason may not always be provided. 
 For LJ and both FPAWH sites: Spanish-speaking patients 
are not being recruited so indicate this an appropriate 
reason.  
o Missed the opportunity to approach the patient: RA was not 
available/with another participant; clinic flow was too busy. 
o Recruitment limits: maximum number of participants were enrolled 
for the day so no further patients approached; for SF or LJ, RA was 
only recruiting for one of the two gestational age groups and the 


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participant was in the gestational age group that was not being 
recruited that day. 
o Other: please write in parentheses what the reason for not 
approaching the patient.  
 
• Approached: record the number of participants that you approached. Each 
patient approached should have a corresponding data Form 1. Verify at 
the end of each day that the number of Form 1’s completed matches the 
number “approached” recorded. 
 
• Declined: record the number of patients who declined to participate after 
you approached them about the study. For each participant that declines, 
ask the patient why they do not wish to participate. Record the reason(s) 
they provide for declining in the following column, separating each reason 
by a comma (ex: “don’t want extra injection, don’t want to spend extra time 
on study”). This response should also be documented on Form 1. 
 
• Determined ineligible after being approached: Based on their responses to 
Form 1 record the reason(s) the participant was found ineligible after 
being approached. These should also be recorded on Form 1. Ask the 
participant all of the eligibility questions regardless of eligibility status.  
 
• Enrolled: Record the number of participants enrolled for the day. Record 
the Enrollment ID of each participant enrolled under “Enrollment Numbers” 
column, separating each ID by a comma (SF001, SF002). 
 
• Randomized: Record the number of participants randomized for the day. If 
a participant was enrolled but not randomized (i.e. if # Enrolled ≠ # 
Randomized for the week) record the reason(s) for not being randomized, 
with each reason being separated by commas. The reason for not being 
randomized should also be recorded on Form 2. Reasons for not being 
randomized include ROM with dilator placement; patient withdrew from 
study before randomization; physician unable to complete injection; 
adverse event precludes patient completing study. 
 
Enrollment Log 
The enrollment log is used to track the progress of participants recruited for the 
study. In Column A, each row corresponds to a single participant.  
• Date: Record the date that the participant was enrolled (Day 1) 
 
• Enrollment ID: Record the participants Enrollment ID.  
 


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• Randomized?: Record whether the participant was randomized or not. If 
they were not randomized, record the reason(s), with each reason 
separated by a comma. The reason for not being randomized should also 
be recorded on Form 2. Reasons for not being randomized include ROM 
with dilator placement; patient withdrew from study before randomization; 
physician unable to complete injection. 
 
• Randomization ID: if the participant was randomized, record their 
Randomization ID 
 
• Discontinued from study: Record whether the participant discontinued 
from the study at any point prior to study completion after receiving an 
enrollment ID by writing “Yes” or “No”. If the participant did discontinue, 
record the reason for their discontinuation by writing the number 
corresponding to their reason, with each number separated by a comma. 
If the participant withdraws voluntarily from the study, ask the participant if 
the research team still has permission to access their medical chart and 
record their response.  
 
B. Protocol deviations log 
Protocol deviations are any deviation from the IRB-approved protocol that are not 
approved prospectively by the IRB. Major protocol deviations are deviations from 
the protocol that have the potential to negatively impact subject safety, the 
integrity of study data, or a subject’s willingness to participate in the study. Minor 
protocol deviations are deviations that do not have the potential to negatively 
impact subjects, their willingness to participate or data integrity. 
 
All protocol deviations must be reported to the coordinating center within 72 
hours of the site PI learning of the event. 
 
Protocol deviations must be recorded on the Protocol Deviations Logs as follows: 
• Record the Site ID (SF, LJ, LA, LB) in the designated s pace at the top of 
each page of the Protocol Deviations Log 
 
• Enrollment ID: Record the patient’s assigned Enrollment ID 
 
• Date the deviation discovered: Write the date that the deviation was 
discovered by study staff. Dates should be recorded as month/day/year 
(MM/DD/YYYY). 
 
• Date the deviation occurred: Write the date that the deviation actually 
occurred, even if it is not the same date as the day it was discovered. 
Dates should be recorded as month/day/year (MM/DD/YYYY). 


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• Description of deviation: Briefly describe what happened in the protocol 
deviation. 
 
C. Payment Log 
The Payment Log is meant to assist sites in documenting payment transactions 
with study participants. This log should be updated each time payment is given to 
a study participant. The Payment Log should be completed as follows: 
 
• Record the Site ID (SF, LJ, LA, LB) in the designated space at the top of 
each page of the Payment Log 
 
• Date: Write the date that payment is given to the study participant. Dates 
should be recorded as month/day/year (MM/DD/YYYY). 
 
• Study Day: Record the number of the study day on which payment was 
given. Day 1 is the day the patient was enrolled in the study. In most 
cases, $50 will be given on Study Day 1 and $50 will be given on Study 
Day 2.  
 
• Enrollment ID: Record the patient’s assigned Enrollment ID 
 
• Amount: Record the amount given to the patient that day 
 
• Study staff initials: The study staff who gave the money to the study 
participant should initial the Payment Log. 
 
Participants will receive their payment as cash or gift card. Cash will be kept in a 
locked safe box at each study site. 
 
D. Adverse events log 
Adverse events are any illness, pain or complication that occurred within the 
duration of the study. These may be expected (listed in Section VIII) or 
unexpected and may or may not related to the study participation. Each Adverse 
Event should be recorded on its own line even if it is related to another event 
(e.g. nausea & vomiting are two distinct AE’s and should be recorded 
individually). For each adverse event record: 
• Enrollment ID: Record the patient’s assigned Enrollment ID 
o If the same AE occurs for different patients (e.g. two patients both 
experience nausea) record this as two different AE’s. 
 


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• Randomization ID: Record the patient’s assigned Randomization ID if they 
were randomized 
• Event Description or Diagnosis: Record a brief description of the illness or 
complication. Whenever possible include a medical diagnosis if available. 
 
• Date Onset: Record the date the adverse event was first noticed 
 
• Date Resolved: Record the date the AE resolved. If the AE is ongoing, 
write “Ongoing” 
 
• SAE: Report whether the AE reported is considered a SAE (criteria for 
SAE’s covered in Section VIII) by checking “Yes” or “No”. If checked “Yes” 
follow SAE reporting protocol elaborated in Section VIII of this SOP. 
 
• AE Severity: Report the severity of the AE using the following numerical 
code: Mild=1, Moderate=2, Severe=3. Definitions for each are provided 
below: 
• AE Outcome: Record the outcome of the AE by writing “1” if the AE 
recovered/resolved, “2” if the AE is ongoing, “3” if the AE resulted in the 
death of the participant, and “4” if the AE outcome is unknown. 
 
• Relation to Study Drug: Record whether the study clinician believes that 
the AE is related to the study drug by recording “1” if the clinician believes 
the event to be unrelated, “2” if it is unlikely related, “3” if it is possibly 
related, “4” if it is probably related, or “5” if it is definitely related. 
 
• Treatment Needed: Record whether any treatment was required for the 
AE by writing “1” for no treatment, “2” for medication treatment and “3” for 
Non-drug treatment. Specify the medication or non-drug treatment on the 
lines provided on the AE log below the chart. 
 
E. Participant log 
Mild: Symptoms were annoying but did not get in the way of your usual 
activities. 
 
Moderate: Symptoms got in the way as you tried to do your usual activities but 
you were still able to do most of the things you needed to. 
 
Severe: Symptoms stopped you from being able to do your usual activities. 


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This is a master subject list specific to each site. This log is not sent to the 
coordinating center but rather remains in a locked cabinet or on a secure server 
at each study site. The log contains the Enrollment ID, Name and MRN. If the log 
is being kept electronically on a secure server, check “Electronic” on the top of 
the page and write the location/name of the file in the line provided. 
 
F. Monitoring log 
The Monitoring Log is a record of when site managers monitor the data at a 
particular site. These visits will occur as needed, with site managers traveling to 
the site to correlate completed forms with original copies and medical chart data 
at the site. Each site will have a Site Monitoring Log in their Study Binder, to be 
completed by the site manager from the coordinating center as follows.  
• Record Site ID: (SF, LJ, LA, LB) in the designated s pace at the top of 
each page of the Payment Log 
 
• Name of Monitor: Record the name of the site manager from the 
coordinating center completing the monitoring 
 
• Monitor Date: Record date of monitor. If monitoring occurred over multiple 
days, put range of dates (MM/DD/YYYY-MM/DD/YYYY). 
 
• Description: Record a brief description what was monitored on this 
occasion. 
 
The coordinating center will also have a Master Monitoring Log of all the 
monitoring that has occurred at any of the sites.  
 
G. Drug accountability log 
This is to be filled out by RA each time a drug is requested and drawn up. Keep 
track of the date, the randomization id number, and whether the drug was used 
or thrown away.  


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VII: INFORMATION EXCHANGE WITH THE COORDINATING CENTER 
 
A. Sending data collection forms 
 
Unless otherwise arranged, each site should send completed data collection 
forms to the coordinating center on a weekly basis every Friday. This includes 
Forms 1-5 for each study patient. Study staff should ensure that all forms are 
complete, accurate and legible. Original copies of all data collection forms 
(Forms 1-5) should be kept at the study site. These photocopies should be 
kept in a secure location for 5 years. 
 
In order to send the forms, please scan or fax the original copies of all data 
collection forms.  
- 
In order to scan the forms please email them to: Chiara.corbetta-
rastelli@ucsf.edu 
 
B. Queries 
 
The coordinating center will send data queries to the site study coordinators at 
each site as needed, with an average response time of 14 days following data 
collection forms being sent. These queries will be based on submitted data 
collection forms. Queries will be sent via email. Site study coordinators should 
ensure that queries are addressed appropriately and responses are sent to the 
coordinating center in a timely manner. Responses should be sent from the site 
to the coordinating center via email.  
 
C. Sending Logs to the Coordinating Center 
 
Study sites should send the following Logs to the coordinating center in the time 
frame indicated: 
- 
Adverse Events Log: Send a copy to the coordinating center on a weekly 
basis. This log can be scanned/emailed (chiara.corbetta-
rastelli@ucsf.edu). If no adverse events have occurred during that week, 
site study staff should email chiara.corbetta-rastelli@ucsf.edu to report 
that no adverse events occurred during the preceding week. 
 
D. Protocol Updates 
Protocol updates will be emailed to site investigators by the principal investigator 
or the site managers as they become available. A copy of each update should be 
printed and placed in the site’s Study Binder. The coordinating center will keep a 
Master Protocol Updates Log of every update that is issued. A copy of this log 
can be requested at any time by a site as well.  


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E. Delegation of Authority Log 
The Delegation of Authority Log provides a list of the various study tasks and 
responsibilities and the person(s) approved to complete these tasks. For each 
study responsibility, either an individual is listed by name or a category is 
described (RN’s, midwives, residents, etc). Only someone listed by name or 
falling into a listed category can perform the study responsibility. 
 


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VIII. SERIOUS ADVERSE EVENTS 
 
An adverse event is any unfavorable medical occurrence in a study participant, 
including any abnormal sign, symptom or disease that is temporally associated 
with the subject’s participation in the research, whether or not it is considered 
related to the subject’s participation in the research. 
 
A serious adverse event (SAE) is an event that: 
Is life threatening 
Requires inpatient hospitalization or prolongation of existing 
hospitalization 
Results in a permanent or serious disability 
Results in a congenital abnormality 
Results in death 
Important medical events that may not result in death, be immediately life-
threatening, or require hospitalization may be considered an SAE when, based 
upon appropriate medical judgment, they may jeopardize the subject and may 
require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. Examples of such events are intensive treatment in an Emergency 
Room or at home for allergic bronchospasm; blood dyscrasias, or convulsions 
that do not result in hospitalization; or development of drug dependency or drug 
abuse. 
 
Reporting SAEs 
 
All SAEs, whether or not there is a probable relationship with the study drug or 
with the study procedures, must be reported by the site investigator to their 
coordinating center site manager within 24hrs of his/her becoming aware of the 
SAE. Coordinating center staff will report SAEs promptly to NEIRB and the 
IDMC. Sites using their own IRB must additionally report the SAE to their IRB 
(FPAWH in Long Beach and Los Angeles should report any SAE’s to the 
Coordinating center. Lovejoy clinic should report any SAE’s to both the 
Coordinating Center and their own IRB). Site investigators must also report all 
SAEs occurring up to two weeks after the participant is discharged from the study 
IF the event is thought to be related or possibly/probably related to the study. 
 
Reporting of a SAE can be done by phone or email. When reporting a SAE to the 
coordinating center, the site investigator should refer to the subject by her 
Enrollment ID to protect patient privacy. Sites will work with the coordinating 
center to complete the Serious Adverse Event Reporting Form after this initial 
contact is made to report the SAE.  
 


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Principal investigator: Jennifer Kerns, MD, MPH. Jennifer.Kerns@UCSF.edu  
510-502-4340 
Research manager: 
 
 
 
Chiara Corbetta-Rastelli 
Chiara.Corbetta-Rastelli@UCSF.edu 
Cell: (314) 387-3575 
 
 
Assessing AEs 
 
Monitoring for and documentation of adverse events related to the cervical 
dilation, medication injection and/or D&E of study participants, whether 
anticipated or unanticipated, is the responsibility of the site investigator, who will 
maintain oversight of the site’s adverse events, but she may delegate collection 
of information related to this function to the site’s research coordinator.  
 
 
Possible adverse events related to the medication injection include those below. 
- 
Injection site pain or bruising 
- 
Nausea and vomiting 
o Only report in AE log if patient reports severe nausea or vomiting, 
patient treated with more than one anti-emetic agent (ex. Zofran 
and Compazine), or patient treated with multiple doses of anti-
emetic agent (ex. Patient given 3 doses of Zofran for nausea). 
- 
Out of hospital delivery 
- 
Bradycardia 
- 
Endometritis, sepsis 
 
Possible adverse events related to the D&E include those below. None of the 
risks listed below would be solely due to the study procedures but are rather 
potential adverse events that may be related to standard D&E or 
anesthesia/analgesia/uterotonic agents that accompany the D&E. 
 
- 
Hemorrhage 
o Requiring intrauterine tamponade (with Foley, Bakri, packing) 
o Requiring transfusion 
o Requiring embolization 
- 
Uterine re-evacuation (for retained tissue, hematometra, bleeding) 
- 
Endometritis, sepsis 
- 
Cervical laceration requiring stitches 
- 
Uterine perforation 
- 
Abdominal surgery (laparoscopy, laparotomy, hysterectomy) 


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- 
Transfer to the hospital for any indication (even if the subject is not 
admitted) 
- 
Allergic reaction/hypersensitivity/anaphylactic shock 
- 
Vasovagal episode 
- 
Syncope 
- 
Anesthesia complications 
- 
Cardiopulmonary arrest 
 
These adverse events should be documented on Form #2 if they occur on Day 1 
and Form #4 if they occur on Day 2 for acute events and Form #5 for delayed 
events and on the Adverse Event Log. The Adverse Event Log will include an 
assessment of whether the adverse event is unrelated, possibly/probably related, 
or related to the study medications. A copy of the Adverse Event Log should be 
sent from each site to the coordinating on a weekly basis. Any adverse events 
that is unexpected (not on list above) and related or possibly/probably related 
must be reported to the coordinating center within 5 working days or 7 calendar 
days of the date the site investigator first becomes aware of them. The principal 
investigator will review these adverse events at bi-weekly research meetings at 
the coordinating center. 


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IX. Detailed Data Analysis Plan 
 
Efficacy endpoints 
Primary endpoint: comparison of D&E operative time between two study arms 
(digoxin injection vs placebo injection) 
Secondary endpoints: comparison of ease of procedure, achievement of fetal 
demise, and procedure complications between two study arms (digoxin injection 
vs placebo injection). 
 
Safety endpoints 
The Data and Safety Monitoring Board will provide recommendations about 
starting, continuing and stopping the study. Safety evaluations will monitor for 
statistically significant higher complication rates than complication rates for clinic 
in procedures of same gestational duration and for adverse events. The DSMB 
will meet to determine criteria for interim analysis and for stopping the trial. 
 
Statistical analysis 
For primary outcome analysis, we will use an intention-to-treat analysis and 
compare median procedure time using a paired t test. To control for site, we will 
conduct a regression with site as the single factor. In the event that any potential 
confounders are not balanced by randomization, we will control for those in the 
analysis. Controlling for site will not necessitate an increase in our sample size. 
We will do descriptive analyses of secondary outcomes using chi-square 
and t tests where appropriate.  
 
Sample size 
Sample size was calculated for the primary outcome of procedure time. In order 
to detect at least a 3-minute difference in procedure time between groups with 
80% power and alpha of 0.05 (using a 2-way test), we would need 172 patients, 
or 86 per arm. Loss to follow up only would occur if a subject was randomized, 
received the injection and dilators, then failed to return for her procedure. In order 
to account for this rare but possible situation, we intend to enroll a total sample of 
N=180 subjects.