Clinical trial NCT02083809
Conditions: Abortion Dilation and Evacuation Hemorrhage Blood Loss
Sponsor: University of Hawaii
Start date: 2014-10-01; Completion date: 2018-02-01
Enrollment: 166 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Currently, there is very little research to identify ways to decrease blood loss during D\&E (dilation and evacuation) procedures. The objective is to determine whether routine use of intravenous oxytocin will improve bleeding outcomes at the time of D\&E at 18-24-weeks gestation. To evaluate the hypothesis, investigators will perform a randomized, double-blinded, placebo-controlled trial. The patient will be followed until discharged from the postoperative care unit during which time patient satisfaction, pain score and postoperative bleeding will be assessed.

Detailed description:

Arms: arm 1: 500ml saline or lactated ringer without oxytocin added arm 2: Intravenous oxytocin mixed with saline or lactated ringer
Interventions: intervention 1: intravenous oxytocin intervention 2: Intravenous Fluids and Electrolytes
Intervention descriptions: intervention 1: 30 units of oxytocin added to 500ml of inert IV fluid (saline, lactated ringer) intervention 2: 500 ml of inert IV fluid

Protocol documents:
Prot_SAP_000.pdf: 
 
 
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A randomized double-blinded controlled trial comparing dilation and evacuation outcomes 
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with and without oxytocin use 
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NCT02083809 
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26 August 2014 
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List of Abbreviations 
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ACOG = American Congress of Obstetricians & Gynecologists 
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AE = adverse event 
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BMI = body-mass index 
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D&E = dilation and evacuation 
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DIC = disseminated intravascular coagulation  
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DSMP = data safety monitoring plan  
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DSMB = data safety monitoring board 
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EBL = estimated blood loss 
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NAF = National Abortion Federation 
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IUD = intrauterine device 
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IV = Intravenous 
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LMP = last menstrual period 
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QMC = Queens Medical Center 
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SAE = serious adverse events 
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UH = University of Hawaii 
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UW = University of Washington 
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VAS = visual analog scale 
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WIRB = Western Institutional Review Board  
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Project Summary/Abstract 
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Study Title:  A randomized double-blinded controlled trial comparing dilation and evacuation 
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outcomes with and without oxytocin use 
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Objective:  Our study objective is to determine whether routine use of intravenous (IV) oxytocin 
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will affect bleeding outcomes at the time of dilation and evacuation (D&E) at 18 to 24-weeks 
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gestation.   
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Background:  Abortion is one of the most common procedures performed in the United States.  
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While surgical abortion is considered to be a safe procedure, rates of hemorrhage, the most 
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common complication that occurs at the time of surgical abortion, increase with gestational 
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age.  Few studies have identified effective interventions to manage blood loss during D&E 
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(dilation and evacuation), the procedure used to terminate pregnancy above 14 weeks 
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gestation.  Many practitioners use uterotonics, including oxytocin, to help minimize blood loss, 
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however, oxytocin administration has never been studied with D&E.   
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Design: We propose a randomized, double-blinded, placebo-controlled trial at two sites, the 
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University of Hawaii (UH) and the University of Washington (UW).  Subjects who present for 
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D&E at 18 to 24-weeks gestation will be recruited and randomized to IV oxytocin versus IV fluid 
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alone.  Bleeding will be measured during the procedure and until the time of discharge from the 
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postoperative care unit.   
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Outcomes:  The primary outcome is the rate at which providers intervene to control blood loss 
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during D&E procedures.  Interventions include bimanual massage, administration of 
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medications (i.e. misoprostol, methergine) and performing additional procedures (i.e. 
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placement of an intrauterine tamponade balloon, exploratory laparoscopy or laparotomy).  
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Secondary outcomes include measured blood loss, complication rates, procedure length, and 
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postoperative pain and satisfaction.   
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Sample size & population:  We designated a 15% decrease in provider interventions to control 
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blood loss to be clinically significant.  To achieve this, with 80% power and two-sided alpha of 
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0.05, we need 83 subjects per group for a total sample of 166 women.  Patients will be 
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recruited in Honolulu, HI at the UH site and Seattle, WA at the UW site.  Eligible participants 
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include women 14-years and above presenting for termination of pregnancy including those 
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with fetal demise or fetal anomalies.   Exclusion criteria include placenta accreta, preoperative 
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misoprostol use, or women unable or unwilling to provide written informed consent. 
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1.  Background & Rationale 
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Nearly 1.2 million abortions are done in the United States each year, making it one of the most 
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common surgical procedures performed (1).  Only a small number of surgical abortions, 1.9 per 
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1000 procedures, result in a complication (1, 2).  Dilation and evacuation (D&E), the surgical 
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procedure used to terminate pregnancy above 14 weeks gestation, has a higher risk of 
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complication.  Hemorrhage, defined as blood loss over 500-ml, occurs in 0.8% to 2.1% of all 
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D&E procedures and is the most common complication of D&E (3, 4).  The rate of hemorrhage 
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increases with gestational age; up to 6.3% of D&Es performed above 18 weeks gestation are 
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affected by hemorrhage (5).  
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In an attempt to decrease hemorrhage with D&Es, many abortion providers routinely 
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administer uterotonics like oxytocin (6).  The ability of oxytocin to decrease bleeding is 
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extrapolated from the obstetric literature where clear evidence demonstrates that it decreases 
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hemorrhage when used routinely at the time of a full-term delivery.  Studies evaluating routine 
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oxytocin for first-trimester surgical abortion failed to show any change in blood loss (7, 8).  To 
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date, no randomized trials have evaluated routine oxytocin administration at the time of D&E in 
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the second trimester.  Because of its effect on blood loss at the time of a term delivery, 
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oxytocin is often used during surgical termination of pregnancy at a variety of gestational ages.  
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There is no documented “standard of care” in the literature regarding prophylactic use of any 
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uterotonics during D&E.   At The Queen’s Medical Center (QMC), many providers very 
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commonly use oxytocin at the time of D&E.  We seek to determine whether this intervention 
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decreases blood loss and the need to perform interventions to control bleeding.   
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We have performed a preliminary retrospective analysis of a subset of patients (n=23) 
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undergoing D&E at 18- to 24-weeks (Study Title: Abortion Database, WIRB Approved, Study ID 
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2013-88).  This study included procedures performed by UH/UCERA Faculty Physicians.  Eight of 
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23 (34.8%) patients included in this subset received oxytocin.  We found that those who 
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received oxytocin had a mean estimated blood loss (EBL) of 112.5-ml while those who did not 
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receive oxytocin had a mean EBL of 135.3-ml.  A difference in blood loss of 22.8-ml (about 5 
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teaspoons) does not have any clinical consequences for the patient.  In other words, the patient 
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does not experience a drop in their blood count (hemoglobin), would not have any symptoms 
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of anemia (lightheadedness or weakness), and would not require any additional treatment 
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because an additional 22.8-ml of blood was lost during a procedure.  
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Importantly, this retrospective analysis does not properly answer our clinical question.  For a 
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research study to answer a question it is important to be able to properly assess the following: 
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1. Exposure – In this case the exposure is whether or not the patient received oxytocin 
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and the dose of oxytocin.  With a retrospective analysis, we are “stuck” with 
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whatever information is available in the medical record.  In terms of collecting 
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information on the exposure (oxytocin), we have information on whether a patient 
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received oxytocin but the amount infused was not always recorded.   
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2. Outcome – In this case, the outcome is estimated blood loss.  In terms of collecting 
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information on the outcome, estimated blood loss recorded in the medical record, is 
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known to be unreliable, inconsistent, and not uniformly collected.  Typically in the 
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operating room, the surgeon and anesthesiologist estimate blood loss by visually 
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inspecting the amount of blood in the collection canister and the blood on surgical 
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sponges.  It is no surprise that one obstetrical study comparing estimated and 
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measured blood loss demonstrated a difference of nearly 300-ml between the two 
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groups (9, 10).   
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3. Confounders – A confounder is something that “mixes” or “blurs” the effect.  A 
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researcher may be attempting to relate an exposure to an outcome but is actually 
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measuring the effect of a third factor, known as a confounding variable to the 
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outcome.  For example, the results of our preliminary analysis show that patients 
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who did not receive oxytocin had slightly less bleeding.  However, what if some 
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confounding factor (i.e. low platelets, higher gestational age, multiple gestation, 
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etc.) made it more likely for patients who had a higher risk of bleeding to get 
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oxytocin?  Although we were trying to measure the effect of oxytocin on bleeding 
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we may have in fact been measuring the hidden effect of confounders on bleeding.  
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Sometimes confounders are easily identifiable, sometimes they are unknown, yet-
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to-be identified factors.    
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The retrospective analysis we conducted does not adequately address our scientific question 
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because of the three factors listed above.  In our randomized controlled trial we will be able to 
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improve on the quality of data collected in the following ways; 
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1. Exposure – We will know if a patient received oxytocin and those who get oxytocin 
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will get a standard amount of the medication 
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2. Outcome – Blood loss will be accurately measured rather than estimated.   
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3. Confounders - Conducting a randomized controlled trial is the best way to avoid 
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confounding because assignment of participants into one group or another happens 
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purely by chance.  In other words, possible confounders don’t affect whether the 
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patient receives or does not receive the intervention. 
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Though oxytocin is a safe, inexpensive medication, no medication is administered without some 
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risk.   Some abortion providers hypothesize that use of oxytocin can make it more difficult to 
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remove pregnancy tissue because the uterine muscle contracts around the surgical instrument 
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making them difficult to manipulate (5).  Oxytocin may increase postoperative uterine cramping 
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causing the patient unnecessary discomfort (11).  Though no published reports describe adverse 
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events when oxytocin is used at the time of D&E, when used during labor and delivery at term 
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or induction termination in the second and third trimester, oxytocin related complications such 
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as anaphylaxis, uterine rupture, arrhythmias and water intoxication have been reported (12-
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15). Unnecessary use of oxytocin would raise abortion related healthcare costs both directly, 
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via the cost of the medication, and indirectly, via the cost of treating related adverse events and 
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pain. 
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This study will be conducted in compliance with the protocol approved by the Research and 
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Institutional Review Committee, and according to Good Clinical Practice standards, applicable 
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federal regulations, and QMC institutional policies, and QMC research policies and procedures.   
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2.  Specific Aims/Objective/Purpose: 
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Primary Objective:  Our primary objective is to determine whether routine use of oxytocin 
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decreases the rate of intervention to decrease excess blood loss compared to IV fluid alone in 
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women having D&E between 18- and 24 -weeks gestations (for special considerations for 22- to 
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23-week and 6-day gestations see Inclusion Criteria).   Interventions to decrease bleeding have 
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been defined as bimanual massage, use of uterotonics (misoprostol, methylergonovine, 
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carboprost tromethamine), injection of additional vasopressin, balloon tamponade or packing, 
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re-aspiration, exploratory laparotomy or laparoscopy, need for uterine artery embolization or 
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hysterectomy. 
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Secondary Objectives:   
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• Measured blood loss (described in section 6 under “Surgical Protocol”) 
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• Procedure length, measured from placement of the speculum to removal of speculum  
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• Complications including uterine perforation, cervical or vaginal laceration, hemorrhage 
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(blood loss greater than 500 ml), need for transfusion, exploratory laparotomy or 
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laparoscopy  
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• Postoperative pain: recorded 60-minutes after the end of the procedure using a 10-cm 
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visual analog scale (VAS) and compared to preoperative baseline score 
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• Patient Satisfaction: measured 60-minutes after the procedure using 5-point scale and 
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compared to preoperative baseline score 
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3.  Study Design 
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Overall Study Design 
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We propose a randomized, double-blind, placebo-controlled trial of women undergoing D&E at 
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18- to 24-weeks gestation (for special considerations for 22- to 23-week and 6-day gestations 
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see Inclusion Criteria).  Women will be randomized to receive 30-units of IV oxytocin versus IV 
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fluid alone.  This study will be performed at two sites: The Queen’s Medical Center (UH site, 
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Honolulu, Hawaii) and University of Washington Hospital and Clinics and Cedar River Clinic (UW 
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sites, Seattle, WA).  The gestational-age limits were selected for two reasons.  First, studies 
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have shown rates of hemorrhage increase significantly past 18-weeks gestation and are 
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reported to be as high as 6.3% (5).  Second, a survey of abortion providers who participate in 
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the Family Planning Fellowship LISTSERV found that providers who routinely use oxytocin 
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during D&E generally do so starting at 18-weeks gestation. 
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Description of the drug to be studied 
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Pitocin®, or synthetic oxytocin, is made by JHP Pharmaceuticals in Rochester, MI.  The research 
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pharmacists at each site will be given a randomization scheme and will accordingly prepare an 
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IV solution that contains either 500-ml of lactated ringers or 500-ml of fluid mixed with 30-units 
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of oxytocin. Study medications will be labeled with study identification numbers based on 
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allocation (see Randomization).   
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Sample Size & Duration 
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We designated a 15% decrease in intervention rates to control blood loss as clinically 
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significant.  To achieve this, with 80% power and two-sided alpha of 0.05, we need 83 subjects 
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per group for a total sample of 166 women.   At the UH site (QMC), we estimate 100 D&E 
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procedures between 18- and 24-weeks gestation will be performed over the next 12-months.  
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We estimate 50% of all eligible patients will agree to participate giving us an enrollment of 
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approximately 55-60 patients over a 14-month period.  UW site investigators have estimated 
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180 abortions at 18- to 24-weeks will occur over the next year.  Similar to the UH-site, we 
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estimate 50% of eligible subjects will be recruited and we should therefore enroll about 100-
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120 patients in 14-month period.  Each subject’s involvement lasts from the time of the pre-
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operative visit until discharge from post-operative unit.   
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Randomization 
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An individual not involved with subject recruitment, enrollment or follow-up will determine 
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allocation of subjects by computer-generated random numbers in block sizes to be determined 
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by that individual.  The investigators will provide research pharmacists sealed, sequentially-
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numbered, opaque envelopes containing study group assignment which will be decided on the 
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day of surgery.  The research pharmacists will prepare study medication (either IV fluid alone or 
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IV fluid with oxytocin) and will label the fluid bag with a study identification number.  
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Investigators will assign each subject a study identification number in sequential order.  Study 
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medication will be delivered to the operating room prior to the procedure. 
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The research pharmacist will be the only individual not blinded to group assignment and will 
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not have contact with study investigators or the research coordinators prior to the procedure.  
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An opaque sealed envelope outlining group assignment (oxytocin or IV fluid alone) will 
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accompany each solution of IV fluid.  The research assistant will keep this envelope with them 
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during the procedure.  The surgeon, anesthesiologist and all assistants will be blinded to group 
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assignment.  However, the surgeon or anesthesiologist may instruct the research assistant to 
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open the envelope to determine group assignment if the patient exhibits signs of complications 
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directly related to oxytocin such as anaphylaxis, arrhythmia, or water intoxication or in case of 
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emergency where the physician feels unblinding is necessary. 
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Follow-up procedure  
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Study procedures will end when the patient is discharged from the medical facility.  Patients 
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will receive standard post-abortion care as performed at the various practice sites.  In terms of 
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post-operative pain and satisfaction assessment, this will be assessed approximately 1-hour 
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after the D&E in the recovery room.  Any complications that occur before the patient is 
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discharged from the medical facility will be recorded.  
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Study Flow Schematic 
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4.  Eligibility Criteria 
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A.  Inclusion Criteria: 
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• Age greater than or equal to 14-years 
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• Requesting pregnancy termination 
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• Intrauterine pregnancy at 18- to 23 weeks and 6 days gestation  
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o Gestational-age to be confirmed by ultrasound (See section 6) 
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o We will perform procedures in full compliance with QMC Abortion Policies.  At 
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QMC, intentional termination is performed at 18- to 21-weeks and 6-days 
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gestation but may be performed up to 23-weeks and 6-days gestation in the 
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following circumstances: 
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§ Fetal anomaly  
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§ Intrauterine fetal demise  
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§ Victims of rape or incest 
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§ Woman’s life is in danger 
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• Subjects must be willing and capable of giving informed consent and able to understand 
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and sign written consents in English. 
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B.  Exclusion Criteria: 
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• Ultrasound findings suggestive of placenta accreta 
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• Patients requiring preoperative misoprostol 
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In clinical research, pregnant patients are considered to be a vulnerable research population 
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due to the interplay of maternal and fetal health risks.  In the case of patients seeking abortion, 
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the focus is turned solely to the health of the woman as the pregnancy is undesired and will be 
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terminated.   
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Minors are also considered a vulnerable research population and we will seek IRB approval to 
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include patients aged 14-years and older.  In both Hawaii and Washington State, parental 
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consent is not required for minors age 14-years and older to receive pregnancy care, including 
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an abortion.  According to the American College of Obstetricians and Gynecologists (ACOG) 
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Committee Opinion on “Guidelines for Adolescent Health Research”, the Code of Federal 
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Regulations allows parental consent to be waived in clinical situations where parental 
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permission is not typically required.  The Code of Federal Regulations also states that, “in 
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certain research studies, adolescent minors would not be considered children and parental 
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permission would not be required.  Such research includes certain clinical studies involving 
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pregnancy, family planning, and treatment of STDs where the adolescent can legally consent to 
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such services.” (16) There is no published medical evidence or theoretical reason why 
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adolescents would have a higher risk of complications during D&E than adults. 
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Through our consent process, we will make it clear that participation in this study is voluntary.  
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Participants will not be approached until after they have already secured medical care for the 
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abortion procedure (i.e. preoperative evaluation, consent for the abortion procedure, and 
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scheduling are complete).  We will not post advertisements for recruitment and will only 
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approach patients who have already consented to the abortion procedure.  Subjects will not be 
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provided with any remuneration for study participation.  We will make it clear that if patients 
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are not willing to participate in the study, they will still be provided the same standard of care.   
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5.  Recruitment/Enrollment 
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Study Population 
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The study population will consist of female patients aged 14 and older who request D&E at 18- 
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to 24-weeks gestation (for special considerations for 22- to 23-week and 6-day gestations see 
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Inclusion Criteria).  This study will be conducted at UH (QMC) and UW. 
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Subject recruitment, admission and allocation 
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Providers (listed in Appendix C – Roles of Personnel) will approach patients who meet inclusion 
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criteria about study participation at the preoperative visit, which takes place in UH Faculty 
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Practice Sites at least one- to two-days before the procedure.  Invitation to participate will be 
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offered only after patients have received standard counseling and have provided written 
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consent for the abortion procedure itself.  It will be made clear to all patients that their decision 
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to enroll or not enroll in the study will not affect their access to requested abortion care.  
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Consent for the study will be obtained by study investigators.  In the rare instance that the 
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investigators recruit another physician’s patient, attending physician permission will be 
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obtained first, before approaching the patient.  After enrollment, a copy of the study consent 
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will be given to the subject (see Consent Form attachment). 
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No advertisements will be posted for this study.  Subjects will be recruited at UH Faculty 
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Practice sites (i.e. not part of QMC).  At the UW site, subjects will be recruited at Cedar River 
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Clinic or UW Hospital and Clinics where they will also perform the procedures in the outpatient 
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setting.  On the day of the procedure, the surgeon will meet with the subjects one- to two-
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hours before the procedure to confirm they are still willing to participate.   
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Criteria for Discontinuation  
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Participants may end study participation upon request at any point in the study.  For example, 
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they may withdraw any time prior to the procedure or they may decline to complete 
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postoperative the postoperative satisfaction and pain score.  After study consent and 
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randomization but prior to the procedure, patients may be discontinued if it is revealed that the 
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patient meets any of the exclusion criteria.  
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We will follow intention-to-treat principles and analyze all data based on its allocation 
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regardless of whether or not the intervention was received.  
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6.  Study Procedures/Protocol 
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Procedure setting 
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At UH faculty practice sites, surgical abortions above 18-weeks gestation are performed in an 
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operating room setting.  One of six experienced D&E providers will perform all procedures.   At 
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the UW site, one of two experienced D&E providers will perform all abortions in either the 
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operating room or outpatient surgical center setting.  At both sites, fellows may participate in 
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the procedure under direct supervision.  In study documents, we will record the name of the 
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surgeon, whether a fellow participated in the procedure and their level of training. 
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Screening/Preoperative evaluation 
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Patients requesting abortion procedures who meet inclusion criteria will be recruited at the 
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preoperative visit which typically occurs one- to two-days before the procedure at the UH 
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faculty practice sites, however, if patients have any doubts or ambiguity about the abortion, 
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they can be given as much time as they need to consider their options before scheduling 
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surgery.  Study investigators will thoroughly consent patients for the study (see Subject 
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Recruitment, Admission, Allocation).   
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Standard pre-operative counseling and assessment (including routine blood or laboratory tests) 
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will be done, contraceptive counseling will be performed and surgical consent will be obtained.  
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For patients with HMSA insurance, we have received pre-approval status.  Therefore, no 
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additional actions need to be taken on the part of the subject or investigators to assure health 
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insurance coverage.  The preoperative care of study participants will differ from usual care in 
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the following way: 
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• Components of demographic and health related information will be recorded in study 
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documents.  All information recorded in study documents is part of usual preoperative 
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assessment.  We will not be obtaining any additional information from study 
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participants 
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Pre-operative evaluation on the day of surgery 
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In the pre-operative area, the following study procedures will be performed: 
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• Approximately one- to two-hours before the procedure, providers will confirm that 
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subjects are willing to participate.   
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• Pain/Satisfaction Assessment:  The research assistant will assess subject’s pain score 
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using a 10-cm VAS and patient satisfaction using a 5-point scoring system within 60-
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minutes of the procedure.  Assessment will be made before any anesthetic medications 
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have been given.  These values will serve as a baseline to compare with the 
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postoperative assessment described later.   
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Intraoperative Evaluation 
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Participation in this study does not alter the key portions of the surgical procedure.  Standard 
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D&E procedures will be performed under ultrasound guidance according to the usual standard 
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of care.  Each patient will receive general anesthesia or deep sedation with choice and dosage 
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amounts of anesthetic agents decided by the anesthesiologist.  Unless there is a 
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contraindication, surgeons will give all patients 5-units of vasopressin mixed with 10-mL of 
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saline in a paracervical block.  This is the current practice at QMC based on scientific evidence 
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(17) and recommendations by the National Abortion Federation (NAF) (18) and Society of 
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Family Planning (SFP) (3).  As is the usual practice, amniotic fluid is drained from the uterus 
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prior to removing products of conception.  Intraoperative care of study participants will differ 
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from usual care in the following ways:   
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• Study Drug Administration:  Upon speculum insertion, 500-ml of lactated ringers or 500-
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ml of lactated ringers with 30-units of oxytocin will be given as an IV fluid bolus infusion 
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over approximately 15-minutes.  The dose of oxytocin is extrapolated from the obstetric 
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literature; oxytocin is used at this does at the time of term delivery at QMC and 
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throughout the US (16).  Currently, the same dose of oxytocin is very commonly 
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administered at QMC on labor & delivery and during D&Es.   
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• Blood Loss Measurement:  It is the usual practice at QMC for the surgeon to handle all 
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products of conception throughout the procedure until it is sealed in a specimen 
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container and they will continue to do so.  Simple visual inspection is known to be 
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inaccurate in estimating blood loss (9, 10).  Thus, following the procedure, the surgeon 
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or research assistant will measure blood loss with a graduated cylinder.   
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• Weighing of gauze and sponges: Used gauze or sponges will be weighed and the dry 
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weight of the gauze or sponge will be subtracted and converted from grams to milliliters 
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using a one-to-one ratio. 
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• Measurement of procedure length:  The research coordinator will measure and record 
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length of procedure in seconds starting from when the speculum is placed and ending 
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when the speculum is removed from the vagina.   
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In rare cases, the surgeon may not able to separate amniotic fluid from blood.  In these cases, 
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hematocrit of the blood-amniotic fluid mixture will be checked at completion.  This hematocrit 
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will be compared to the patient’s preoperative serum hematocrit to determine the dilution 
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ratio and ascertain blood loss.  We plan to validate this process by performing the same 
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hematocrit assessment on a subset of patients whose amniotic fluid was separated at the start.   
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Intraoperative complications such as hemorrhage (blood loss greater than 500-ml), need for 
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transfusion, uterine perforation, cervical laceration, vaginal laceration, or need for laparoscopy 
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or laparotomy will be documented.  Complications such as cervical or vaginal laceration, or 
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uterine perforation, will be managed according to current standards of care.  The research 
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coordinator will record all such events in the study documents.  If the surgeon is concerned for 
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excessive bleeding due to uterine atony, measures will be taken to manage it.  The decision to 
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intervene will be based on signs of impending hemorrhage such as the presence of brisk and/or 
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prolonged, bright red, vaginal bleeding or accumulation of over 200ml of blood loss with 
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ongoing significant bleeding or signs of hemodynamic instability.  Ultimately, the provider 
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involved must use their best clinical judgment to decide when to intervene.  When providers 
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feel it is necessary to intervene, they will perform the following interventions in the order 
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described below (3): 
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1. Bimanual uterine massage 
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2. Intramuscular methylergonovine 0.2-milligrams (may repeat dose in 2- to 4-hours) 
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3. Rectal misoprostol 800-micrograms  
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4. 250-micrograms of intramuscular carboprost tromethamine (may repeat dose every 
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15- to 90-minutes) 
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5. Intra-uterine balloon tamponade  
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13
6. Additional surgical procedures such as re-aspiration after procedure completion, 
420 
exploratory laparotomy or laparoscopy (including those resulting in hysterectomy), 
421 
or uterine artery embolization. 
422 
 
423 
The rationale for using an algorithm is to standardize the care of patients and more accurately 
424 
assess our main study outcome, the need for intervention to control bleeding.  Study 
425 
investigators agreed upon the order of interventions because it so closely mirrors current 
426 
clinical practice, though a written algorithm does not currently exist.  The algorithm does not 
427 
dictate that a provider must wait a certain amount of time between steps.  If the provider feels 
428 
they need to move on to the subsequent step in the algorithm to best care for the patient, they 
429 
may do so at any time.  If contraindications to one of the uterotonics exist, the provider may 
430 
skip to the next step in the algorithm and this will be documented.   Providers may use 
431 
additional injections of vasopressin at any time during the procedure at their discretion to 
432 
control excess bleeding; these additional injections will be noted in the study documents.   
433 
 
434 
Postoperative Evaluation 
435 
After the procedure is complete, the surgical team will transfer the patient to the recovery unit 
436 
where she will spend a minimum of 60-minutes (6).  The following will be performed in the 
437 
postoperative care unit: 
438 
• Pain management:  All patients will receive 15-milligrams of IV ketorolac or 500-
439 
milligrams of oral naproxen at the time of procedure completion unless they have 
440 
contraindications to these medications (18, 19).  Anesthesiologists may give alternative 
441 
or additional doses of pain medication if the patient does not obtain relief with initial 
442 
dose.  All pain medications administered will be recorded in study documents.    
443 
• Pain/Satisfaction Assessment:  The research assistant will assess patient satisfaction and 
444 
postoperative pain 60-minutes after the procedure.  Satisfaction will be assessed using a 
445 
5-point scoring system and pain will be assessed using a 10-cm VAS (19-21).   
446 
• Postoperative Bleeding Assessment:  Before the patient is discharged, the research 
447 
assistant will collect and weigh all used pads to quantify postoperative bleeding, 
448 
subtracting out the weight of a dry pad from the used pad.   
449 
• Monitoring for Signs of Adverse Events:  Respiratory rate, heart rate and oxygen 
450 
saturation will be continuously monitored from the time oxytocin is administered until 
451 
subject arrives in the post-operative area as is the usual routine for patients having 
452 
surgery.  Blood pressure will be measured at frequent intervals as determined by the 
453 
anesthesiologist.  When patients are in the postoperative recovery area, vital signs will 
454 
be checked per the QMC Same Day Surgery protocol which includes continuous heart 
455 
rate and oxygen saturation with blood pressure checked every five-minutes for the first 
456 
15-minutes, every 15-minutes for the next hour, then every hour.  Patients will be asked 
457 
every 30-minutes if they are experiencing symptoms of pain, bleeding, heart 
458 
palpitations.  Any complications that occur postoperatively will be recorded.  
459 
 
460 
Please see attached Data Collection forms, which will be used throughout the above processes.  
461 
See Study Flow Schematic for visual representation of the above. 
462 
 
463 


 
 
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14
7.  Drug Supply, Packaging, Labeling and Storage 
464 
Pitocin ® or synthetic oxytocin is made by JHP Pharmaceuticals in Rochester, Michigan.  It is 
465 
currently stocked by the pharmacy and a supply of study medication may be ordered by the 
466 
QMC pharmacy.  Oxytocin is supplied as packages of twenty-five oversized 1-mL vials, each 
467 
containing 10 units of oxytocin or as a 10-mL multiple-dose vial containing 10 units of oxytocin 
468 
per mL (total = 100 units of oxytocin).  It must be stored at 15°–25°C (59°–77°F).  With proper 
469 
storage, the shelf life of this medication is up to 3-years.  Once mixed in a bag of IV fluids, the 
470 
solution expires after 90-days.  The manufacturer provides standard labeling of oxytocin vials; 
471 
however, study drugs will be re-labeled by the research pharmacist to conceal the 
472 
randomization status of the subject. All listed providers have prescribing privileges for study 
473 
medications.  
474 
 
475 
8.  Statistical Methods 
476 
Patients may discontinue from the study at any time.  If a patient withdraws, we will follow 
477 
intention-to-treat principles and will analyze subjects in the groups they were assigned to.   
478 
 
479 
Primary Outcome:  Use of any of the following interventions to control bleeding: 
480 
• Bimanual massage 
481 
• Uterotonics including: misoprostol, carboprost tromethamine, methylergonovine 
482 
• Injection of additional vasopressin 
483 
• Balloon tamponade 
484 
• Re-aspiration after procedure completion 
485 
• Exploratory laparotomy or laparoscopy  
486 
• Uterine artery embolization 
487 
• Hysterectomy 
488 
 
489 
We will compare intervention rates between treatment and control groups using a chi-square 
490 
test.  If significant differences in demographic or abortion related characteristics exist between 
491 
study groups, we will employ multiple logistic regressions to control for these differences.   
492 
 
493 
Secondary Outcomes: 
494 
• Measured blood will be compared using a student’s t-test.  
495 
• Procedure length will be compared using a student’s t-test 
496 
• Complications (described in Section 6) will be compared using a chi-square test 
497 
• Postoperative pain will be compared using a student’s t-test 
498 
• Patient Satisfaction will be compared using a student’s t-test 
499 
 
500 
We anticipate that some outcomes such as measured blood loss and procedure length may not 
501 
be normally distributed.  If this is the case, we will use an appropriate transformation to 
502 
normalize the data distribution prior to analysis.   
503 
 
504 


 
 
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15
No interim analysis is planned.  A Data Safety Monitoring Board (DSMB) has been assembled to 
505 
review data (See Section 10B, Page 20).  Otherwise, the principal investigators will be 
506 
responsible for protecting and monitoring the rights, safety and welfare of the subjects at each 
507 
site.  Statistical analysis will be performed with R-software®.  Data will be analyzed using 
508 
intention to treat principles.  Missing data will be noted.  Only the primary investigators and 
509 
research assistants will have access to study records, which will be kept in locked file cabinets in 
510 
the study investigator’s office.  All data will be entered into a database without personal health 
511 
identifiers for analysis.  Any publications or presentations will be reported without reporting 
512 
any personal health identifiers.  Any deviations from the planned statistical analysis will be 
513 
documented.  
514 
  
515 
Number of subjects and statistical power 
516 
Hemorrhage, defined as EBL greater than 500-ml, is a rare outcome that occurs in less than one 
517 
to 6.3% of D&Es above 18-weeks gestation (3-5).  Given this, a study to decrease the rate of 
518 
hemorrhage would not be feasible because it would require a large sample.   Our primary 
519 
outcome, the rate of provider intervention to decrease bleeding, represents a meaningful 
520 
clinical outcome.  When an intervention is required to prevent excessive blood loss it adds time 
521 
and expense to the procedure.  Each intervention poses some increased risk of morbidity.  
522 
Importantly, when additional interventions are required, it increases the level of concern for 
523 
the surgeon.  If our study is successful, decreasing surgical time and healthcare costs will be a 
524 
strong motivation for others to adopt this intervention.   
525 
 
526 
Though a study may have several measured outcomes, the sample size is based on the study’s 
527 
primary outcome. In this study, the primary outcome is the rate of intervention to decrease 
528 
excess blood loss.  Our primary outcome, the rate of provider intervention to decrease 
529 
bleeding, represents a meaningful clinical outcome.  When an intervention is required to 
530 
prevent excessive blood loss it adds time and expense to the procedure.  Each intervention 
531 
poses some increased risk of morbidity.  Importantly, when additional interventions are 
532 
required, it increases the level of concern for the surgeon.  We think the rate of provider 
533 
intervention is the most important factor a surgeon will consider when deciding whether to use 
534 
a medication like oxytocin.  If our study is successful, decreasing surgical time and healthcare 
535 
costs will be a strong motivation for others to adopt this intervention.   
536 
 
537 
Other outcomes we will collect data on in this study include measured blood loss, procedure 
538 
time, complications (uterine perforation, cervical or vaginal laceration, hemorrhage (blood loss 
539 
greater than 500-ml), need for transfusion, exploratory laparotomy or laparoscopy, 
540 
postoperative pain, and patient satisfaction.  Though each of these is important, the sample 
541 
size in a research study is based on the ability to demonstrate differences in the primary 
542 
outcome.    
543 
 
544 
Based on an unpublished study from Oregon Health and Science University (OHSU) that was 
545 
performed with patients in the same gestational age as proposed here, we have estimated our 
546 
baseline need for intervention to be 20% (22).  We have deemed a decrease of 15% from 20% 
547 
to 5% to represent a clinically significant change.  In other words, we are trying to show that 
548 


 
 
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16
prophylactic oxytocin will change the provider intervention rate from 20% in the unexposed 
549 
(placebo) group to 5% in the exposed (treatment) group.  A clinically significant decrease means 
550 
that the effect size is large enough to be important to physicians and patients.  Thus, we believe 
551 
that a surgeon will be willing to use a medication, in this case oxytocin, if it will decrease their 
552 
need to perform additional interventions from 20% to 5%.   
553 
 
554 
For results to be meaningful scientifically, they must also be statistically significant.  Statistical 
555 
significance is based on two parameters, power and alpha.  By convention, research studies 
556 
typically set power at 0.80 or 80% meaning there is an 80% chance of detecting a difference 
557 
between two treatments if a real difference exists and a 20% of making a false-negative 
558 
conclusion.  Alpha is conventionally set at 0.05 or 5% meaning there is a 5% chance that results 
559 
were due to chance rather than a true difference (false-positive conclusion). 
560 
 
561 
We based our sample size calculations on these conventions: power of 0.80 and alpha of 0.05.  
562 
Based on these parameters, we calculated that a sample size of 75-subjects per group is needed 
563 
to demonstrate a difference of 15%. To account for a projected 10% dropout rate, we will 
564 
randomize 83-subjects to each group for a total enrollment of 166-subjects.  If we meet our 
565 
recruitment goals, we will have the ability to demonstrate a decrease of 15% or more in the 
566 
need for interventions to decrease bleeding.   
567 
9.  Risks/Benefit Assessment 
568 
 
569 
Risk Category 
570 
This study presents minimal risk to the subjects involved.  Minimal risk is defined as "the 
571 
probability and magnitude of harm or discomfort anticipated in the research are not greater 
572 
than those ordinarily encountered in daily life or during the performance of routine physical or 
573 
psychological exams or tests."  The study involves routine venipuncture which would be done 
574 
regardless of whether an individual participated in this study.   
575 
 
576 
Any patient who undergoes a D&E is at risk for bleeding.  For patients in the treatment group, 
577 
although oxytocin has a theoretical risk of adverse events including cardiac arrythmia, water 
578 
intoxication, uterine rupture, and allergic reaction, these events are rare and have not been 
579 
documented during D&E (12-15).  These adverse events are more likely to occur to patients 
580 
who are exposed to large and/or prolonged doses of oxytocin, such as doses used for labor 
581 
induction (23, 24).  No cases of water intoxication have been reported with a single 30-unit 
582 
infusion diluted in 500-ml of IV fluid at the time of D&E.  Because oxytocin is already very 
583 
commonly used during D&E at QMC, the risk posed to the patient by this study is minimal as it 
584 
is not outside of the standard of care for this procedure. Care will be taken throughout the 
585 
surgery and in the post-operative area to identify any signs of side effects from study drug 
586 
usage.   
587 
 
588 
If bleeding occurs to patients in the placebo group, many other suitable medications and 
589 
procedures, aside from oxytocin, are readily available if needed.  Furthermore, many 
590 


 
 
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17
practitioners throughout the country do not use oxytocin routinely so the placebo protocol 
591 
would not be considered outside the current standard-of-care. 
592 
 
593 
Experiencing an unplanned pregnancy or a fetal demise can be a stressful time for a patient.  
594 
However, this study does not add any additional psychological or social risks to the subject.  The 
595 
patient will not incur any additional economical costs for study participation nor will 
596 
remuneration be provided.  Patient will be made aware that she can discontinue the study at 
597 
any time and that she will still be offered the procedure she requests.  We will utilize a data 
598 
safety-monitoring plan (DSMP) (see Section 10B) to monitor and track adverse events that may 
599 
be related to the investigation.  If this study meets criteria for an interim analysis and a review 
600 
of the data demonstrates the study posing significant risk to the subjects, we will stop the study 
601 
at that time.   
602 
 
603 
Potential Benefits 
604 
There are likely no direct benefits to the subjects who participate in this study.  Because we do 
605 
not believe that oxytocin will significantly affect bleeding during D&E, we do not think that the 
606 
treatment group will receive any direct benefits over the placebo group.  Overall, the results of 
607 
the study will help patients having D&Es in the future.  If oxytocin is ineffective at decreasing 
608 
the need for interventions to control bleeding during D&E, we can stop administering it, 
609 
thereby decreasing health care costs. If it is found to be effective, routine use of it could help 
610 
women avoid complications of excess bleeding in the future and decrease overall morbidity and 
611 
mortality associated with this procedure.  Because there is currently no established “standard 
612 
of care” regarding uterotonic use during D&Es, results from this study may help to develop 
613 
future guidelines that would direct providers in how to optimally care for their patients.  
614 
 
615 
Financial Obligations/Cost: 
616 
It will be made clear that subjects will not be billed for study drug or additional hematocrit tests 
617 
necessary to determine blood loss.  All standard of care labs, medications and procedures will 
618 
be billed through the subjects' insurance. There will be no compensation offered for injury or 
619 
adverse events of this study. 
620 
 
621 
10.  Safety & Adverse Events 
622 
 
623 
A.  Adverse Event (AE) Reporting 
624 
An adverse event is defined as any adverse finding, temporally associated with drug use.  These 
625 
findings include an abnormal physical finding or sign, a new or increased symptom, and 
626 
abnormal test or laboratory study, or a cluster of signs, symptoms, and abnormal assessments.  
627 
An unexpected adverse drug experience is defined as any adverse drug experience, the 
628 
specificity or severity of which is not consistent with the risk information described in the 
629 
general investigational plan or has been previously observed in relation to this medication. 
630 


 
 
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18
A severe adverse event is defined as any adverse drug experience occurring at any dose that 
631 
results in any of the following outcomes: death, a life-threatening adverse drug experience, 
632 
inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
633 
disability/incapacity, or a congenital anomaly/birth defect.  An unexpected adverse event is 
634 
defined as any adverse drug experience, the specificity or severity of which is not consistent 
635 
with the risk information described in the general investigational plan. Unexpected, as used in 
636 
this definition, refers to an adverse drug experience that has not been previously observed.  Any 
637 
SAE, whether or not related to the study product, will be reported to the IRB and if appropriate, 
638 
the FDA, within 24-hours. The initial SAE report will be followed by submission of a completed 
639 
SAE report. 
640 
Adverse events due to oxytocin are anticipated to be extremely unusual in this study.  Possible 
641 
AEs include, electrolyte imbalances, severe allergic reactions, and heart beat abnormalities.  Of 
642 
note, none of these adverse events have been reported during D&E procedures.  The 
643 
healthcare providers will monitor subjects for signs of adverse events during the procedure and 
644 
in the post-operative area via routine frequent vital sign assessments.  (See Section 6, 
645 
Postoperative Evaluation)  All subjects will be informed about the definitions of AEs and SAEs, 
646 
and asked to report these events during participation.  All AEs and SAEs occurring during the 
647 
course of the study will be collected, documented, and reported to the Principal Investigator on 
648 
an AE or SAE Forms. Each week, study investigators will review these forms from the previous 
649 
week for events that were reported as new or continuing. The study investigators will follow all 
650 
AEs and SAEs to the point of a satisfactory resolution.  Unanticipated non-serious adverse 
651 
events will be reported within 30 days.  All SAEs will be reported to one of the PIs within 24-
652 
hours.  
653 
 
654 
In the event that a subject is withdrawn from the study or the investigator decides to 
655 
discontinue a subject due to an SAE, the subject will have appropriate follow-up medical 
656 
monitoring. Monitoring will continue until the problem identified has resolved or stabilized with 
657 
no further change expected, is clearly unrelated to the study product, or results in death. 
658 
Outcomes of SAEs and unexpected AEs that occurred during the previous year will be included 
659 
in progress reports to the IRB.  
660 
 
661 
 
662 
B.  Data & Safety Monitoring (DSM) 
663 
The principal investigators will be primarily responsible for protecting and monitoring the 
664 
rights, safety and welfare of the subjects.  These investigators will meet regularly (i.e. weekly or 
665 
bimonthly depending on subject enrollment) with the research coordinators to monitor data 
666 
quality.   
667 
 
668 
We will create a DSMP to track and monitor any potential adverse outcomes to study subjects.  
669 
The DSM report summary will be sent to the IRB on a twice-annual basis or more frequently if 
670 
requested as part of an ongoing progress report.  Included in the DSM report will be: subject 
671 
sociodemographic characteristics, expected versus actual recruitment rates, retention rates, 
672 


 
 
Version 3 
 
 
19
any quality assurance or regulatory issues occurring during that period, summary of AEs and 
673 
SAEs, and any action or changes to the protocol since last report.  Routine documented 
674 
meetings will be held to review study progress, AEs, SAES, and update changes to the protocol 
675 
at least every six weeks.  If there is a clear trend in adverse events, unblinding can be done at 
676 
any time and the study may be terminated early if it is felt that the study poses untoward 
677 
effects on subjects.   
678 
 
679 
All Adverse Events (AE) as defined in Section 10 (Safety & Adverse Events, Page 18) occurring 
680 
during the course of the study will be collected and documented.  Each week, a study 
681 
investigator will review accumulated AE events from the previous week.  The study 
682 
investigators will follow all AEs to the point of a satisfactory resolution.  All AEs will be assessed 
683 
to determine if they meet criteria for a serious adverse event (SAE) or unexpected adverse 
684 
event (UAE), also defined in Section 10.  Any SAE or UAE will be reported to the PI (or a co-
685 
investigator if the PI is not available) within 24-hours.  
686 
 
687 
Any UAE and SAE, whether or not related to the study drug, will be reported to the DSMB 
688 
within 24 hours. The DSMB will meet at the start of the study and will reconvene after the first 
689 
10 patients have been recruited from the UH site.  Thereafter, they will meet after a total of 30 
690 
patients and 50 patients have been recruited from the UH site.  If it takes more than 6 month 
691 
intervals to reach these recruitment milestones, a meeting will be convened so that no longer 
692 
than 6 months will pass without a meeting.  If an SAE or UAE occurs, the DSMB will be 
693 
convened within a week to review the SAE or UAE.     
694 
 
695 
At scheduled meetings, the DSMB will review and evaluate accumulated study data for 
696 
participant safety, study conduct and progress, and make recommendations concerning the 
697 
continuation, modification, or termination of the trial.  As recommended by the National 
698 
Institutes of Health, the DSMB will be responsible for defining its processes, including event 
699 
triggers that would call for an unscheduled review, stopping guidelines, unmasking (unblinding) 
700 
and voting procedures prior to initiating any data review (25).  These event triggers would 
701 
include but not be limited to:  serious adverse events (see Page 18, Section 10) or a trend in 
702 
increased rates of side effects or complications to study subjects. 
703 
 
704 
Data Safety Monitoring Plan will include the following protection elements:   
705 
• Subject Safety & Protection:  No data collection activities will begin until IRB approval 
706 
has occurred. To screen for adverse events, vital signs will be continuously monitored 
707 
during the surgical procedure and patients will be frequently assessed until discharged 
708 
home (See Section 3, Postoperative Evaluation).  Subjects will be removed from the 
709 
study at any point if they request to do so or if there are any unanticipated problems 
710 
involving risks to subjects or others, unexplained adverse outcomes, or life threatening 
711 
adverse events.  Any such issues will be reported to the IRB (See Section 10, Adverse 
712 
Event Reporting).  We will still follow an intent-to-treat analysis. 
713 
 
714 
• Data Integrity:  Primary investigators will assure that subject inclusion criteria are being 
715 
met, transcription of data is accurate and complete, units of measure are recorded 
716 


 
 
Version 3 
 
 
20
appropriately, and calculations are standardized and performed accurately.  This will 
717 
occur on a biweekly or monthly schedule depending on subject enrollment. 
718 
 
719 
• Subject Privacy:  Subjects will be consented privately and in-person by the investigators 
720 
(See Section 5, Subject Recruitment, Admission, Allocation).  All questions will be 
721 
answered before subject signs consent. 
722 
 
723 
• Data Confidentiality & Study Documentation:  All subjects will be assigned a unique 
724 
study ID number. No identifying information will be used in data analysis procedures or 
725 
in research reports.  Only Principal Investigators, and research coordinator(s) involved in 
726 
the conduct of this study will have access to patient data that include personal 
727 
identifiers. Data will be recorded in a paper chart and converted into electronic file.  We 
728 
will keep paper charts in a locked drawer and password-protect electronic files. We will 
729 
keep codes linking the study identification number with the name of the subject 
730 
confidential, secured by password-protected data file within the locked research unit of 
731 
the Principal Investigator.  All information collected during this study will be kept private 
732 
to the extent allowed by federal, state and local law.  Data will be de-identified prior to 
733 
analysis.  Patient identifiers that link them to data collected during the conduct of this 
734 
study will be destroyed at the earliest possible opportunity consistent with study 
735 
conduct and applicable research regulations. Records will be destroyed by the UH-
736 
contracted shredder service when applicable. 
737 
 
738 
• Product Accountability:  The research pharmacist will be responsible for ordering, 
739 
mixing, labeling, storing, and disposing of expired/unused study drugs.  This will be done 
740 
in accordance with study specifics (see Section 6, Description of Drug to be Studied) and 
741 
will be overseen by the Primary Investigators. 
742 
 
743 
• 
Rights of Refusal and Withdrawal:  Patients will be free to refuse enrollment or 
744 
withdraw from the study at any time.  Participants may refuse to answer individual 
745 
questions posed throughout the study.   
746 
11.  Data Handling & Record Keeping 
747 
 
748 
A.  Confidentiality & Data Security 
749 
Information about study subjects will be kept confidential and managed according to the 
750 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  Those 
751 
regulations require a signed subject authorization informing the subject of the following:  
752 
i. 
What protected health information (PHI) will be collected from subjects in this study 
753 
ii. 
Who will have access to that information and why 
754 
iii. 
Who will use or disclose that information 
755 
iv. 
The rights of a research subject to revoke their authorization for use of their PHI.  
756 
 
757 


 
 
Version 3 
 
 
21
In the event that a subject revokes authorization to collect or use PHI, the investigator, by 
758 
regulation, retains the ability to use all information collected prior to the revocation of subject 
759 
authorization.  For subjects that have revoked authorization to collect or use PHI, attempts 
760 
should be made to obtain permission to collect at least vital status (i.e. that the subject is alive) 
761 
at the end of their scheduled study period. 
762 
 
763 
Consent forms are drafted and included in Appendix D.  These consent forms will be approved 
764 
by each institutions’ IRB.  The consent forms at UH (QMC), will be provided in the English 
765 
language only and therefore study will only be available to those patients with command of the 
766 
English language. Consent forms will be reviewed with each subject when they are admitted to 
767 
the study.  Subjects will be given a copy of the signed document for their records 
768 
 
769 
Hard copies of clinical information and data will always be kept in a secured place in our 
770 
research offices, and only study team members will be able to access them on an as-needed 
771 
basis.  Key personnel may not alter the data in any database without specific cause and 
772 
approval of the Investigator.  For de-identification, all subjects will be assigned a unique study 
773 
ID number when they enter the study.  Data will be recorded in a paper chart and converted 
774 
into electronic file database.  Study databases will be password protected, and all portable 
775 
devices will be fully encrypted.  No data will be sent over the Internet unless it is de-identified; 
776 
data will be sent from UW to UH but not from UH to UW.  Data will be de-identified prior to any 
777 
analysis.  We will keep codes linking the study identification number with the name of the 
778 
subject confidential, secured by password-protected data file within the locked research unit of 
779 
the Principal Investigators at each site.  Further measures to ensure data security will adhere to 
780 
security standards set by the QMC and the Research and Institutional Review Committee. 
781 
 
782 
B.  Record Retention 
783 
Study documents will be retained for at least three years after the formal discontinuation of 
784 
this project.  They will be stored in locked, secured cabinets in the PI’s office.  All data will be 
785 
de-identified.  Any electronic files will be password protected and encrypted.  If both Primary 
786 
Investigators leave Hawaii, they will make arrangements to store the data with the UH 
787 
Department of OBGYN to be destroyed at the designated time.   
788 
 
789 
C.  Direct Access to Source Data/Documents 
790 
The investigators will permit study-related monitoring, audits, RIRC review, and regulatory 
791 
inspections/audits by providing direct access to all study related data/documents.  This will be 
792 
indicated in the consent process with the potential subjects. 
793 
 
794 
12.  Ethical Considerations 
795 
 
796 


 
 
Version 3 
 
 
22
This study will be conducted according to US and international standards of Good Clinical 
797 
Practice, applicable government regulations and institutional research policies and procedures. 
798 
 
799 
This protocol and any amendments will be submitted to The Queen’s Medical Center Research 
800 
and Institutional Review Committee (RIRC) for formal approval to conduct the study.  The 
801 
decision of the RIRC concerning the conduct of the study will be made in writing to the 
802 
investigator and a copy of this decision will be provided to the sponsor before commencement 
803 
of this study. 
804 
 
805 
All subjects for this study will be provided an informed consent form describing this study and 
806 
providing sufficient information for subjects to make an informed decision about their 
807 
participation in this study.  This consent form will be submitted with the protocol for review 
808 
and approval by the RIRC for the study.  The formal consent of a subject, using the RIRC-
809 
approved consent form, must be obtained before that subject has any study procedure.  This 
810 
consent form must be signed by the subject or legally acceptable surrogate, and the 
811 
investigator-designated research professional obtaining consent. 
812 
 
813 
For other “Ethical considerations of study population,” see Section 4.   
814 
 
815 
13.  Study Finances 
816 
• Study funds from this project are through a grant from the Society of Family Planning (see 
817 
attached grant letter). These funds will go towards salaries of staff, paying for the study 
818 
drug (oxytocin), any additional blood work that is done solely to help ascertain blood loss 
819 
instead of treat patient, and all additional equipment not otherwise typically present in an 
820 
operating room and clerical necessities. (see Appendix B – Budget for more information).  
821 
All of the other healthcare costs are standard-of-care that would be billed to the patient or 
822 
her insurance regardless of whether or not she was participating in a study.  
823 
• Study funds will pay for the research medications (oxytocin) and an additional laboratory 
824 
tests (like hematocrit) that are outside the standard-of-care.  Otherwise, patient or patient’s 
825 
insurance will pay for the costs of the procedure.  
826 
• The PI or the physician performing the procedure will provide emergency medical 
827 
treatment, but the subject’s insurance will be billed for this treatment.  No other payment is 
828 
available. 
829 
• There is no remuneration being offered for the subjects.  
830 
• The PIs have no financial or personal conflict-of-interest with this study medication. 
831 
 
832 
14.  Publication & Presentation Plans 
833 
Findings from this study will be disseminated by multiple means.  Results will be presented at 
834 
the Annual Family Planning Fellowship meeting in 2015.  We plan presentation at a national 
835 
meeting such as the North American Forum on Family Planning or the Annual National Abortion 
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Federation Meeting.  This study will be submitted for publication to a nationally recognized 
837 
peer-reviewed journal such as Obstetrics & Gynecology, Contraception, or the American Journal 
838 
of Obstetrics & Gynecology.   
839 
 
840 
15.  Timeline 
841 
After IRB approval is granted, we anticipate completing recruitment and enrollment in about 
842 
12- to 14-months with data analysis to occur within a month after completion of enrollment. 
843 
Please see attached study timeline 
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16.  References 
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1. 
Pazol K, Creanga AA, Zane SB, Burley KD, Jamieson DJ, Centers for Disease C, et al. Abortion 
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surveillance--United States, 2009. Morbidity and mortality weekly report Surveillance summaries. 2012 
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Nov 23;61(8):1-44. PubMed PMID: 23169413. 
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2. 
Rolnick JA, Vorhies JS. Legal restrictions and complications of abortion: insights from data on 
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complication rates in the United States. Journal of public health policy. 2012 Aug;33(3):348-62. PubMed 
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PMID: 22622483. Epub 2012/05/25. eng. 
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3. 
Kerns J, Steinauer J. Management of postabortion hemorrhage: release date November 2012 
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SFP Guideline #20131. Contraception. 2013 Mar;87(3):331-42. PubMed PMID: 23218863. Epub 
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2012/12/12. eng. 
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evacuation: an analysis of 11,747 cases. Obstetrics and gynecology. 1983 Aug;62(2):185-90. PubMed 
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PMID: 6866362. Epub 1983/08/01. eng. 
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Laminaria and vacuum evacuation on a teaching service. The Journal of reproductive medicine. 1985 
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Aug;30(8):601-6. PubMed PMID: 4045833. Epub 1985/08/01. eng. 
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6. 
Prager SW, Oyer DJ. Second-trimester surgical abortion. Clinical obstetrics and gynecology. 2009 
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Jun;52(2):179-87. PubMed PMID: 19407524. Epub 2009/05/02. eng. 
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Lauersen NH, Conrad P. Effect of oxytocic agents on blood loss during first trimester suction 
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curettage. Obstetrics and gynecology. 1974 Sep;44(3):428-33. PubMed PMID: 4851677. Epub 
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Dildy GA, 3rd, Paine AR, George NC, Velasco C. Estimating blood loss: can teaching significantly 
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improve visual estimation? Obstetrics and gynecology. 2004 Sep;104(3):601-6. PubMed PMID: 
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10. 
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and cesarean delivery. American journal of obstetrics and gynecology. 2008 Nov;199(5):519 e1-7. 
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11. 
Guo SW, Mao X, Ma Q, Liu X. Dysmenorrhea and its severity are associated with increased 
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uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic 
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adenomyosis. Fertility and sterility. 2013 Jan;99(1):231-40. PubMed PMID: 22999795. Epub 2012/09/25. 
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12. 
Bergum D, Lonnee H, Hakli TF. Oxytocin infusion: acute hyponatraemia, seizures and coma. Acta 
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anaesthesiologica Scandinavica. 2009 Jul;53(6):826-7. PubMed PMID: 19397503. Epub 2009/04/29. eng. 
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13. 
Esteve JL, Gallego FG, Llorente MP, Bermudez SB, Sala ES, Gonzalez LV, et al. Late second-
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trimester abortions induced with mifepristone, misoprostol and oxytocin: a report of 428 consecutive 
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cases. Contraception. 2008 Jul;78(1):52-60. PubMed PMID: 18555818. Epub 2008/06/17. eng. 
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14. 
Jonsson M, Hanson U, Lidell C, Norden-Lindeberg S. ST depression at caesarean section and the 
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relation to oxytocin dose. A randomised controlled trial. BJOG : an international journal of obstetrics and 
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gynaecology. 2010 Jan;117(1):76-83. PubMed PMID: 19781043. Epub 2009/09/29. eng. 
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15. 
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delivery rooms. Obstetrical & gynecological survey. 2007 Nov;62(11):731-8. PubMed PMID: 17925046. 
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Epub 2007/10/11. eng. 
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16. 
ACOG Committee Opinion #302: Guidelines for Adolescent Health Research. Obstetrics and 
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gynecology. 2004 Oct;104(4):899-901. PubMed PMID: 15458918. Epub 2004/10/02. eng. 
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17. 
Schulz KF, Grimes DA, Christensen DD. Vasopressin reduces blood loss from second-trimester 
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dilatation and evacuation abortion. Lancet. 1985 Aug 17;2(8451):353-6. PubMed PMID: 2862514. Epub 
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1985/08/17. eng. 
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18. 
NAF. Clinical Policy Guidelines. . National Abortion Federation, 2013. 
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Keder LM. Best practices in surgical abortion. American journal of obstetrics and gynecology. 
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2003 Aug;189(2):418-22. PubMed PMID: 14520210. Epub 2003/10/02. eng. 
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Bartz D, Maurer R, Allen RH, Fortin J, Kuang B, Goldberg AB. Buccal misoprostol compared with 
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synthetic osmotic cervical dilator before surgical abortion: a randomized controlled trial. Obstetrics and 
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gynecology. 2013 Jul;122(1):57-63. PubMed PMID: 23743471. Epub 2013/06/08. eng. 
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21. 
Kan AS, Caves N, Wong SY, Ng EH, Ho PC. A double-blind, randomized controlled trial on the use 
904 
of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester 
905 
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22. 
Botha R, Micks E, Edelman A. The Effects of Sevoflurane on Blood Loss During Dilation and 
908 
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909 
Controlled trial. 2009. 
910 
23. 
In JH, Choi JW, Jung HS, Lee JA, Joo JD, Kim DW, et al. Severe hypotension and water intoxication 
911 
developed after an accidental oxytocin overdose in a morbidly obese patient undergoing cesarean 
912 
section -A case report. Korean journal of anesthesiology. 2011 Apr;60(4):290-3. PubMed PMID: 
913 
21602981. Pubmed Central PMCID: PMC3092966. Epub 2011/05/24. eng. 
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Sweeten KM, Graves WK, Athanassiou A. Spontaneous rupture of the unscarred uterus. 
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918 
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