The Association Between Postpartum Aspirin Use and NT-proBNP Levels as a Marker for Maternal Health Outcomes.
Phase: PHASE4
Conditions: Blood Pressure
Sponsor: Duke University

Standard Research Summary
Purpose of the Study
Objectives & hypotheses to be tested
Specific Aim 1: To compare NT-proBNP levels at 4-6 weeks postpartum between patients continued on 6 
weeks of aspirin use postpartum and placebo.
Our hypothesis is that NT-proBNP levels will be lower in the group randomized to continuation of aspirin 
for 6 weeks’ postpartum. As we know that aspirin use during pregnancy decreases preeclampsia risk and 
that preeclampsia in itself is a risk factor for long-term cardiovascular disease in our patient population, we 
anticipate that the continuation of aspirin in the postpartum setting decreases cardiac strain and that 
patients continued on maintenance aspirin dosing will have lower NT-proBNP levels at 4-6 weeks 
postpartum. 
Specific Aim 2: To compare average blood pressure readings at the 4-6 week postpartum visits as well as 
hospital readmission rates for blood pressure monitoring or cardiovascular concerns in the 4-6 week 
postpartum period between groups.
We plan to evaluate if patients continued on aspirin for 6 weeks postpartum have lower hospital 
readmission rates than patients on placebo. This could support prior data that showed that prenatal aspirin 
use was associated with decreased incidence of postpartum hypertension following delivery and decreased 
rates of hospital readmission.
Background & Significance
Should support the scientific aims of the research
General Information
*Please enter the full title of your protocol:
The association between postpartum aspirin use and NT-proBNP levels as a marker for 
maternal health outcomes: a randomized-controlled trial
*Please enter the Short Title you would like to use to reference the study:
Postpartum ASA and NT-proBNP
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this
study.
Approval Date: 05/01/2024
NCT05889468
DUHS IRB Application (Version 1.6)

Preeclampsia is a hypertensive disorder of pregnancy that affects 2-8% of all pregnancies and is a leading 
cause of maternal and neonatal morbidity and mortality worldwide.
 Maternal complications associated 
1-2
with preeclampsia include stroke, seizure, permanent end organ damage, and maternal death. 
Importantly, preeclampsia is also a defined risk factor for future cardiovascular morbidity and mortality 
and has been associated with increased long-term risk of chronic hypertension, cardiovascular disease, 
and death.
 Neonatal complications include preterm delivery and associated complications, intrauterine 
3-4
growth restriction, placental abruption, and intrauterine fetal demise.  While the exact etiology of 
1
preeclampsia is unknown, prior studies have suggested the imbalance in prostacyclin and thromboxane A2 
(TXA2) metabolism as a contributing factor.
 For this reason, aspirin was targeted as potential 
 5-6
intervention for the prevention of preeclampsia.
Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) that acts primarily on cyclooxygenase 
isoenzymes 1 and 2 (COX-1 and COX-2) to regulate prostacyclin production. At lower doses (60-150 mg
/day), ASA selectively acts on COX-1, thereby inhibiting TXA2 secretion without affecting the secretion of 
endothelial prostacyclin.
 This results in a vasodilatory effect and in the reduction of platelet 
7-8
aggregation, which is thought to improve placental perfusion and decrease the incidence of preeclampsia.  
9
ASA has also been recommended by the USPSTF as primary prevention of cardiovascular disease in at-risk 
individuals 40-59 years of age as well as secondary prevention in survivors of cardiovascular occlusive 
events.10
Interventions aimed to reduce the incidence of preeclampsia are paramount to public health given the 
short- and long-term implications associated with the diagnosis. Unfortunately, hospital admission rates 
involving a diagnosis of a hypertensive disorder are increasing and have been associated with higher rates 
of acute renal failure, disseminated intravascular coagulation syndrome, pulmonary edema, 
cerebrovascular disorders, and overall maternal morbidity and mortality.
 Additioally, a systematic review 
11
and meta-analysis by Wu et al evaluated future risk of cardiovascular disease in patients diagnosed with 
preeclampsia during pregnancy and found that preeclampsia was associated with a 4-fold increase in the 
incidence of future heart failure and a 2-fold increase in incidence of coronary artery disease, 
cerebrovascular accidents, and death.
 The American Heart Association now considers a history of 
12
preeclampsia a risk factor for development of future cardiovascular disease and targets these populations 
as “at risk” individuals who may benefit from lifestyle modifications to lower their risk of heart disease.
Fo
13
r this reason, annual medical reviews are recommended life-long for patients with a history of 
preeclampsia, and further research is needed into prevention to decrease maternal morbidity and mortality.
14
Administration of low-dose aspirin has been demonstrated to decrease the risk of development of 
preeclampsia in high-risk patients, defined by the National Institute for Health and Care Excellence (NICE) 
guidelines as any patient with a history of hypertensive disorders of pregnancy, chronic kidney disease, 
autoimmune disease, chronic hypertension, first pregnancy, age >40 years, pregnancy interval >10 years, 
BMI>35, multiple gestation, or family history of preeclampsia.
 For this reason, both the USPSTF and the 
15
WHO recommend administration of low dose aspirin in patients with one high risk or multiple moderate 
risk factors for preeclampsia.
Initiation of aspirin is recommended between 12 and 28 weeks, ideally 
16-17 
before 16 weeks, as a recent meta-analysis demonstrated only a modest reduction in preeclampsia when 
aspirin was started after 16 weeks but a significant reduction in preeclampsia and intrauterine growth 
restriction if initiated before this gestational age.
 ACOG recommends continuation of aspirin until 
18
delivery.1
A recent study by Christenson et al studying patients with preeclampsia on aspirin prevention found that 
prenatal aspirin use was associated with a decreased incidence of postpartum hypertension within 48 
hours after delivery and decreased rates of 6-week hospital readmission.
Currently, there is no known 
19 
role for continuation of aspirin in the postpartum period in at-risk patients and studies on the subject are 
limited.
While there are no definitive serum markers that can predict or diagnose preeclampsia, several have been 
studied as diagnostic tools. B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide 
(NT-proBNP) are included. Resnik et al studied B-type natriuretic peptide (BNP) levels in 118 pregnant 
patients from first trimester to term gestation. In this study, patients with preeclampsia with severe 
features had significantly higher BNP levels than both patients with preeclampsia without severe features 
(P<0.01) or patients without hypertensive disorders of pregnancy (<0.01). They established a BNP cut-off 
of <40.6 as having a negative predictive value of 92% in excluding preeclampsia during pregnancy.
 A 
20
2013 systematic review supported this conclusion and found that patients with preeclampsia had 
significantly higher BNP in the third trimester, which was thought to be indicative of cardiovascular 
dysfunction associated with preeclampsia.
 Additionally, BNP and NT-proBNP are currently widely used 
21
biomarkers for the diagnosis of heart failure and cardiovascular disease and risk-stratification for 
cardiovascular disease and long-term morbidity and mortality outside of pregnancy.22-24

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Notably, however, there is no established “normal” BNP or NT-proBNP level during pregnancy or 
postpartum. Denoble et al compared NT-proBNP levels between obese and non-obese women throughout 
pregnancy at our institution and found that while NT-proBNP levels were lower in obese subjects during 
pregnancy, the difference was not significant in the postpartum setting.
 In this study, the postpartum 
25
NT-proBNP in the obese population was 33 (27-56) and non-obese population was 23 (8-42).
 Finally, 
25
Sheikh et al performed a meta-analysis of available literature on BNP and NT-proBNP levels during 
pregnancy and postpartum and found that both biomarkers are useful diagnostic tools for cardiac 
complications in both pregnant and recently delivered patients.26
There is currently no information on continuation of low-dose aspirin after delivery. However, the use of 
aspirin both during pregnancy in patients at risk for development of preeclampsia as well as for 
cardiovascular disease prophylaxis in high-risk patients outside of pregnancy suggests a possible 
protective benefit. With maternal morbidity and mortality increasing in the United States and 
cardiovascular disease being the number one cause, a better understanding of protective interventions 
against cardiac strain is paramount. This study hopes to evaluate the use of aspirin as a low-cost and 
accessible means to decrease long-term adverse maternal health outcomes. Evaluation of postpartum NT-
proBNP levels in the postpartum period can help shed light on this important topic.
References:
American College of Obstetricians and Gynecologists. Practice bulletin no. 222: Gestational 
hypertension and preeclampsia. Obstet Gynecol 2020;135:e237-60.
Jeyabalan A. Epidemiology preeclampsia: impact of obesity. Nutr Rev. 2013;71(0_1).
Leslie MS, Briggs LA. Preeclampsia and the risk of future vascular disease and mortality: a review. J 
Midwifery Womens Health. 2016;61(3):315-24.
Funai EF, Friedlander Y, Paltiel O, Tiram E, Xue X, Deutsch L, Harlap S. Long-term mortality after 
preeclampsia. Epidemiology. 2005;16(2):206-15.
Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, et al. Effect of low-dose 
aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for 
pregnancy-induced hypertension. N Engl J Med 1989;321:357–62.
Schiff E, Peleg E, Goldenberg M, Rosenthal T, Ruppin E, Tamarkin M, et al. The use of aspirin to 
prevent pregnancy-induced hypertension and lower the ratio of thromboxane A2 to prostacyclin in 
relatively high risk pregnancies. N Engl J Med 1989;321:351–6
Clarke RJ, Mayo G, Price P, FitzGerald GA. Suppression of thromboxane A2 but not of systemic 
prostacyclin by controlled-release aspirin. N Engl J Med 1991;325:1137–41.
Patrono C. Aspirin as an antiplatelet drug. N Engl J Med 1994;330:1287–94.
Atallah A, Lecarpentier E, Goffinet F, Doret-Dion M, Gaucherand P, Tsatsaris V. Aspirin for 
prevention of preeclampsia. Drugs 2017;77(17):1819-1831.
USPSTF Recommendation Statement. Aspirin use to prevent cardiovascular disease. JAMA. 2022;
327(16):1577-1584.
Kuklina EV, Ayala C, Callaghan WM. Hypertensive disorders and severe obstetric morbidity in the 
United States. Obstet Gynecol. 2009;113(6):1299-1306.
Wu P, Haththotuwa R, Shing Kwok C, Babu A, Kotronias RA, Ruston C, et al. Preeclampsia and 
future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual 
Outcomes. 2017;10:e003497
Seely EW, Tsigas E, Rich-Edwards JW. Preeclampsia and future cardiovascular disease in women: 
How good are the data and how can we manage our patients? Semin Perinatol. 2015;39(4):276-83.
Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive 
disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for 
international practice. Hypertension. 2018;72(1):24-43.
Force USPST. Final Update Summary: Low-Dose Aspirin Use for the Prevention of Morbidity and 
Mortality From Preeclampsia: Preventive Medication U.S. Preventative Services Task Force. 2016. 
Available from: https://www.uspreventiveservicestaskforce.org/Page/Document
/UpdateSummaryFinal/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-
.
mortality-from-preeclampsia-preventive-medication
Henderson JT, Whitlock EP, O’Connor E, Senger CA, Thompson JH, Rowland MG. Low-dose aspirin 
for prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the 
U.S. Preventive Services Task Force. Ann Intern Med. 2014;160:695–703.
World Health Organization, Department of Reproductive Health and Research, Department of 
Maternal, Newborn, Child and Adolescent Health, and Department of Nutrition for Health and 
development. WHO recommendations for prevention and treatment of preeclampsia and eclampsia, 
World Health Organization, 2011.
Roberge S, Nicolaides K, Demers S, Hyett J, Chaillet N, Bujold E. The role of aspirin dose on the 
prevention of preeclampsia and fetal growth restriction: systematic review and meta-analysis. Am J 
Obstet Gynecol 2017;216:110-20.
Christenson E, Stout MJ, Williams D, Verma AK, Davila-Roman VG, Lindley KJ. Prenatal low-dose 
aspirin use associated with reduced incidence of postpartum hypertension among women with 
preeclampsia. Am J Perinatol. 2021. Doi:10.1055/s-0041-1728826.

20.  
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28.  
Resnik JL, Hong C, Resnik R, Radmila K, Beede J, Bhalla V, Maisel A. Evaluation of B-type 
natriuretic peptide (BNP) levels in normal and preeclamptic women. Am J Obstet Gynecol. 2005;193
(2):450-454.
Afshani N, Moustaqim-Barrette A, Biccard BM, Rodseth RN, Dyer RA. Utility of B-type natriuretic 
peptides in preeclampsia: a systematic review. Int J Obstet Anesth. 2013;22(2):96-103.
Cao Z, Jia Y, Zhu B. BNP and NT-proBNP as diagnostic biomarkers for cardiac dysfunction in both 
clinical and forensic medicine. Int J Mol Sci. 2019;20(8):1820.
Angelantonio ED, Chowdhury R, Sarwar N, et al. B-type natriuretic peptides and cardiovascular 
risk: systemic review and meta-analysis of 40 prospective studies. Circulation. 2009;120:2177-
2187.
Stewart RAH, Kirby A, White HD, et al. B-type natriuretic peptide and long-term cardiovascular 
mortality in patients with coronary heart disease. JAHA. 2022;11:e024616.
Denoble A, Moyett J, Goldstein S, Ward CC, Truong T, Erkanli A, James A. Grotegut C. Prospective 
observational study of amino-terminal brain natriuretic peptide levels in obese and non-obese 
women during pregnancy. Am J Perinatol. 2022; doi: 10.1055/a-1925-1532. 
Sheikh M, Ostadrahimi P, Salarzaei M, Parooie F. Cardiac complications in pregnancy: a systematic 
review and meta-analysis of diagnostic accuracy of BNP and N-Terminal Pro-BNP. Cardiol Ther. 
2021;10(2):501-514.
Aziz A, Bello N. (2018, September 12 - ). Postpartum low-dose aspirin and preeclampsia. Identifier: 
NCT03667326. https://clinicaltrials.gov/ct2/show/NCT03667326?
.
cond=postpartum+aspirin&draw=2&rank=2
Shahul S, Fox EH. (2020, July 21 - ). Aspirin and preeclampsia. Identifier: NCT04479072. https://
.
clinicaltrials.gov/ct2/show/NCT04479072?cond=postpartum+aspirin&draw=2&rank=3
Design & Procedures
Describe the study, providing details regarding the study intervention (drug, device, physical 
procedures, manipulation of the subject or the subject’s environment, etc.). Discuss justifications for 
placebo control, discontinuation or delay of standard therapies, and washout periods if applicable. 
Identify procedures, tests and interventions performed exclusively for research purposes or more 
frequently than standard of care. Include alternative therapies, concurrent therapies discontinued per 
protocol, risk benefit ratio, and use of tissue/specimens. Discuss monitoring during washout periods if 
applicable. Include brief description of follow-up, if any.
This is a randomized-controlled trial of comparing NT-proBNP levels at 4-6 weeks postpartum between 
patients randomized to continuation of postpartum aspirin 81 mg for 6 weeks postpartum and placebo. 
Patients meeting inclusion criteria will be approached during routine prenatal visits, on arrival to Labor and 
Delivery, or following delivery for enrollment. Informed consent will be obtained, and patients will be 
randomized in a 1:1 fashion to aspirin 81 mg vs identical-appearing placebo to be continued for 6 weeks’ 
postpartum. Patients will receive these medications prior to hospital discharge. Patients will  be scheduled 
for routine postpartum follow-up appointment at 4-6 weeks as is standard of care at Duke. Patients will be 
reminded of their appointment via telephone call or text message the day prior to their scheduled follow-
up visit. NT-proBNP levels will be drawn at the 4-6-week postpartum visit. This will b e one blood draw 
with a total of 10 mL collected. NT-proBNP levels will be compared between groups.
Patients will be eligible for randomization if they are 18 years of age or older, English-speaking, 
postpartum, have met USPSTF recommendations for low-dose aspirin use during pregnancy:
1 high risk 
>
factor (history of preeclampsia in prior pregnancy, multifetal gestational, chronic hypertension, preexisting 
diabetes, renal disease, autoimmune disease) or
2 moderate risk factors (nulliparity, obesity, family 
>
history of preeclampsia, sociodemographic characteristics, age 35 years or older, or personal history 
factors) and reported at least 50% compliance with aspirin during pregnancy. Patients will be excluded if 
they have had a hypersensitivity reaction to aspirin or other salicylates, history of gastrointestinal 
bleeding, history of gastric or duodenal ulcers, severe hepatic dysfunction, bleeding disorders and 
diathesis, known cardiac dysfunction with reduced ejection fraction, or are taking or prescribed ACE 
inhibitors. Patients requiring ICU admission during their pregnancy will be excluded.
Patients will be randomized in a 1:1 fashion to aspirin 81 mg vs identical-appearing placebo to be 
continued for 6 weeks’ postpartum using a block randomization scheme implemented in RedCap.    
The primary outcome for this analysis will be 4-6 week postpartum NT-proBNP levels. Secondary outcomes 
will be rates of preeclampsia diagnosis postpartum, rates of eclampsia, hospital readmission rates for 
blood pressure monitoring or cardiovascular disease work-up indications, number of subjects requiring 
initiation or increase in blood pressure medications, hospital readmission rates for bleeding-related 
complications, and rates of blood transfusions.

Selection of Subjects
List inclusion/exclusion criteria and how subjects will be identified.
Patients will be eligible for randomization if they are 18 years of age and older, English-speaking, 
postpartum, have met USPSTF recommendations for low-dose aspirin use during pregnancy: 
1 high risk 
>
factor (history of preeclampsia in prior pregnancy, multifetal gestational, chronic hypertension, preexisting 
diabetes, renal disease, autoimmune disease) or 
2 moderate risk factors (nulliparity, obesity, family 
>
history of preeclampsia, sociodemographic characteristics, age 35 years or older, or personal history 
factors) and reported at least 50% compliance with aspirin during pregnancy. 
Patients will be excluded if they have had a hypersensitivity reaction to aspirin or other salicylates, history 
of gastrointestinal bleeding, history of gastric or duodenal ulcers, severe hepatic dysfunction, bleeding 
disorders and diathesis, known cardiac dysfunction with reduced ejection fraction, or are taking or 
prescribed ACE inhibitors. Patients who required ICU level care during their pregnancy will be excluded.
Subject Recruitment and Compensation
Describe recruitment procedures, including who will introduce the study to potential subjects. Describe 
how you will ensure that subject selection is equitable and all relevant demographic groups have access 
to study participation (per 45 CFR 46.111(a) (3)). Include information about approximately how many 
DUHS subjects will be recruited. If subjects are to be compensated, provide specific prorated amounts 
to be provided for expenses such as travel and/or lost wages, and/or for inducement to participate.
Patients will be approached for enrollment based on their eligibility in clinic, on admission to Labor and 
Delivery, or following delivery at Duke University. All patients who deliver at Duke University Hospital will 
be eligible for screening. Study staff will approach the subject and provide information regarding the 
study. If the patient is interested in participating, then study staff will obtain informed consent at that time.
The total goal enrollment is 114 participants (57 in each group). Patients will receive a $10 dollar gift 
certificate at their postpartum visit for participation in our study.
Subject’s Capacity to Give Legally Effective Consent
If subjects who do not have the capacity to give legally effective consent are included, describe how 
diminished capacity will be assessed. Will a periodic reassessment occur? If so, when? Will the subject 
be consented if the decisional capacity improves?
We will not be including patients that do not have the capacity to give legally effective consent.
Study Interventions
If not already presented in #4 above, describe study-related treatment or use of an investigational 
drug or biologic (with dosages), or device, or use of another form of intervention (i.e., either physical 
procedures or manipulation of the subject or the subject’s environment) for research purposes.

The treatment group will be provided with a 6-week supply of 81 mg of aspirin prior to discharge from the 
delivery admission. The control group will receive a 6-week supply of placebo medication from the 
Investigational Pharmacy prior to discharge. The placebo will be identically appearing to the 81 mg aspirin. 
Patients will be scheduled for a 4-6 week postpartum clinic appointment, which is standard for these 
patients outside of this proposal. 
Risk/Benefit Assessment
Include a thorough description of how risks and discomforts will be minimized (per 45 CFR 46.111(a) (1 
and 2)). Consider physical, psychological, legal, economic and social risks as applicable. If vulnerable 
populations are to be included (such as children, pregnant individuals, imprisoned persons or 
cognitively impaired adults), what special precautions will be used to minimize risks to these subjects? 
Also identify what available alternatives the person has if he/she chooses not to participate in the 
study. Describe the possible benefits to the subject. What is the importance of the knowledge expected 
to result from the research?
The use of low-dose aspirin during pregnancy has not been associated with a significantly increased risk of 
hemorrhage during the delivery course, and this dosage would not be expected to result in increased 
bleeding risk in the postpartum period.
While low-dose aspirin side effects are typically mild, patients may experience some, all, or none of the 
side effects listed below. Side effects will be assessed at the 4-6 week postpartum visit.
Mild indigestion
Nausea
Vomiting
Heartburn
Increased bleeding tendency
Nosebleeds
Bleeding gums
Stomach ulcers
Wheezing
Difficulty breathing
Anaphylaxis
Given the overall minimal side effects associated with the use of low-dose aspirin as well as its routine use 
during pregnancy in a large subset of patients, identification of risk-mitigating interventions for long-term 
cardiovascular disease may improve long-term maternal health outcomes.
Low-dose aspirin is considered safe during breastfeeding. After aspirin ingestion, salicylic acid is excreted 
in breastmilk, with increasing levels detected with increased doses. With low doses of aspirin, defined as 
75 to 325 mg daily, aspirin is not excreted in breast milk and salicylate levels are low. Therefore, low-dose 
aspirin is safe to administer in breastfeeding mothers.
There is also a small risk of loss of confidentiality and risk associated with a blood draw.
Costs to the Subject
Describe and justify any costs that the subject will incur as a result of participation; ordinarily, subjects 
should not be expected to pay for research without receiving direct benefit.
There is no anticipated cost to patients.
Data Analysis & Statistical Considerations
Describe endpoints and power calculations. Provide a detailed description of how study data will be 
analyzed, including statistical methods used, and how ineligible subjects will be handled and which 
subjects will be included for analysis. Include planned sample size justification. Provide estimated time 

to target accrual and accrual rate. Describe interim analysis including plans to stop accrual during 
monitoring. Phase I studies, include dose escalation schema and criteria for dose escalation with 
definition of MTD and DLT.
Baseline characteristics will be summarized by control and intervention group. Continuous variables will be 
summarized using mean (standard deviation) or median (25
 percentile, 75
 percentile) while categorical 
th
th
variables will be summarized using frequency (percentage). Primary outcome, NT-proBNP levels at 4-6 
weeks postpartum, will be summarized and compared between groups using two-sample t-test or Wilcoxon 
rank sum test, depending on the empirical distribution of the data. Secondary outcomes will be compared 
between groups using the chi-square, Fisher’s exact, Mann Whitney U, or student’s t-tests, as appropriate. 
A p-value of M0.05 will be considered significant. Analyses will be performed in R 4.2.0 (R Core Team, 
2022) or SAS 9.4 (SAS Institute Inc., Cary, NC).
A prior study at our institution found the following NT-proBNP levels in patients with and without obesity at 
4-6 weeks postpartum:
NT-proBNP at 4-6 weeks postpartum
Mean (SD)
37.4 (32.2)
   Median
30.5
   Q1, Q3
11.0, 47.0
   Range
(2.5-135.0)
Using this mean and standard deviation with a target power of 0.8 at 0.05 level of significance, we 
calculated a sample size of 90 to detect a medium effect size (Cohen’s d = 0.6), which is equivalent to a 
difference of 19.3 between control and intervention. To account for a 20% drop-out rate, we calculated a 
sample size of 114 (57 in each group).
This study is designed to be performed within a 24-month timeframe. Patient enrollment will start in spring 
2023. Trained research staff will enroll patients in the clinic, on Labor and Delivery and postpartum with 
the goal to meet our sample size for enrollment by spring 2024.
Data & Safety Monitoring
Summarize safety concerns, and describe the methods to monitor research subjects and their data to 
ensure their safety, including who will monitor the data, and the frequency of such monitoring. If a 
data monitoring committee will be used, describe its operation, including stopping rules and frequency 
of review, and if it is independent of the sponsor (per 45 CFR 46.111(a) (6)).
A Data Monitoring Committee (DMC) will be created to perform regular and timely review of data semi-
annually in order to identify early, significant benefit or harm for patients while the trial is in 
progress.  Non-identified safety data will be communicated to the DMC who will then meet to review the 
data.  The DMC will be composed of three faculty members within the Duke University Department of 
Gynecology and Obstetrics. Individuals who are investigators or co-investigators cannot be 
members.  Members must have no financial, scientific, or other conflicts of interest with the study. All 
investigators understand that the DMC serves as additional human subject’s protection, but does not 
supplant reporting of significant adverse events to the Duke IRB. The DMC may devise its own stopping 
rules, and if there are significant numbers of adverse events, the DMC will recommend continuation, 
modification, or termination of the study after each meeting.  This recommendation will be communicated 
to the Principle investigator who is responsible for reviewing the recommendation and forwarding it to the 
IRB. All investigators understand that the DMC may recommend their own "stopping rule" if other events 
occur which indicate a significant risk to study subjects.