Clinical trial NCT03640507
Conditions: Cesarean Section; Infection Surgical Site Infection
Keywords: vaginal preparation antisepsis C-section
Sponsor: Columbia University
Start date: 2018-10-01; Completion date: 2019-06-14
Enrollment: 30 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to see whether chlorhexidine is superior to povidine-iodine vaginal antisepsis at reducing bacteria colony counts in pregnant women by comparing three groups: vaginal washing with chlorhexidine-alcohol, vaginal washing with povidine-iodine, and vaginal washing with saline alone.

Detailed description:
This is a prospective trial of vaginal preparation (or vaginal cleansing/washing) on late preterm and term pregnancies admitted to Labor \& Delivery unit for cesarean delivery with three arms. Randomization allocation would be performed in 1:1:1 fashion for vaginal preparation with chlorhexidine-alcohol, povidine-iodine, and saline washes. A saline wash group is included to determine if the act of cleansing the vagina with a sponge alone reduces bacterial colony counts.

Arms: arm 1: Subjects will receive vaginal preparation with chlorhexidine-alcohol. arm 2: Subjects will receive vaginal preparation with povidine-iodine. arm 3: Subjects will receive vaginal preparation with sterile saline.
Interventions: intervention 1: Chlorhexidine-alcohol intervention 2: Povidine-iodine intervention 3: Sterile saline
Intervention descriptions: intervention 1: Intervention is a 30-second vaginal preparation or topical wash with three chlorhexidine-alcohol 0.5% solution-soaked sponge sticks. intervention 2: Intervention is a 30-second vaginal preparation or topical wash with three povidine-iodine 10% solution-soaked sponge sticks. intervention 3: Intervention is a 30-second vaginal preparation or topical wash with three sterile saline-soaked sponge sticks.

Protocol documents:
Prot_SAP_000.pdf: 
1 
IRB Submission AAAR4891 
Version 06/10/19 
Title: The effect of vaginal preparation with chlorhexidine gluconate vs. povidine-
iodine vs. saline on vaginal bacterial colony counts in pregnant women 
Study Purpose and Rationale 
Cesarean delivery is the most common major surgical procedure performed in the 
United States, with one in three babies delivered by cesarean.  Women who deliver 
by cesarean are 5 to 20 times more likely to develop postpartum endometritis than 
women who deliver vaginally.  
Those women who labor prior to cesarean delivery are at greatest risk of infectious 
complications. Although the use of prophylactic systemic antibiotics prior to 
cesarean has significantly reduced the risk of endometritis, over 10% of women 
who undergo cesarean after the onset of labor will develop postpartum 
endometritis [1, 2].  These infections may lead to extended intravenous antibiotic 
therapy for new mothers, prolonged hospital length of stay, and increased health 
care expenditures [3]. 
At present, preoperative abdominal skin antisepsis and systemic antibiotic 
prophylaxis are routinely adopted strategies to reduce postoperative infectious 
complications. Multiple studies have also examined the effect of vaginal preparation 
(or washing) with povidine-iodine prior to cesarean delivery on postpartum 
endometritis and infectious complications. A 2014 Cochrane review of seven trials 
randomizing over 2500 women found that vaginal preparation immediately prior to 
cesarean significantly reduces the rate of post-cesarean endometritis from 8.3% in 
the control group to 4.3% in the vaginal preparation group (RR 0.45, 95% CI 0.25-
0.81) with even greater effects observed in a smaller subset of women with 
ruptured membranes [4]. A review of evidence-based practices for cesarean 
delivery recommended vaginal preparation with iodine-base solution at the time of 
cesarean with a USPSTF grade of B (moderate certainty that the net benefit was 
moderate to substantial) [5]. Likewise, a 2015 review of evidence-based practices to 
reduce surgical site infections after cesarean delivery published in Infection Control 
& Hospital Epidemiology included preoperative vaginal cleansing among six 
interventions reviewed in good-quality articles with “strong” strength of evidence 
for effectiveness [6]. And finally, a recently published meta-analysis of pre-cesarean 
vaginal cleansing, which included sixteen trials of nearly 5,000 women, also found a 
significant reduction in endometritis with vaginal cleansing compared to placebo 
(RR 0.52, 95% CI 0.37-0.72). The authors concluded that preoperative vaginal 
cleansing with povidone-iodine 10% should be performed prior to all cesarean 
deliveries in women in labor and with ruptured membranes [7]. 
Despite this evidence, vaginal preparation immediate prior to cesarean delivery is 
not widely practiced.  Among 167 maternal-fetal medicine fellows who responded 
NCT03640507


 
2 
to a survey of preferred techniques at cesarean delivery in 2012, only 5% included 
pre-operative vaginal preparation among their preferences [8].   
 
In addition to increasing acceptance of this practice, questions remain about the 
best antiseptic agent for reducing microbes in the vaginal mucosa. Although the 
majority of studies published on vaginal preparation at the time of cesarean have 
used povidone-iodine solutions, there is evidence that chlorhexidine preparations 
may be superior antiseptics. A recent randomized controlled trial published in the 
New England Journal of Medicine found that chlorhexidine-alcohol was superior to 
iodine-alcohol abdominal preparations at the time of cesarean for reducing the risk 
of surgical-site infections [9].  Furthermore, povidine iodine is contraindicated in 
patients with severe iodine allergy and its antiseptic properties may be affected by 
both vaginal pH and the presence of blood [10].  
 
There is one published randomized control trial that compared povidone iodine to 
chlorhexidine for vaginal antiseptis prior to vaginal hysterectomy. Unlike vaginal 
preparation at the time of cesarean delivery, vaginal antiseptic preparation prior to 
hysterectomy in gynecological surgical is standard of care.  This study showed that 
chlorhexidine solution was more effective than povidone iodine at reducing bacteria 
colony counts in the operative field [11]. 
 
Current practices 
Vaginal preparation or washing in women undergoing cesarean who are not 
laboring or have rupture of membranes is not standard of care or indicated by 
current evidence.  A vulvar and perineal wash with povidine-iodine solution is 
routinely perfomed immediately prior to all vaginal deliveries at our institution; 
however, this is not evidence-based or protocolized.  In addition, vaginal 
preparation with povidine-iodine (or chlohexidine, according to surgeon 
preference) is standard of care prior to vaginal procedures in pregnant and 
postpartum women such as cervical cerclage, chorionic villus sampling, or dilation 
and curretage for postpartum hemorrhage.  
 
Pre-cesarean vaginal preparation is strongly supported by the current evidence 
discussed above to reduce rates of post-operative endometritis in women in labor 
or with ruptured membranes prior to cesarean. This is standard of care at certain 
institutions, and recently has been made standard of care at CHONY by instituting a 
new Perinatal Practice Guideline; however, because this is a relatively new initiative 
implementation may not yet be 100%. 
 
Purpose 
The purpose of this study is to see whether chlorhexidine is superior to povidine-
iodine vaginal antisepsis at reducing bacteria colony counts in women undergoing 
cesarean by comparing three groups: vaginal washing with chlorhexidine, vaginal 
washing with povidine-iodine, and vaginal washing with saline alone.  
 
 


 
3 
Study design 
 
This is a prospective trial of vaginal preparation (or vaginal cleansing/washing) on 
pregnancies admitted to CHONY Labor & Delivery unit for cesarean delivery with 
three arms. Randomization allocation would be performed in 1:1:1 fashion for 
vaginal preparation with chlorhexidine gluconate, povidine-iodine, and saline 
washes.  A saline wash group is included to determine if the act of cleansing the 
vagina with a sponge alone reduces bacterial colony counts.   
 
Primary outcome 
• Aerobic and anaerobic post-preparaton vaginal bacterial colony counts in 
each group 
 
Secondary outcomes 
• Baseline aerobic and anaerobic vaginal bacterial colony counts 
• Change in aerobic and anaerobic bacterial colongy counts within each group 
• Clinical infectious outcomes (although this study is not powered to detect 
these differences) 
 
Inclusion criteria (intervention groups) 
• Pregnant women admitted for cesarean delivery 
• Gestational age ≥ 34 weeks 
• Maternal age greater than or equal to 18 years 
 
Exclusion criteria (intervention groups) 
• 
Rupture of membranes or active labor  
• 
Chorioamnionitis (prior to enrollment) 
• 
Recent (within 4 weeks) antibiotic exposure 
• 
Maternal HIV infection or other known immunocompromised state 
• 
Placenta previa or accreta 
• 
Known allergy to shellfish or iodine 
• 
Known allergy to chlorhexidine gluconate 
 
Sampling (for the intervention groups these procedures will be performed in the 
operating room after anesthesia is placed) 
• Three vaginal swabs of posterior fornix (aerobic culture, anaerobic culture, 
and quantitative PCR) taken immediately prior to vaginal preparation using 
sterile technique (this will be the only step for the laboring group). 
• Vaginal preparation or wash performed over 30 seconds with three sponge 
sticks soaked in 1) low concentation chlorhexidine gluconate 0.5% solution; 
2) povidine-iodine 10%; or 3) saline, according to randomization allocation. 
• Additional three vaginal swabs of posterior fornix taken at 5-15 minutes 
after vaginal preparation is completed using sterile technique 
 
 


 
4 
Solution preparation 
• A chlorhexidine gluconate 0.5% solution will be prepared by combining 
chlorhexidine gluconate 4% solution (1 part) with normal saline, i.e. sodium 
chloride 0.9% (7 parts). 
• Povidine-iodine 10% and normal saline will be used directly as the products 
listed in the drugs/biologics section of the RASCAL IRB submission.  
 
Data collection 
• Baseline maternal demographic and pregnancy information will be collected 
at the time of sample collection (after consent is obtained) by abstraction 
from the electronic medical record 
• Retrospective chart review of maternal and neonatal infectious outcomes at 
the time of discharge and at the time of the postpartum visit. 
 
 
Statistical procedures and sample size 
 
To our knowledge, this is the first study to assess vaginal bacterial counts in 
pregnant women after an antiseptic preparation. Therefore, we have selected a 
sample size of 10 women in each group for this pilot study. 
 
Due to recent research that has shown race and ethnic-related differences in the 
vaginal microbiome of reproductive-aged and pregnant women [12, 13], our study 
will include equal numbers of Hispanic and African American women in each group.  
 
The difference in change in CFUs pre and post intervention will be compared 
between groups.   
 
 
 
 
 


 
5 
Potential risks/benefits/alternatives 
 
Risks: 
The greatest risk of participating in the study is experiencing an allergic reaction or 
localized reaction/irritation to the solution used.  
 
1) Chlorhexidine arm: 
Chlorhexidine gluconate solution has an overall low rate of adverse or allergic 
reactions. All women undergoing non-emergent cesarean delivery at our institution 
receive abdominal preparation with chlorhexidine-alcohol (unless there is a known 
allergy) consistent with current evidence of its effectiveness and safety [9]. 
Chlorhexidine gluconate is not FDA-approved for use on mucosal surfaces.  
However, chlohexidine with low concentrations of alcohol (4% or less) are safe and 
effective for vaginal use.  The off-label use of chlorhexidine solutions for vaginal 
preparation is supported by the American College of Obstetricians and 
Gynecologists in the setting of iodine allergy or surgeon preference [14]. At our 
institution, chlorhexidine vaginal preparation is routinely used at the time of 
gynecologic surgery according to surgeon preference. In addition, chlorhexidine-
based mouthwashes are approved for use on oral mucosal surfaces in the treatment 
of gingivitis and periodontitis.  
 
Of note, there is an FDA warning from February 2017 of rare but serious allergic 
reactions to skin antisepsis with chlorhexidine gluconate.  However, this has not to 
our knowledge been reported with vaginal preparation, which generally uses a 
much lower concentation of chlorhexidine.  There have been numerous large 
prospective published studies on chlohexidine vaginal washing or irrigation in 
thousands of laboring pregnant patients (these studies had different research aims 
and therefore are not included under the study purpose and rationale) with no 
reported adverse effects [15-19]. 
 
2) Povidine-iodine arm 
Povidine-iodine has an overall low rate of adverse or allergic reactions.  In seven 
trials randomizing over 2800 women to povidine-iodine vaginal preparation prior 
to cesarean delivery, there were no reported side effects [4].  However, vaginal 
irritation or reaction is a possible side effect. All pregnant women undergoing 
vaginal procedures (such as chorionic villus sampling or cervical cerclage) receive 
vaginal preparation with povidine-iodine.  In addition, it is routinely used in 
gynecologic procedures and surgery according to surgeon preference.  
 
3) Saline arm 
There is minimal risk with a vaginal saline wash. Localized irritation or minor 
discomfort may be possible due to sponge stick washing.  
 
Finally, for all three arms, there is the potential risk of loss of confidentiality of 
sensitive health information, however this is unlikely. A code number will be used to 
separate data, biological samples, and health information from the participant’s 


 
6 
name and other potential identifiers. The research file that links the code number to 
the patient’s name will be kept in a locked cabinet, encrypted data file, or password-
protected computer, and only the investigator and authorized study staff will have 
access to the file. 
 
Benefits: 
There are no personal or direct benefits from taking part in this study. However, the 
information collected from this research may help others in the future. 
 
Alternatives: 
Women may decline to participate in the study and undergo routine care on labor 
and delivery. Declining to participate will not impact their pregnancy, intrapartum 
or postpartum care. 
 
Compensation: 
The thirty participants undergoing vaginal preparation in the study will receive $50 
in cash for their time and effort.  
 
 
 
 
 


 
7 
References 
 
1. 
Smaill, F.M. and R.M. Grivell, Antibiotic prophylaxis versus no prophylaxis for 
preventing infection after cesarean section. Cochrane Database Syst Rev, 
2014(10): p. CD007482. 
2. 
Hammad, I.A., et al., Peripartum complications with cesarean delivery: a review 
of Maternal-Fetal Medicine Units Network publications. J Matern Fetal 
Neonatal Med, 2014. 27(5): p. 463-74. 
3. 
Blumenfeld, Y.J., et al., Risk Factors for Prolonged Postpartum Length of Stay 
Following Cesarean Delivery. Am J Perinatol, 2015. 32(9): p. 825-32. 
4. 
Haas, D.M., S. Morgan, and K. Contreras, Vaginal preparation with antiseptic 
solution before cesarean section for preventing postoperative infections. 
Cochrane Database Syst Rev, 2014(12): p. CD007892. 
5. 
Dahlke, J.D., et al., Evidence-based surgery for cesarean delivery: an updated 
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6. 
McKibben, R.A., et al., Practices to Reduce Surgical Site Infections Among 
Women Undergoing Cesarean Section: A Review. Infect Control Hosp 
Epidemiol, 2015. 36(8): p. 915-21. 
7. 
Caissutti, C., et al., Vaginal Cleansing Before Cesarean Delivery: A Systematic 
Review and Meta-analysis. Obstet Gynecol, 2017. 
8. 
Dahlke, J.D., et al., Preferences in cesarean delivery surgical technique: a survey 
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9. 
Tuuli, M.G., et al., A Randomized Trial Comparing Skin Antiseptic Agents at 
Cesarean Delivery. N Engl J Med, 2016. 374(7): p. 647-55. 
10. 
Mangram, A.J., et al., Guideline for prevention of surgical site infection, 1999. 
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11. 
Culligan, P.J., et al., A randomized trial that compared povidone iodine and 
chlorhexidine as antiseptics for vaginal hysterectomy. Am J Obstet Gynecol, 
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12. 
Ravel, J., et al., Vaginal microbiome of reproductive-age women. Proc Natl Acad 
Sci U S A, 2011. 108 Suppl 1: p. 4680-7. 
13. 
Stout, M.J., et al., Early pregnancy vaginal microbiome trends and preterm 
birth. Am J Obstet Gynecol, 2017. 
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American College of, O., P. Gynecologists Women's Health Care, and P. 
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p. 166-70. 
16. 
Rouse, D.J., et al., Chlorhexidine vaginal irrigation for the prevention of 
peripartal infection: a placebo-controlled randomized clinical trial. Am J 
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