Preterm Labor Prevention Using Vaginal Antiseptics Prior to 16 Weeks of Gestation

NCT ID: NCT05944094

Last Updated: 2023-07-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1117 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2023-06-16

Brief Summary

The aim of this prospective observational study was to evaluate the efficacy of a universal strategy of primary prevention of preterm birth using intravaginal chlorhexidine (CLX) applied before 16 weeks.

The main question is whether universal treatment with vaginal CLX before 16 weeks would reduce the incidence of preterm birth, especially before 34 weeks.

Participants were recruited at the routine first trimester consultation. All patients underwent an initial ultrasound examination between 6+0 and 15+6 weeks gestation, including assessment of embryo/fetus vitality.

Antiseptic treatment aimed at reducing possible bacterial overgrowth consisted of 10 days (1 box) of CLX vaginal ovules (CLX digluconate 0.2%) always starting between 9+0 and 16+0 weeks.

As this product is widely marketed and frequently indicated in gynaecology, we did not deprive the non-treated group of treatment because we wanted to assess whether it could have an effect on reducing preterm delivery.

The pregnant women were then followed up until the end of pregnancy and compared with a cohort of patients who had not received any treatment.

All data related to delivery were collected, as well as any events related to preterm delivery, such as onset of contractions, cervical shortening and premature rupture of membranes, regardless of final gestational age at delivery.

Detailed Description

Clinical implications of the study:

The clinical implications of our project would be to counteract the effect of pathogenic bacteria from the beginning of pregnancy (outside the teratogenic period) with the administration of the CLX ovules and thus enhance the action of the normal vaginal microbiota in the pregnant patient, since the glycogen available due to hormonal action favours the growth and development of lactobacillus, responsible for its protective activity against pathogens during pregnancy.

Sample size:

The approximate number of births per year in Spain is 370,000. The minimum number of patients to be recruited would be 400 with a 95% confidence interval.

Patients were recruited as they attended the consultation where the PI and/or collaborators were present.

Variables:

• maternal age,
• parity,
• Gestational age (GA) at examination in weeks,
• GA at delivery in weeks,
• Interval between ultrasound and delivery,
• Birth weight (BW), BW centile,
• fetal gender,
• onset of labor (elective cesarean section, induction of labor and spontaneous onset of labor),
• mode of delivery (cesarean section for abnormal cardiotocography, failure to progress or elective, assisted delivery and spontaneous delivery),
• Apgar scores at 5 minutes,
• neonatal cord arterial hydrogen potential( pH)
• Newborn destination: ward, neonatal, neonatal intensive care unit
• Type of event triggering preterm birth:Premature rupture of membranes /Uterine dynamics + cervical modifications

Statistical analysis Continuous variables were presented as mean and standard deviations (SD), median and interquartile range (IQR), while categorical variables were presented as absolute numbers and relative frequencies. Characteristics between both cohorts were compared by mean of Mann- Whitney and Fisher tests. Finally, to assess the validity of results and ensure consistency an additional multivariable analysis was performed adjusting for clinical parameters, to evaluate the odds ratio (OR) of the different determinants in the prediction of preterm birth. Finally, preterm birth incidence was calculated for specific groups selected according to the multivariable analysis result. Statistical analysis and graphs were done using Graph Pad Prism®, Mac version 9.0.1, and Stat Plus® Mac Pro version 8.0.1.s. Permissions were obtained from La Fe hospital review board and from the Valencian Autonomic Government health authorities (reference: PLUVA, date 4-2-2021). Written informed consent was retrieved to participate in the study. The authors report no conflicts of interest.

Quality control:

All analyses were performed on a single sample of patients who met the selection criteria and who had all the information required for the variables to be analysed.

In cases where it was not possible to obtain this information, the following were excluded from the study

Conditions

Preterm Birth

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1: exposed patients

Group 1: pregnant women who received intravaginal chlorhexidine before 16 weeks of gestation Group 2: pregnant women who did not received intravaginal chlorhexidine e before 16 weeks of gestation

Clorhexidine

Intervention Type: DEVICE

Antiseptic treatment aimed at reducing potential bacterial overgrowth consisted of 10 days (1 box) of vaginal ovules of CLX (CumLaude CLX ® , CLX digluconate 0.2%) always starting between 10+0 and 16+0 weeks.

Interventions

Clorhexidine

Antiseptic treatment aimed at reducing potential bacterial overgrowth consisted of 10 days (1 box) of vaginal ovules of CLX (CumLaude CLX ® , CLX digluconate 0.2%) always starting between 10+0 and 16+0 weeks.

Intervention Type: DEVICE

Other Intervention Names

Code GMDN (Global Medical Device Nomenclature): 47673 - Vaginal mucosa suppository Code NBOG (Notified Body Operations Group): MD0303- CumLaude CLX ®

Eligibility Criteria

Exclusion Criteria

Patients with a history of previous preterm birth.

• Patients with vaginal bleeding during the first trimester.
• Patients with abnormalities detected in the first trimester ultrasound scan.
• Twin pregnancies
• Patients with a known allergy to the topical use of Chlorhexidine in any of its forms of presentation.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospital Universitario La Fe

OTHER

Sponsor Role: collaborator

Instituto de Investigacion Sanitaria La Fe

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José Morales-Roselló, Prof.Dr

Role: PRINCIPAL_INVESTIGATOR

Instituto de Investigación Sanitaria La Fe

Locations

Hospital Uiversitario y Politécnico La Fe

Valencia, , Spain

Countries

Spain

References

Brown RG, Marchesi JR, Lee YS, Smith A, Lehne B, Kindinger LM, Terzidou V, Holmes E, Nicholson JK, Bennett PR, MacIntyre DA. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med. 2018 Jan 24;16(1):9. doi: 10.1186/s12916-017-0999-x.

Reference Type: BACKGROUND

PMID: 29361936 (View on PubMed)

MacIntyre DA, Chandiramani M, Lee YS, Kindinger L, Smith A, Angelopoulos N, Lehne B, Arulkumaran S, Brown R, Teoh TG, Holmes E, Nicoholson JK, Marchesi JR, Bennett PR. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 2015 Mar 11;5:8988. doi: 10.1038/srep08988.

Reference Type: RESULT

PMID: 25758319 (View on PubMed)

Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Nikita L, Galuppi M, Lamont RF, Chaemsaithong P, Miranda J, Chaiworapongsa T, Ravel J. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014 Feb 3;2(1):4. doi: 10.1186/2049-2618-2-4.

Reference Type: RESULT

PMID: 24484853 (View on PubMed)

Spear GT, French AL, Gilbert D, Zariffard MR, Mirmonsef P, Sullivan TH, Spear WW, Landay A, Micci S, Lee BH, Hamaker BR. Human alpha-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J Infect Dis. 2014 Oct 1;210(7):1019-28. doi: 10.1093/infdis/jiu231. Epub 2014 Apr 15.

Reference Type: RESULT

PMID: 24737800 (View on PubMed)

Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007 Jun;21(3):375-90. doi: 10.1016/j.bpobgyn.2006.12.005. Epub 2007 Jan 22.

Reference Type: RESULT

PMID: 17241817 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

PLUVA

Identifier Type: -

Identifier Source: org_study_id