Preterm BirthPLUVANCT05944094
Preterm Labor Prevention Using Vaginal Antiseptics Prior to 16 Weeks of Gestation
An observational study of Preterm Birth, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Preterm Birth
- What is being tested?
- Clorhexidine
- Type of treatment
- Medical device
- How many people
- 1,117 participants
- Where
- 1 siteSpain
- Study dates
- 1 Jun 2021to 16 Jun 2023
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Study population: The population was defined by all pregnant patients previously dated by crown-rump length, who attended the initial control or first trimester screening without evident risk of preterm birth at the time of consultation at the Hospital Universitari i Politécnic La Fe during the year 2021.
Who may be able to join
None listed.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Efficacy of Chlorhexidine Use During the First Trimester as a Regulator of Vaginal Microbiota in Reducing Preterm Birth
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.
Read more
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.
Read the 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
- Being tested
- Clorhexidine
- Keywords
- Preterm birth, chlorhexidine, primary prevention
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClorhexidineDevice
Also called Code GMDN (Global Medical Device Nomenclature): 47673 - Vaginal mucosa suppository Code NBOG (Notified Body Operations Group): MD0303- CumLaude CLX ®
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Device: Clorhexidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preterm birth
Vaginal delivery before 34 weeks
Measured: 9 months
Secondary outcomes (3)
Cervical shortening
Cervical shortening below 25 mm before 34 weeks
Measured: 9 months
Threatened preterm labor
presence of regular uterine contractions associated with cervical modifications (dilatation and/or shortening of the cervix) before 37 weeks
Measured: 9 months
Premature rupture of membranes
Premature rupture of membranes before 37 weeks
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2023
- Study start1 Jun 2021
- Primary completion20 Dec 2022
- Study completion16 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,117 participants (actual)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Instituto de Investigacion Sanitaria La Fe
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario La Fe
- Responsible party
- Sponsor
- Investigators
- José Morales-Roselló, Prof.Dr, Principal investigator, Instituto de Investigación Sanitaria La Fe
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05944094
- Sponsor's protocol ID
- PLUVA
- Acronym
- PLUVA
- Status last verified
- Jun 2023
- First submitted
- 5 Jul 2023
- Last updated
- 13 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 29361936MacIntyre 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.
PubMed 25758319Romero 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.
PubMed 24484853Spear 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.
PubMed 24737800Leitich 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.
PubMed 17241817
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Efficacy of Chlorhexidine Use During the First Trimester as a Regulator of Vaginal Microbiota in Reducing Preterm Birth
- ClinicalTrials.gov ID
- NCT05944094
- Acronym / sponsor ID
- PLUVA / PLUVA
- Conditions
- Preterm Birth
- Keywords
- Preterm birth, chlorhexidine, primary prevention
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,117 participants (actual)
- Lead sponsor
- Instituto de Investigacion Sanitaria La FeUniversity, hospital or other
- Collaborators
- Hospital Universitario La Fe
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 20 Dec 2022 (actual)
- Study completion
- 16 Jun 2023 (actual)
- First posted
- 13 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Group 1: exposed patients | – | Device: ClorhexidineGroup 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 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- The population was defined by all pregnant patients previously dated by crown-rump length, who attended the initial control or first trimester screening without evident risk of preterm birth at the time of consultation at the Hospital Universitari i Politécnic La Fe during the year 2021.
Key inclusion criteria (0 listed)
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ClorhexidineAlso: Code GMDN (Global Medical Device Nomenclature): 47673 - Vaginal mucosa suppository Code NBOG (Notified Body Operations Group): MD0303- CumLaude CLX ®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. | Device | Group 1: exposed patients |
Primary outcome
Preterm birth
Time frame: 9 months
Vaginal delivery before 34 weeks
3 secondary outcomes
Cervical shortening
Time frame: 9 months
Threatened preterm labor
Time frame: 9 months
Premature rupture of membranes
Time frame: 9 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2023.
- Background: PubMed 29361936Brown 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.
- Results publication: PubMed 25758319MacIntyre 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.
- Results publication: PubMed 24484853Romero 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.
- Results publication: PubMed 24737800Spear 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.
- Results publication: PubMed 17241817Leitich 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José Morales-Roselló, Prof.Dr principal investigator
Instituto de Investigación Sanitaria La Fe
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preterm Birth, run by Instituto de Investigacion Sanitaria La Fe at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preterm birth (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05944094, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2023.