Screening for Bacterial Vaginosis to Prevent Premature Birth

(SECRETIVA Trial)

Overseen By Ashra Denise Tugung, BSc

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Loma Linda University

Disqualifiers: Multigestation, Preeclampsia, Cervical dilation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: 18 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of this investigator-initiated randomized control trial is to determine if bacterial vaginosis infection increases the likelihood of preterm delivery in women with history of preterm delivery. Subjects will be randomized in a two-arm study to undergo predetermined intervals of testing for bacterial vaginosis or control.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is the treatment for bacterial vaginosis safe for humans?

Metronidazole, used in various forms like oral tablets and vaginal gels, has been studied for safety in treating bacterial vaginosis. It is generally considered safe, but in some cases, it may increase the risk of preterm birth when used for other infections like trichomoniasis during pregnancy. ^{1 2 3 4 5}

How does the drug used in the trial for preventing premature birth differ from other treatments for bacterial vaginosis?

The drug used in the trial is metronidazole, which is unique because it can be administered as a single-dose vaginal gel, offering a more convenient option compared to the traditional once or twice daily regimens over several days. ^{3 4 6 7 8}

What data supports the effectiveness of the drug metronidazole in preventing premature birth in pregnant women with bacterial vaginosis?

Research shows that treating bacterial vaginosis with metronidazole does not prevent preterm birth and may even increase the risk in some cases, such as with trichomoniasis. However, metronidazole gel was found to be effective in treating bacterial vaginosis, which is a risk factor for preterm birth, suggesting it might help in some cases. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for pregnant women over 18, less than 32 weeks along, with a history of early delivery or short cervix. They must get care at Loma Linda and follow the study plan. It's not for those with certain conditions like severe preeclampsia or who aren't at high risk for early birth.

Inclusion Criteria

History of at least one prior preterm delivery >16 and <37 weeks not due to iatrogenic indications, or short cervical length <2.5cm

I am female.

Pregnancy at less than 32 weeks gestational age at initial obstetric visit with Loma Linda Maternal Fetal Medicine (MFM) Clinic

Exclusion Criteria

I want to end my current pregnancy.

Current pregnancy is multigestation

Patients not deemed to be high risk for preterm delivery

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants in the intervention arm undergo vaginal swab collections every 2 weeks from 16 to 34 weeks gestational age

18 weeks

9 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Postpartum Monitoring

Monitoring of mothers and neonates for length of hospital stay

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Additional vaginal swabs

Trial Overview The study tests if extra vaginal swabs to screen for bacterial vaginosis can prevent preterm births in women with a history of it. Participants are randomly placed into two groups: one gets regular testing and treatment; the other follows standard prenatal care.

How Is the Trial Designed?

Group I: Intervention Arm Active Control 1 Intervention

The intervention-arm will have a pelvic exam performed with vaginal swab collection at their initial obstetric visit (standard of care). The women undergoing the intervention will then subsequently undergo additional vaginal swab collections in 2 week intervals starting at 16 weeks gestational age until 34 weeks gestational age. Subjects will be informed of the results of the vaginal swab. If positive for an infection, subjects will be provided with the appropriate treatment in pregnancy.

Group II: Control Arm Active Control 1 Intervention

The control arm will undergo the standard of care with vaginal swab collection at their initial obstetric visit. The control arm will not undergo additional vaginal swab collections unless otherwise indicated under standard of care (further testing for bacterial vaginosis is completed in women who describe symptoms with the diagnosis or present for preterm contractions and/or pelvic cramping). There will be no placebo for the control group.

Who Is Running the Clinical Trial?

Loma Linda University

Lead Sponsor

Trials

322

Recruited

267,000+

Published Research Related to This Trial

In a randomized controlled trial of 126 pregnant women with bacterial vaginosis (BV), both oral and vaginal metronidazole treatments significantly reduced BV-associated bacteria, but only 34% achieved a therapeutic cure, indicating limited effectiveness in restoring a healthy vaginal environment.

While treatment led to a significant decrease in the proinflammatory cytokine IL-1beta and an increase in secretory leukocyte protease inhibitor (SLPI) among those who achieved a cure, neither treatment method effectively restored protective lactobacilli, which are important for vaginal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy. Mitchell, C., Balkus, J., Agnew, K., et al.[2021]

In a study involving 1,005 pregnant women, metronidazole treatment for bacterial vaginosis did not significantly reduce the rates of preterm labor compared to those who received vitamin C or had no bacterial vaginosis.

Women treated with metronidazole had lower birth weights and higher rates of preterm delivery compared to those without bacterial vaginosis, indicating that metronidazole may not be an effective intervention for preventing preterm labor in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preterm labour--is bacterial vaginosis involved? Odendaal, HJ., Popov, I., Schoeman, J., et al.[2014]

In a study of 200 pregnant women, 38.5% of those with vaginal discharge were found to have Bacterial Vaginosis (BV), highlighting its prevalence as a risk factor during pregnancy.

Treatment with intravaginal metronidazole gel was effective in managing BV, and untreated cases showed a higher incidence of preterm labor, suggesting the importance of treating BV to improve pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of bacterial vaginosis in antenatal women. Mathew, R., Kalyani, J., Bibi, R., et al.[2013]

Two large randomized clinical trials involving asymptomatic pregnant women with bacterial vaginosis or trichomoniasis found that metronidazole treatment did not prevent preterm birth in women with bacterial vaginosis.

In fact, treating women with trichomoniasis with metronidazole increased the risk of preterm birth compared to those receiving a placebo, leading to recommendations against screening for bacterial vaginosis in low-risk pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What have we learned about vaginal infections and preterm birth? Carey, JC., Klebanoff, MA.[2019]

In a study of 80 pregnant women with a history of preterm birth, treatment with metronidazole for bacterial vaginosis significantly reduced the rates of preterm labor and preterm births compared to a placebo group.

Patients treated with metronidazole had fewer hospital admissions for preterm labor (27% vs. 78%), fewer preterm births (18% vs. 39%), and lower rates of infants born weighing less than 2500 grams, indicating that metronidazole is an effective intervention for this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. Morales, WJ., Schorr, S., Albritton, J.[2019]

In a study involving 196 pregnant women with bacterial vaginosis, short courses of oral metronidazole significantly suppressed bacterial vaginosis for up to 4 weeks in 76% of participants, compared to only 28% in the placebo group.

Metronidazole therapy showed a cumulative efficacy of 87% after two courses, indicating that it can effectively manage bacterial vaginosis in pregnancy, which is important since this condition is linked to an increased risk of preterm labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial. McDonald, HM., O'Loughlin, JA., Vigneswaran, R., et al.[2013]

In a phase 3 study involving 651 women, single-dose metronidazole vaginal gel (MVG) 1.3% was found to be significantly more effective than a vehicle gel, achieving higher clinical and therapeutic cure rates at day 21 (37.2% vs. 26.6% and 16.8% vs. 7.2%, respectively).

MVG 1.3% also led to quicker symptom resolution, with a median time to resolution of 6 days compared to the vehicle group, and it was shown to be safe with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis. Schwebke, JR., Marrazzo, J., Beelen, AP., et al.[2022]

Intravaginal metronidazole is highly effective for treating bacterial vaginosis, with a cure rate of 78% compared to only 27% for placebo, and 91% of those initially cured remained free of symptoms one month later.

The treatment is safe and well-tolerated, with only mild side effects reported, and the Gram stain score may help predict which patients are at risk for recurrence after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bacterial vaginosis: efficacy and safety of intravaginal metronidazole treatment. Livengood, CH., McGregor, JA., Soper, DE., et al.[2019]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Changes in the vaginal microenvironment with metronidazole treatment for bacterial vaginosis in early pregnancy. [2021]

2. South Africa pubmed.ncbi.nlm.nih.gov

Preterm labour--is bacterial vaginosis involved? [2014]

3. India pubmed.ncbi.nlm.nih.gov

Prevalence of bacterial vaginosis in antenatal women. [2013]

4. United States pubmed.ncbi.nlm.nih.gov

What have we learned about vaginal infections and preterm birth? [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of metronidazole in patients with preterm birth in preceding pregnancy and bacterial vaginosis: a placebo-controlled, double-blind study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Bacterial vaginosis in pregnancy and efficacy of short-course oral metronidazole treatment: a randomized controlled trial. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

A Phase 3, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Study Evaluating the Safety and Efficacy of Metronidazole Vaginal Gel 1.3% in the Treatment of Bacterial Vaginosis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Bacterial vaginosis: efficacy and safety of intravaginal metronidazole treatment. [2019]