The vaginal microbiota is a determinant for the risk of preterm birth (PTB). Dominance of the vaginal niche by Lactobacillus crispatus associates with term delivery. Vaginal administration of Lactobacillus crispatus as a live biotherapeutic in non-pregnant women leads to colonisation and reduced recurrence of bacterial vaginosis and urinary tract infections. This is a first in-pregnancy observational clinical study of live vaginal biotherapeutics (Lactobacillus crispatus CTV-05 (LACTIN-V, Osel)) in a cohort of pregnant women at high-risk of PTB. The primary aim was to explore safety, tolerability and acceptability of LACTIN-V in pregnancy.
Pregnant women at high-risk of PTB were offered a course of LACTIN-V at 14 weeks gestation for 5 consecutive days followed by weekly administration for 6 weeks. Participants were followed up at 15, 18-, 20-, 28- and 36-weeks’ gestation and at delivery for assessment of adverse events, compliance, and tolerance. After study completion, women completed a questionnaire to gauge experience and acceptability. Assessment of adverse events was performed in those women completing LACTIN-V therapy and those who commenced LACTIN-V but later withdrew from the study.
A total of 73 women were recruited, of whom 8 withdrew, leaving a final cohort size of 61. Overall patient reported compliance to the full course was high (56/60, 93%). Solicited adverse events were reported in 13 women (19%) including changes in vaginal discharge, odour, colour or consistency of urine, itching and vaginal bleeding. One unsolicited adverse event was reported as haematuria at 38 weeks gestation, but was not judged to be related to LACTIN-V and no serious adverse events occurred. One mild adverse event led to withdrawal from the study. A total of 31 women completed an experience and acceptability questionnaire. Women found LACTIN-V easy and comfortable to use and the majority (30/31, 97%) stated they would use LACTIN-V in future pregnancies. Eight women (8/31, 26%) reported that the schedule of use was difficult to remember. The rate of early PTB <34 weeks in this cohort was 3.3% compared to 7% in a historical cohort of 2190 women at similar background PTB risk.
With satisfactory uptake and good compliance, we demonstrate that LACTIN-V is safe and well accepted in pregnancy, with high tolerability. Further studies are needed to assess rates of Lactobacillus crispatus CTV-05 colonisation and clinical efficacy.
The trial is registered at www.clinicaltrials.gov (NCT03992534). Date of registration was June 20, 2019