Prevention of Recurrent Spontaneous Preterm Delivery Using Probiotics (Clostridium butyricum, Enterococcus faecium, and Bacillus subtilis; PPP Trial): Protocol for a Prospective, Single-Arm, Nonblinded, Multicenter Trial (Preprint)

Author:

Yoneda SatoshiORCID,Kobayashi TohruORCID,Kikuchi KayokoORCID,Iwamoto ShintaroORCID,Teramoto TsuyoshiORCID,Chujo DaisukeORCID,Otsuki KatsufumiORCID,Nakai AkihitoORCID,Saito ShigeruORCID

Abstract

BACKGROUND

The rate of recurrent spontaneous preterm delivery (sPTD) ranges between 27% and 34% and is 22.3% in Japan. Although it currently remains unclear whether probiotics prevent sPTD, retrospective studies recently reported a reduction in the rate of recurrent sPTD with the administration of probiotics including <i>Clostridium</i> spp., which induce regulatory T cells that play an important role in maintaining pregnancy.

OBJECTIVE

The objective of this trial is to evaluate the preventative effects of available oral probiotics, including <i>Clostridium butyricum</i>, on recurrent sPTD.

METHODS

This is a prospective, single-arm, nonblinded, multicenter trial in Japan. The sample size required for this trial is 345 pregnant women with a history of sPTD, considering a clinically significant reduction in the relative risk of 30% (risk ratio=0.7). The primary endpoint is the rate of recurrent sPTD at &lt;37 weeks of gestation. The secondary endpoints are the rate of sPTD at &lt;34 weeks of gestation, the rate of recurrent sPTD at &lt;28 weeks of gestation, the ratio of intestinal <i>Clostridium</i> spp. (detected by next-generation sequencing), and bacterial vaginosis (using the Nugent score).

RESULTS

The trial procedures were approved by the Clinical Research Review Board of Toyama University Hospital (SCR2020008) on March 31, 2021. The trial was registered on the Japan Registry of Clinical Trial website on April 28, 2021. Recruitment began on May 1, 2021, and the trial is estimated to finish on March 31, 2025.

CONCLUSIONS

The findings will clarify the rate of recurrent sPTD following probiotic administration including <i>Clostridium butyricum</i>. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials.

CLINICALTRIAL

Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014

INTERNATIONAL REGISTERED REPORT

DERR1-10.2196/59928

Publisher

JMIR Publications Inc.

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