TY  - JOUR
AU  - Yoneda, Satoshi
AU  - Kobayashi, Tohru
AU  - Kikuchi, Kayoko
AU  - Iwamoto, Shintaro
AU  - Teramoto, Tsuyoshi
AU  - Chujo, Daisuke
AU  - Otsuki, Katsufumi
AU  - Nakai, Akihito
AU  - Saito, Shigeru
PY  - 2024
DA  - 2024/9/9
TI  - 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
JO  - JMIR Res Protoc
SP  - e59928
VL  - 13
KW  - clostridium
KW  - multicenter open label trial
KW  - preterm delivery
KW  - probiotics
KW  - recurrent spontaneous preterm delivery
KW  - prospective single-arm
KW  - spontaneous preterm delivery
KW  - infection
KW  - oral probiotics
KW  - pregnant women
KW  - pregnant
KW  - pregnancy
KW  - neonates
KW  - preterm births
KW  - systematic review
KW  - meta-analysis
AB  - 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 Clostridium 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 Clostridium butyricum, 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 <37 weeks of gestation. The secondary endpoints are the rate of sPTD at <34 weeks of gestation, the rate of recurrent sPTD at <28 weeks of gestation, the ratio of intestinal Clostridium 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 Clostridium butyricum. Outcomes from this trial will inform clinical practice and guide future randomized controlled trials. Trial Registration: Japan Registry of Clinical Trials jRCTs041210014; https://jrct.niph.go.jp/latest-detail/jRCTs041210014 International Registered Report Identifier (IRRID): DERR1-10.2196/59928 
SN  - 1929-0748
UR  - https://www.researchprotocols.org/2024/1/e59928
UR  - https://doi.org/10.2196/59928
DO  - 10.2196/59928
ID  - info:doi/10.2196/59928
ER  -