Novel oxytocin receptor antagonists for tocolysis: a systematic review and meta-analysis of the available data on the efficacy, safety, and tolerability of retosiban

Abstract

Objective

To assess the efficacy, safety, and tolerability of retosiban—a novel tocolytic unavailable in the US—in the management of preterm labor.

Methods

We searched ClinicalTrials.Gov, MEDLINE, PubMed, SCOPUS, Web of Science, and the Cochrane Library for relevant clinical trials using the terms “retosiban” and “preterm labor” through 09/2020. We included all published randomized clinical trials (three) that compared retosiban to placebo for preterm labor, excluding conferences, books, reviews, posters, case reports, and animal studies. We analyzed homogeneous data under the fixed-effects model and heterogeneous data under the random-effects model.

Results

We included all randomized clinical trials addressing this topic, which ultimately resulted in three trials with a total of 116 patients. There were no significant differences between retosiban and placebo in births at term (RR = 0.41, p = .02), births ≤7 days from the first study treatment (RR = 0.59, p = .23), or administration of rescue tocolytic (RR = 0.36, p = .07); the maternal adverse events of headache, anemia, constipation, or urinary tract infection (p > .05); or neonatal outcomes of Apgar score at 1 min (p = .88) or 5 min (p = .69), weight (p = .23), head circumference (p = .55), malnutrition (p = .27), hyperbilirubinemia (RR = 0.56, p = .21), jaundice (RR = 1.21, p = .84), respiratory distress (RR = 0.53, p = .49), or tachypnea (RR = 0.40, p = .42).

Conclusion

With the limited high quality evidence available, retosiban demonstrates no clear benefit over placebo in the management of preterm labor. Nevertheless, its favorable safety profile, oral bioavailability, and novel mechanism of action and the limited number of studies available for review warrant further analysis.

Keywords:

• Novel medication
• preterm birth
• preterm labor
• retosiban
• systematic review
• tocolytic

Transparency

Declaration of funding

All authors deny receiving compensation of any kind related to this research, collectively or individually.

Declaration of financial/other relationships

All authors deny financial or other relationships of any kind that are pertinent to this research, collectively or individually. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

GM and RB were responsible for the concepts, resources, software, study design, and supervision of this work. KW, JV, AK, and SR conducted the systematic review and data analysis. GB, KC, NC, and HU drafted the initial form of the article. KW, SR, and KS designed the tables and figures. AR performed critical edits to the manuscript, tables and figures and finalized the content. All authors attest to significant contributions and agree to be accountable for all aspects of this work.

Acknowledgements

The Marchand Institute for Minimally Invasive Surgery would like to acknowledge the efforts of all of the students, researchers, residents and fellows at the institute who put their time and effort into these projects without compensation, only for the betterment of medicine. We firmly assure them that the future of medicine belongs to them.

Data availability statement

There are no data sets affiliated with this systematic review article.