Recombinant human relaxin versus placebo for cervical ripening: a double-blind randomised trial in pregnant women scheduled for induction of labour

Gerson Weiss, Sam Teichman, Dennis Stewart, David Nader, Susan Wood, Peter Breining, Elaine Unemori, Gerson Weiss, Sam Teichman, Dennis Stewart, David Nader, Susan Wood, Peter Breining, Elaine Unemori

Abstract

Background: Nonclinical studies indicate that the hormone relaxin is a good candidate for a safe cervical ripening agent that does not cause uterine contractions.

Methods: This Phase II study (conducted November 2, 2005-October 20, 2006) was a randomised, double blind, placebo controlled trial testing 24-h intravenous infusion of serelaxin (recombinant human relaxin) or placebo for cervical ripening in 72 healthy, primiparous women. Eligible subjects had a singleton pregnancy ≥40 weeks, were planned for elective induction, had vertex presentation of the fetus, intact membranes and a Bishop score at screening ≤4. In Part A of the study, safety evaluation of three escalating doses of serelaxin (7.5, 25 or 75 μg/kg/day) or placebo was performed in 22 subjects admitted to the hospital 24 h prior to scheduled induction (n = 7, 4, 4, and 7 subjects, respectively). The highest safe dose from Part A and placebo were then tested in Part B for safety and cervical ripening (n = 25 subjects/arm). Planned randomisation ratio was of 4:2 (serelaxin:placebo) for each dose group in Part A and 1:1 for Part B. For analysis, subjects in Part B were pooled with those receiving the same dose in Part A and all subjects receiving placebo were pooled. The primary efficacy endpoint was change from baseline in Bishop score at 6, 12 and 24 h or end of study drug administration. Maternal safety evaluations included adverse events and vital signs through 4 weeks. Fetal assessments included serial heart rate monitoring and nonstress testing. Neonatal assessments included Apgar scores, NICU admissions, and adverse events through 4 weeks.

Results: Overall, 74 subjects were randomized and 72 were treated. There were no significant differences between the groups receiving the highest safe dose of serelaxin (75 μg/kg/day) and placebo in the primary or secondary efficacy endpoints. Changes from baseline in Bishop score at 24 h were 4.19 ± 1.9 and 3.26 ± 2.26 in the pooled placebo and serelaxin groups, respectively (p = 0.2507). Serelaxin was well tolerated and no anti-serelaxin antibodies were detected in either subjects or neonates.

Conclusion: Serelaxin infusion at the end of pregnancy was well tolerated but did not advance cervical ripening.

Trial registration: Clinicaltrials.gov identifier NCT00259103 (15 November 2005).

Keywords: Cervical ripening; Relaxin; Serelaxin.

Figures

Fig. 1
Fig. 1
Trial profile (CONSORT 2010). PP Per protocol (received ≥18 h of study drug infusion). *All subjects were treated as allocated
Fig. 2
Fig. 2
Plasma concentrations of relaxin and serelaxin. Plasma levels of relaxin + serelaxin (mean ± SEM), measured at baseline (0) and at 6, 12, and 24 h from the start of study drug administration in primiparous women ≥40 weeks of pregnancy in the pooled placebo and pooled MTD serelaxin groups. In the placebo group, only endogenous relaxin-2 is measured, while in the pooled MTD group, both serelaxin and endogenous relaxin-2 are detected

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