WILL (When to induce labour to limit risk in pregnancy hypertension): Protocol for a multicentre randomised trial

Abstract

Objectives: To address optimal timing of birth for women with chronic or gestational hypertension who reach term and remain well.

Study design: Pragmatic, non-masked randomised trial.

Inclusion: maternal age ≥16 years, chronic or gestational hypertension, singleton pregnancy, live fetus, 36⁺⁰-37⁺⁶ weeks' gestation, and able to give documented informed consent.

Exclusion: contraindication to either trial arm (e.g., pre-eclampsia or another indication for birth at term), blood pressure (BP) ≥ 160/110 mmHg until controlled, major fetal anomaly anticipated to require neonatal care unit admission, or participation in another timing of birth trial. Randomisation (1:1 ratio, minimised for key prognostic variables: site, hypertension type, and prior Caesarean) to 'planned early term birth at 38^+0-3 weeks' or 'usual care at term' (revised from 'expectant care until at least 40⁺⁰ weeks', Aug 2022).

Outcomes: Maternal co-primary: composite of 'poor maternal outcome' (severe hypertension, maternal death, or maternal morbidity). Neonatal co-primary: neonatal care unit admission for ≥4 h. Each co-primary is measured until primary hospital discharge or 28 days post-birth (whichever is earlier). Key secondary: Caesarean birth.

Analysis: Sample of 1080 participants (540/arm) will detect an 8% reduction in the maternal co-primary (90% power, superiority hypothesis), and give 94% power for a between-group non-inferiority margin of difference of 9% in the neonatal co-primary. Analysis will be by intention-to-treat. Ethics approval has been obtained (NHS Health Research Authority London Fulham Research Ethics Committee, 18/LO/2033).

Conclusions: The study will provide data for women to make informed choices about their care and allow health systems to plan services.

Keywords: Hypertension; Induction; Maternal outcomes; Perinatal outcomes; Pregnancy; Timing of birth.