WILL

When to Induce Labour to Limit risk in pregnancy hypertension - a multicentre, randomised controlled trial

Sponsored by King’s College London and Guy’s & St Thomas’ NHS Foundation Trust


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***Important Message: COVID-19***

We are now home-based during the COVID-19 pandemic but available and working. Responses may however take longer than normal as staff may be working altered hours but we are cross covering trials as required and urgent matters will be dealt with promptly. Please do not contact our usual office/landline number and instead email Katie Kirkham  - K.L.Kirkham@bham.ac.uk - and copy in will@trials.bham.ac.uk. If a query requires a prompt response please mark as ‘urgent’ in the email subject header

Aim

To investigate the clinical effectiveness and cost-consequences of planned early term delivery at 38+0 to 38+3 weeks’ gestation, compared with expectant care at term until at least 40+0 weeks’ gestation, in pregnant women with chronic or gestational hypertension that develops by 37+6 weeks’ gestation.

Design

A pragmatic, parallel-group, open-label, multicentre, randomised controlled trial (with an internal pilot) with two co-primary outcomes: a maternal outcome assessing superiority and a neonatal outcome assessing non-inferiority.

Intervention

Planned early term delivery at 38+0 to 38+3 weeks by labour induction (local protocol) or elective Caesarean (if previously indicated).

Expectant care at term until at least 40+0 weeks, with maternal and fetal monitoring (local protocol), awaiting spontaneous labour or delivery indicated by clinical need (e.g., refractory severe hypertension or pre-eclampsia).

Eligibility criteria

INCLUSION CRITERIA:
  1. Maternal age ≥16 years;
  2. Diagnosis of chronic or gestational hypertension (see protocol Section 4.1);
  3. Singleton pregnancy;
  4. Live fetus;
  5. Gestational age of 36+0 to 37+6 weeks; and
  6. Able to give written informed consent to participate.

EXCLUSION CRITERIA:

  1. Contraindication to either one of the trial arms (e.g. evidence of pre-eclampsia);
  2. Severe hypertension [i.e., blood pressure (BP) ≥160mmHg systolic or ≥110mmHg diastolic] until BP falls below this level (i.e. it is ‘controlled’, see protocol Section 4.2);
  3. Major fetal anomaly anticipated to require neonatal unit admission; or
  4. Participation in another timing of delivery trial.
NOTE:   Neither maternal co-morbidities (e.g., diabetes) nor fetal size will be exclusion criteria.

Outcomes

Primary Outcome Measures:

mother: Composite of poor maternal outcome until primary hospital discharge home or 28 days after birth (whichever is earlier), defined as:

• Severe hypertension (i.e., systolic BP (sBP) ≥160 or diastolic BP ≥110mmHg); or

• Maternal death; or

• Maternal morbidity defined as any of the following: GCS<13; stroke; TIA; eclampsia; blindness; uncontrolled hypertension; inotropic support; pulmonary oedema; respiratory failure; SpO2 <90%; myocardial ischaemia or infarction; hepatic dysfunction, hepatic haematoma or rupture; acute kidney injury or dialysis; platelet count <50x109/L; transfusion; or placental abruption. These were adapted from a Delphi consensus in hypertensive pregnancy(10;11).

baby: Neonatal care unit admission for ≥ 4 hours, until primary hospital discharge home or 28 days after birth (whichever is earlier).

Secondary Outcome Measures (assessed at hospital discharge or 28 days postpartum, whichever is earlier, unless otherwise stated):

Maternal

  • Caesarean delivery
  • Instrumental vaginal delivery or Caesarean delivery (vs. spontaneous vaginal delivery)
  • Infection of the Caesarean wound, episiotomy, or vaginal tear, as applicable, assessed at six weeks postpartum
  • Individual components of poor maternal outcome
  • ‘Poor maternal outcome’ assessed at six weeks postpartum
  • Elevated liver enzymes
  • Platelet count <100x109/L
  • Pre-eclampsia
  • Sepsis
  • Postpartum haemorrhage (PPH)
  • Intensive therapy unit (ITU) admission
  • Potential co-interventions, including antihypertensive therapy taken; magnesium sulphate; bedrest at home; use of home BP monitoring; maternal blood or urine testing at the laboratory prior to delivery admission; outpatient visits; medical, day, or maternity assessment unit visits; acute care visits; antenatal admissions; fetal cardiotocography; and fetal ultrasound
  • Clinical indications for delivery in the expectant care arm
  • Maternal satisfaction, as measured by the Childbirth Experience Questionnaire 2.0

Neonatal

  • Neonatal care unit admission
  • Indication for neonatal care unit admission ≥ 4 hours
  • Respiratory morbidity
  • Hypoxic-ischaemic encephalopathy (HIE)
  • Sepsis
  • Major operation
  • Birthweight
  • Apgar scores at 1, 5 and 10 minutes
  • Stillbirth
  • Neonatal death
  • Breastfeeding established
  • Exclusive breastfeeding

Health Economics

  • Cost-consequence analysis from NHS perspective (enrolment to hospital discharge)

Setting and target population

The trial will recruit 1,080 pregnant women with chronic or gestational hypertension, from NHS consultant-led maternity units in the UK.