CaPE - Information for participants

Pre-eclampsia affects around 3% of pregnant women in the UK. Complications linked to pre-eclampsia are a major cause of poor outcomes for mothers and their babies. We are investigating whether taking calcium supplements throughout pregnancy can help prevent pre-eclampsia.

The main symptoms of pre-eclampsia are raised blood pressure and protein in the mother’s urine – things that midwives check at every antenatal appointment. Pre-eclampsia develops in the second half of pregnancy, and get worse very quickly in some women. We still don’t really understand what causes pre-eclampsia and the only cure is to deliver the baby. 

Women who have a history of pre-eclampsia, or certain risk factors and other health conditions are more likely to develop pre-eclampsia during their pregnancy. They are usually offered a small daily dose of aspirin by the NHS as this can help to reduce cases. Research in other countries has found that taking regular doses of calcium can also help. However, women in those countries often have diets which are low in calcium, whereas women in the UK generally eat foods with plenty of calcium.

The CaPE trial wants to find out if calcium is a useful supplement for preventing pre-eclampsia in the UK in women who have a high risk of developing pre-eclampsia. If our research shows that calcium helps prevent pre-eclampsia, it will be added to the national guidance written for doctors and midwives caring for women during pregnancy. 

CaPE is a randomised controlled trial. This means that the pregnant women who agree to take part will be randomly assigned by a computer to take either a calcium supplement or a placebo – a tablet which looks identical to the calcium supplement but doesn’t contain any.

The women and their midwives and doctors will not know whether they are taking the calcium or the placebo, and they can’t express a preference for one or the other. Also, the researchers doing the study will not know which group of women has taken the supplement or the placebo.

We plan to recruit 7756 pregnant women from hospitals across the UK.

Part of our project is assessing the costs and benefits for the NHS of giving calcium supplements.

The technical term for the type of research we are conducting is a parallel-two-arm, randomised, triple-blinded, placebo-controlled multi-centre trial, with a 12-month internal pilot and health economics evaluation.

To compare the effectiveness of calcium supplements plus standard antenatal care with standard care alone, for the prevention of pre-eclampsia and its complications in women at high risk of pre-eclampsia. 

We will recruit pregnant women from approximately 40 NHS hospitals providing maternity care across the UK.

Intervention group

The women randomised to the take calcium tablets will be asked to take 2 grams per day starting between 12 and 22 weeks' of pregnancy and continuing until birth. They will receive all the normal NHS antenatal care, including aspirin tablets.

Control group

The women randomised to take the placebo will be asked to take the dummy tablets starting between 12 and 22 weeks' of pregnancy and continuing until birth. They will receive all the normal NHS antenatal care, including aspirin tablets.

Primary Objective

To test the hypothesis that in pregnant women at increased risk of pre-eclampsia, calcium supplementation given in a dose of 2 grams per day during pregnancy plus usual care (including aspirin) is more effective than usual care alone in reducing the relative risk for the occurrence of pre-eclampsia by at least 20%.

Secondary Objectives

1. To assess the impact of calcium supplements on other important outcomes for the mother and baby.
2. To assess the cost-effectiveness of calcium plus usual care compared to usual care alone.
3. To assess the degree to which pregnant women are able to adhere to calcium supplementation regimen.
4. To assess whether calcium has a differential effect in pre-specified subgroups of women.

Clinician diagnosis of pre-eclampsia, based on the ISSHP definition: a blood pressure ≥140/90mmHg AND either:

1.      Significant proteinuria (protein/creatinine ratio (PCR) of 30 mg/mmol or more) OR

2.      Maternal multiorgan dysfunction:

a.      Acute kidney injury (AKI) (creatinine ≥90 μmol/L)

b.      Liver involvement (elevated transaminases e.g. alanine transaminase (ALT) or aspartate transaminase (AST) >40IU/L) with or without right upper quadrant or epigastric abdominal pain)

c.       Neurological complications (including eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, persistent visual scotomata)

d.      Haematological complications (thrombocytopenia – platelet count below 150,000/μL, DIC, haemolysis) OR

3.      Uteroplacental insufficiency (fetal growth restriction, abnormal Umbilical artery doppler, stillbirth)

 developing at or after 20 weeks gestation.

Secondary outcomes

• For the woman: death, eclampsia, stroke, HELLP syndrome, cortical blindness, pulmonary oedema, acute kidney injury, liver capsule haematoma, abruption, postpartum haemorrhage, ITU admission, intubation, mechanical ventilation, gestational and severe hypertension, early onset pre-eclampsia <34 weeks, need for elective delivery, mode of delivery, composite morbidity, adverse effects.
• For the baby: death before hospital discharge, gestational age at delivery, birthweight, small for gestational age, admission to neonatal unit and level of care, number of admission days, neonatal brain injury syndromes, respiratory support, preterm birth <34 and <37 weeks, chronic lung disease, necrotising enterocolitis, intraventricular haemorrhage, retinopathy of prematurity, and composite neonatal morbidity/mortality.
• Adherence to calcium.
• Health economics analyses.

Funder: National Institute of Health Research (HTA programme ref. NIHR 127325)

Sponsor: University of Birmingham (ref. RG_20-128)

EudraCT number: 2020-004435-25

ISRCTN number: ISRCTN 12033893

Chief Investigator: Dr Shireen Meher

 This study is funded by the National Institute for Health Research (NIHR) [HTA programme (NIHR 127325)]. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.