Prevention of pre-eclampsia in women at increased risk Pregnancy and Childbirth Pre-eclampsia
Conditions
Interventions
Pregnant women who meet the eligibility criteria of the trial will be randomised using a minimisation algorithm to ensure balance in treatment allocation (central randomisation, 1:1 ratio, with minimi
Sponsors
University of Birmingham
Eligibility
Sex/Gender
Female
Age
16 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. Over 16 years of age 2. Able to provide informed consent to participate 3. After a dating scan has confirmed viability (usually between 10 and 14 weeks gestation) 4. 22 weeks’ 0 days gestation or less 5. Women deemed eligible for aspirin therapy based on NICE guideline criteria below where a woman has either: 5.1. One high-risk factor: 5.1.1. Hypertensive disease during a previous pregnancy 5.1.2. Chronic renal disease 5.1.3. Autoimmune disease such as SLE or antiphospholipid syndrome 5.1.4. Type 1 or 2 diabetes 5.1.5. Chronic hypertension 5.2. Or two or more moderate risk factors: 5.2.1. First pregnancy 5.2.2. Age more than 40 years 5.2.3. BMI =35 at first visit 5.2.4. Family history of pre-eclampsia 5.2.5. Multiple pregnancy 5.2.6. Pregnancy interval of 10 years or more 5.3. Or the Fetal Medicine Foundation (FMF) algorithm for pre-eclampsia risk assessment, as used locally 5.4. Or any other national pre-eclampsia screening criteria guidelines that may be used in the future The study will also include women identified to be at high risk of pre-eclampsia based on any other national screening criteria guidelines that may be used in the future.
Exclusion criteria
Exclusion criteria: 1. Any known contraindications to regular calcium intake (history of renal stones, known renal impairment with pre-pregnancy eGFR 150 (µmol/l), known history of hypercalcaemia or hypercalcaemia-causing diseases (e.g. parathyroid disease, sarcoidosis, malignancy), current severe persistent vomiting leading to dehydration or requiring hospitalisation (if persisting vomiting resolves, the patient may be re-assessed for inclusion in the trial, providing all other inclusion and exclusion criteria are met) 2. Use of drugs with potential for severe interactions with calcium: digoxin or other cardiac glycosides; antiretroviral drugs for HIV treatment, anti-neoplastic drugs, and diuretics (thiazide, thiazide-like or xipamide). 3. Use of any additional calcium supplement either on its own or as part of other multivitamin or Vitamin D preparations, and unwilling to stop them or change to other multivitamins, as this could lead to higher doses of calcium supplementation in the calcium group and contamination in the placebo group 4. Women who are taking vitamin D regularly in high doses >1000 IU/day, as supplements or for conditions such as malabsorption syndromes. Note: a short course of high dose Vitamin D (e.g., 20,000 IU weekly for 6 weeks) to treat Vitamin D deficiency during pregnancy is NOT an exclusion criteria 5. Known contraindications to excipient Isomalt (e.g. hereditary fructose intolerance)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pre-eclampsia, as defined by the International Society for the Study of Hypertension in Pregnancy (ISSHP), assessed up to primary hospital discharge after birth | — |
Secondary
| Measure | Time frame |
|---|---|
| All secondary outcomes will be measured using patient medical records up to hospital discharge or 4 weeks after estimated delivery, whichever is sooner. For the woman: Pre-eclampsia Core Outcome Set (COS) outcomes, namely: 1. Death 2. Eclampsia 3. Stroke 4. Visual impairment: retinal detachment or cortical blindness 5. Pulmonary oedema 6. Acute kidney injury: creatinine =90 µmol/l; 1 mg/dl 7. Liver capsule haematoma (confirmed on ultrasound) 8. Raised liver enzymes: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >40 IU/l 9. Low platelets 1.1 mg/dl), or pulmonary edema or visual impairment or severe headache unresponsive to medication and no other cause found. 17. HELLP syndrome based on a clinician diagnosis, supported by low platelets and raised liver enzymes as defined above with or without evidence of haemolysis (raised LDH enzyme or blood film) 18. Preterm pre-eclampsia: 18.1. Diagnosed before 37 weeks 18.2. Diagnosed before 32 weeks 19. Use of magnesium sulphate for pre-eclampsia 20. Onset of birth: spontaneous, induction of labour or elective Caesarean section 21. Mode of birth: vaginal birth, assisted vaginal birth, Caesarean section (emergency or elective) 22. Adverse effects: maternal hypercalcaemia, renal stones, neonatal hypocalcaemia, stopping of medication due to adverse effects For the baby: COS outcomes namely: 1. Any death in the baby up to hospital discharge. The researchers will collect data separately for: 1.1. Fetal loss <22 weeks gestation 1.2. Fetal loss =22 weeks’ gestation (stillbirth) 1.3. Neonatal death (from birth up to 28 days) 1.3.1. Early neonatal death (up to 7 days after birth) 1.3.2. Late neonatal death (from 7 days up to 28 days) 1.4. Perinatal death – stillbirth or neonatal death up to 7 days 2. Gestational age at delivery (median, <28 weeks, <32 weeks, <37 weeks) 3. Birthweight (mean, <3rd centile, <10th centile) 4. Admission to NNU 4.1. Any admission 4.2. Days of admission 5. Neonatal brain inj | — |
Countries
England, United Kingdom
Contacts
Public ContactMax Hughes
Outcome results
None listed