New randomized trials
Aspirin versus placebo in twin pregnancies for preeclampsia prevention: A multicentre, randomised, double-blind, placebo-controlled trial (ASPRE-T)
This is a double-blind randomised placebo-controlled multicentre trial. In the participating centres, all eligible women with dichorionic and monochorionic-diamniotic twin pregnancies attending for their routine first hospital visit in pregnancy at 11-13 weeks’ gestation will be invited to participate in the trial. In this visit we will record maternal characteristics and medical history and perform an ultrasound scan to determine chorionicity, confirm gestational age from the measurement of the fetal crown-rump length of the bigger twin, diagnose any major fetal abnormalities, screen for chromosomal abnormalities based on the first-trimester combined test.
Women fulfilling the inclusion criteria will be invited to participate in the randomised trial of aspirin (150 mg/day) vs. placebo from 11 to 14 until 36 weeks’ gestation. The aim of the trial is to examine if the prophylactic use of low-dose aspirin from the first-trimester of pregnancy in women with twin pregnancy can reduce the incidence of preeclampsia with delivery <37 weeks’ gestation.
The trial is powered for a 50% reduction in incidence of preterm preeclampsia from an anticipated 5.5% in the placebo group to 2.75% in the aspirin group. For a power of 90%, using a two sided test at the 5% level of significance, it is necessary to randomise 2,400 pregnancies.
Effects of dietary nitrate supplementation on pregnancies complicated by chronic and new onset hypertension - The BEET-BP Trial
This is a double-blind placebo controlled multicentre randomised trial. All participants with new onset hypertension (gestational hypertension or preeclampsia or chronic hypertension) presenting between 24 to 36 weeks’ gestation fulfilling the eligibility criteria will be offered recruitment into the trial. Participants will be randomly allocated to either 70 mL beetroot juice concentrate or 70 mL nitrate deplete beetroot juice placebo on a 1:1 basis. This juice will be taken at the same time each morning until delivery.
The primary outcome of this trial is to determine the effect of beetroot juice on gestational age of delivery secondary to preeclampsia. The sample size is calculated with the aim to prove a 10 day delay in gestation of delivery with preeclampsia in the beetroot juice concentrate arm versus the nitrate deplete beetroot juice arm. Assuming the study population will be comprised of 75% gestational hypertension and 25% chronic hypertension with rates of superimposed preeclampsia of 40% in the gestational hypertension group and 30% in the chronic hypertension group. 320 women (160 in each arm) will need to be randomised for a power of 90%. Assuming 80% acceptance to randomisation, 400 patients will need to be screened.
Gestational treatment with Ursodeoxycholic Acid compared to Placebo to Reduce Severity of Gestational Diabetes Mellitus diagnosed at 24-28 weeks’ gestation (GUARDS trial)
This is a double-blind placebo-controlled randomised single site trial. The participating centre in Spain will be Clinic University Hospital “Virgen de la Arrixaca” in Murcia. Participants who are diagnosed with gestational diabetes mellitus will be offered participation. After written informed consent, eligible women will be randomly assigned to ursodeoxycholic acid 500 mg twice per day or placebo at 24+0 to 30+6 weeks’ gestation until birth. The primary outcome of the study is maternal fasting glucose concentration at 36 weeks of gestation.
Clinical efficacy, mechanisms of action and acceptability of ursodeoxycholic acid will be assessed in study participants. Clinical efficacy will be measured by maternal-infant glucose control using conventional capillary and novel continuous glucose measures and standard clinical measures for serum lipids. Acceptability will be measured by patient compliance (pill counts) and confirmed by serum measurements of individual bile acids.
A study size of 204 participants will provide sufficient statistical power whilst allowing for a 40% withdrawal rate. This gives 90% power to detect the primary outcome of a difference in maternal fasting glucose at 36 weeks of 6% (0.28mmol/L), consistent with previously reported differences with ursodeoxycholic acid treatment for non-alcoholic fatty liver disease, and equivalent to the difference in glucose categories between which differences in large for gestation neonates, primary caesarean section, cord blood serum C-peptide level >90th centile and clinical neonatal hypoglycaemia were evident in the HAPO study. Using two-sided calculations with alpha 0.5, 61 women per arm would be required to determine this reduction with 90% power.