Phase III trial in IntrahepaTic CHolestasis of pregnancy (ICP) to Evaluate urSodeoxycholic acid (UDCA) in improving perinatal outcomes

Intrahepatic cholestasis of pregnancy (ICP) is the commonest liver disease in pregnancy Affected women itch and have abnormal liver blood tests It is important to diagnose ICP because it is associated with risks for the unborn baby Blood tests in the mother may show high levels of bile acids, which can increase the risk of the baby being born early and, in severe cases, being stillborn At present the main drug used to treat ICP is ursodeoxycholic acid (UDCA) Our pilot study showed that women with ICP are willing to take part in a trial comparing UDCA with a placebo (an identical tablet not containing the drug) Our trial also suggested that UDCA may protect the unborn baby from poor outcomes, but the study was not large enough to be certain A recent study that combined the results of several similar trials also showed that UDCA may improve the outcome for the baby in ICP However, the current guideline from the Royal College of Obstetricians and Gynaecologists (RCOG) states, Women should be informed of the lack of robust data concerning protection against stillbirth and safety to the fetus or neonate Lack of robust data means that the trials did not have a large enough number of women taking part Our larger trial would address this problem If it shows that UDCA protects babies, the RCOG could be clearer about its recommendations The RCOG Guideline matters because this is what most doctors use as a guide for how to treat women with ICP The main part of this study will be a clinical trial to compare the effect of UDCA or placebo treatment on the rate of adverse outcomes in ICP As several studies have reported an increased rate of poor outcomes in ICP pregnancies with higher bile acid levels in the mother, we plan to make sure that at least a fifth of women who participate in the study have higher bile acid levels (>40µM/L) In the other part of the study we will collect samples from some of the mothers and babies to try and understand why ICP causes preterm birth and how it can cause the baby to be sick or die We know that ICP babies have higher rates of breathing problems and spend longer on special care baby units We do not know whether this is due to the mother and baby having high bile acid levels or because ICP pregnancies are often delivered early because doctors worry about the risk of stillbirth in this condition This part of the study will try and find out why these problems happen and will also aim to find out how UDCA may prevent these complications We will ask for some samples including blood, urine and faeces from the pregnant mother and placenta and umbilical cord blood (after the baby has been delivered) In a small number of women with severe disease we will ask for samples of amniotic fluid before delivery to allow measurement of bile acids and other substances that show how mature the baby's lungs are Women have told us that they are willing to give us these samples to help find out the answers If we know that the baby's lungs are not mature, we can give the mother a treatment to help reduce the chance of the baby having breathing problems when it is born The fluid may also show whether the baby has opened its bowels ( passing meconium ) inside the womb which can mean that the baby is stressed and the doctors may want to deliver the baby sooner This research will give vital information to help doctors understand and try and prevent the poor outcomes for the baby in ICP pregnancies