TURRIFIC is the Trial of URsodeoxycholic acid versus RIFampicin in severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC study.
Who is heading this trial?
Professor Bill Hague, a researcher and obstetric physician in Adelaide, is leading the trial from The Robinson Research Institute of The University of Adelaide, and you can find a link to it here. Recruitment is taking place in Sweden and Finland, as well as in the UK. The trial is also registered here: https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-004011-44/FI.
What will this trial do?
This trial was started in 2019 and the main objective is to compare the effectiveness of reducing itch between ursodeoxycholic acid (UDCA), the most commonly used medication to treat intrahepatic cholestasis of pregnancy (ICP), with rifampicin (RIF), which is less commonly used.
Secondary objectives are:
- To compare the effect of RIF treatment with UDCA on short-term outcomes for both mother and infant including the length of gestation and the incidence of caesarean section and preterm birth
- To compare the effect of RIF treatment with UDCA on serum concentrations of: bile acids, transaminases, and on metabolites such as serum autotaxin and progesterone sulphated metabolites, and urine glucuronidated 6α-hydroxylated BA.
- To assess the effect of RIF and UDCA on the metabolome and the gut microbiome
- To assess the effect of treatment with RIF compared with UDCA on maternal and fetal outcomes analysed by bile acid transporter genotype.
Who will be recruited to this trial?
Women with ICP before 34 weeks of pregnancy, and whose bile acids are ≥40 μmol/L, are eligible to take part. If they consent, they are then randomised (1:1) to take either UDCA or rifampicin. In addition to the routine samples for managing ICP (bile acids and ALT), extra samples collected (with permission and if available) during the trial include blood, urine, stool, amniotic liquor and, after the birth, the placenta. An itch score is also taken at every visit to the hospital to assess progress in the degree of itch.
How is ICP Support involved?
Our charity has been involved since Bill first started to think about designing TURRIFIC and we are delighted to have been asked to be included in this important trial.
We know that UDCA has benefits for women with ICP whose bile acids are >40 μmol/L (a reduction in the risk of spontaneous premature birth), but we also know that it isn’t quite as good as we’d hoped at reducing itch in ICP, something that the trial PITCHES highlighted. Rifampicin has been used in the UK for some years and again, with varying degrees of success, but it also has to be used with caution as, in some women with ICP, it can worsen the liver. Typically in the UK, rifampicin is offered to women whose bile acids are not improving. However, it is used as an additional drug rather than replacing UDCA. In TURRIFIC, women will initially take only UDCA or rifampicin, but not both. (After an initial period of assessment, it will be possible to add the other treatment.)
It will therefore be good to see whether one or other medication stands out as the better medication to use initially, or whether clinicians are better advised to still consider using both of them to treat ICP in some women.
When will we have any results to share with you?
Like so many trials, the covid-19 pandemic brought recruitment to a halt for a while so progress has been slow, but we hope that, despite these challenges, we will know more by 2024.
What other countries are involved?
Prof Bill Hague
Australia: Northern Adelaide
Dr Melissa Whalan
Australia: SE Sydney (Liverpool and Campbelltown Hospitals)
Prof Annemarie Hennessy and Prof Angela Makris
Australia: Mercy Hospital (Melbourne)
Prof Susan Walker
Finland: Helsinki University Hospital
Prof Oskari Heikinheimo and Dr Laura Lampio
Sweden: Sahlgrenska Hospital, Gothenburg
Prof Hanns-Ulrich Marschall and Dr Ylva Carlsson
Sweden: Karolinska Hospital, Stockholm
Dr Gunilla Ajne and Dr Malin Thorsell
Looking to recruit:
Australia: Southern Adelaide
Dr Jessica Gehlert
Australia: Eastern Sydney
Dr Antonia Shand
Australia: Parramatta, Sydney
Prof Dharmintra Pasupathy
Australia; Northern Sydney
Prof Michael Peek
Prof Leonie Callaway
Australia: SE Melbourne
Prof Ben Mol
Dr Susanna Timonen
Dr Sanne Gordijn and Dr Jelmer Prins
UK: Guy’s, St Thomas’, London
Prof Catherine Williamson and Dr Caroline Ovadia
UK: Nottingham University Hospital
Prof Kate Walker