William M Hague1,2, Leonie Callaway3,4, Jennifer Chambers5, Lucy Chappell5, Suzette Coat6, Jiska de Haan-Jebbink7, Marloes Dekker4, Peter Dixon5, Jodie Dodd6, Maria Fuller6,8, Sanne Gordijn7, Dorothy Graham9, Oskari Heikinheimo10, Annemarie Hennessy11, Risto Kaaja12, Teck Yee Khong6,8, Laura Lampio11, Jennie Louise6, Angela Makris10, Corey Markus8,13, Hanns-Ulrich Marschall14, Philippa Middleton6,15, Ben W Mol16, Jonathan Morris17, John P Newnham9, Caroline Ovadia5, Michael Peek18, Antonia Shand17, Michael Stark6,19, Jim Thornton20, Susanna Timonen12, Susan Walker21, David Warrilow22, Catherine Williamson5. 1. Robinson Research Institute, The University of Adelaide, 55 King William Road, North Adelaide, 5006, South Australia, Australia. bill.hague@adelaide.edu.au. 2. Obstetric Medicine, Women's and Babies' Division, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006, Australia. bill.hague@adelaide.edu.au. 3. Gynaecology, Oncology & Obstetric Medicine, Royal Brisbane and Women's Hospital, Herston, 4029, Queensland, Australia. 4. The University of Queensland, Brisbane, 4072, Queensland, Australia. 5. Women and Children's Health, King's College London, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK. 6. Robinson Research Institute, The University of Adelaide, 55 King William Road, North Adelaide, 5006, South Australia, Australia. 7. Dutch Consortium for Healthcare Evaluation in Obstetrics and Gynaecology (NVOG Consortium), Postbus 20075, Utrecht, 3502 LB, The Netherlands. 8. SA Pathology, Women's and Children's Hospital, 72 King William Road, North Adelaide, 5006, South Australia, Australia. 9. University of Western Australia Division of Obstetrics and Gynaecology, King Edward Memorial Hospital, PO Box 134, Subiaco, Perth, 6904, Western Australia, Australia. 10. Women's Hospital, University of Helsinki and Helsinki University Hospital, P.O. Box 140, Haartmaninkatu 2, Helsinki, HUS 00029, Finland. 11. School of Medicine, Campbelltown Campus, University of Western Sydney, Narellan Rd, Campbelltown, 2560, NSW, Australia. 12. Department of Obstetrics and Gynaecology, Turku University Hospital (TYKS), PO Box 52, Turku, 20521, Finland. 13. Flinders University International Centre for Point-of-Care Testing, College of Medicine & Public Health, GPO Box 2100, Sturt Road, Bedford Park, South Australia, 5042, Australia. 14. Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, SE-413 45, Sweden. 15. SAHMRI Women and Kids, South Australian Health and Medical Research Institute, PO Box 11060, Adelaide, 5001, South Australia, Australia. 16. Obstetrics & Gynaecology Monash Health, Monash University, Clayton, 3800, Victoria, Australia. 17. Paediatrics and Reproductive Medicine, The University of Sydney, Sydney, 2006, New South Wales, Australia. 18. Obstetrics and Gynaecology, Australian National University Medical School, The Canberra Hospital, PO Box 11, Woden, 2606, Australian Capital Territory, Australia. 19. Obstetric Medicine, Women's and Babies' Division, Women's and Children's Hospital, 72 King William Road, North Adelaide, South Australia, 5006, Australia. 20. Obstetrics and Gynaecology, Nottingham University Hospitals NHS Trust, Queen's Medical Centre, Derby Rd, Nottingham, NG7 2UH, UK. 21. Department of Obstetrics and Gynaecology, University of Melbourne, Mercy Hospital for Women, 163 Studley Road, Heidelberg, 3084, Victoria, Australia. 22. Public Health Virology Laboratory, Public and Environmental Health, Forensic and Scientific Services, Health Support Queensland, Department of Health, 39 Kessels Road, Coopers Plains, 4108, Queensland, Australia.
Abstract
BACKGROUND:Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.
RCT Entities:
BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.
Entities:
Keywords:
Bile acids; Cholestatic pruritus; Intrahepatic cholestasis of pregnancy; Maternal and neonatal health outcomes; Rifampicin; Ursodeoxycholic acid
Authors: Lucy C Chappell; Jennifer L Bell; Anne Smith; Louise Linsell; Edmund Juszczak; Peter H Dixon; Jenny Chambers; Rachael Hunter; Jon Dorling; Catherine Williamson; Jim G Thornton Journal: Lancet Date: 2019-08-01 Impact factor: 79.321