A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial

William M. Hague; Leonie Callaway; Jennifer Chambers; Lucy Chappell; Suzette Coat; Jiska de Haan-Jebbink; Marloes Dekker; Peter Dixon; Jodie Dodd; Maria Fuller; Sanne Gordijn; Dorothy Graham; Oskari Heikinheimo; Annemarie Hennessy; Risto Kaaja; Teck Yee Khong; Laura Lampio; Jennie Louise; Angela Makris; Corey Markus; Hanns Ulrich Marschall; Philippa Middleton; Ben W. Mol; Jonathan Morris; John P. Newnham; Caroline Ovadia; Michael Peek; Antonia Shand; Michael Stark; Jim Thornton; Susanna Timonen; Susan Walker; David Warrilow; Catherine Williamson

doi:10.1186/s12884-020-03481-y

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial

William M. Hague^*, Leonie Callaway, Jennifer Chambers, Lucy Chappell, Suzette Coat, Jiska de Haan-Jebbink, Marloes Dekker, Peter Dixon, Jodie Dodd, Maria Fuller, Sanne Gordijn, Dorothy Graham, Oskari Heikinheimo, Annemarie Hennessy, Risto Kaaja, Teck Yee Khong, Laura Lampio, Jennie Louise, Angela Makris, Corey MarkusHanns Ulrich Marschall, Philippa Middleton, Ben W. Mol, Jonathan Morris, John P. Newnham, Caroline Ovadia, Michael Peek, Antonia Shand, Michael Stark, Jim Thornton, Susanna Timonen, Susan Walker, David Warrilow, Catherine Williamson

^*Corresponding author for this work

Women & Children's Health

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

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.

Original language	English
Article number	51
Journal	BMC Pregnancy and Childbirth
Volume	21
Issue number	1
DOIs	https://doi.org/10.1186/s12884-020-03481-y
Publication status	Published - Dec 2021

Keywords

Bile acids
Cholestatic pruritus
Intrahepatic cholestasis of pregnancy
Maternal and neonatal health outcomes
Rifampicin
Ursodeoxycholic acid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hague, W. M., Callaway, L., Chambers, J., Chappell, L., Coat, S., de Haan-Jebbink, J., Dekker, M., Dixon, P., Dodd, J., Fuller, M., Gordijn, S., Graham, D., Heikinheimo, O., Hennessy, A., Kaaja, R., Khong, T. Y., Lampio, L., Louise, J., Makris, A., ... Williamson, C. (2021). A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy and Childbirth, 21(1), Article 51. https://doi.org/10.1186/s12884-020-03481-y

Hague, William M. ; Callaway, Leonie ; Chambers, Jennifer et al. / A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy : the TURRIFIC randomised trial. In: BMC Pregnancy and Childbirth. 2021 ; Vol. 21, No. 1.

@article{4ebf72fd807d4c6ba42f08d5960581ac,

title = "A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial",

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.",

keywords = "Bile acids, Cholestatic pruritus, Intrahepatic cholestasis of pregnancy, Maternal and neonatal health outcomes, Rifampicin, Ursodeoxycholic acid",

author = "Hague, {William M.} and Leonie Callaway and Jennifer Chambers and Lucy Chappell and Suzette Coat and {de Haan-Jebbink}, Jiska and Marloes Dekker and Peter Dixon and Jodie Dodd and Maria Fuller and Sanne Gordijn and Dorothy Graham and Oskari Heikinheimo and Annemarie Hennessy and Risto Kaaja and Khong, {Teck Yee} and Laura Lampio and Jennie Louise and Angela Makris and Corey Markus and Marschall, {Hanns Ulrich} and Philippa Middleton and Mol, {Ben W.} and Jonathan Morris and Newnham, {John P.} and Caroline Ovadia and Michael Peek and Antonia Shand and Michael Stark and Jim Thornton and Susanna Timonen and Susan Walker and David Warrilow and Catherine Williamson",

year = "2021",

month = dec,

doi = "10.1186/s12884-020-03481-y",

language = "English",

volume = "21",

journal = "BMC Pregnancy and Childbirth",

issn = "1471-2393",

publisher = "BioMed Central",

number = "1",

}

Hague, WM, Callaway, L, Chambers, J, Chappell, L, Coat, S, de Haan-Jebbink, J, Dekker, M, Dixon, P, Dodd, J, Fuller, M, Gordijn, S, Graham, D, Heikinheimo, O, Hennessy, A, Kaaja, R, Khong, TY, Lampio, L, Louise, J, Makris, A, Markus, C, Marschall, HU, Middleton, P, Mol, BW, Morris, J, Newnham, JP, Ovadia, C, Peek, M, Shand, A, Stark, M, Thornton, J, Timonen, S, Walker, S, Warrilow, D & Williamson, C 2021, 'A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial', BMC Pregnancy and Childbirth, vol. 21, no. 1, 51. https://doi.org/10.1186/s12884-020-03481-y

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial. / Hague, William M.; Callaway, Leonie; Chambers, Jennifer et al.
In: BMC Pregnancy and Childbirth, Vol. 21, No. 1, 51, 12.2021.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy

T2 - the TURRIFIC randomised trial

AU - Hague, William M.

AU - Callaway, Leonie

AU - Chambers, Jennifer

AU - Chappell, Lucy

AU - Coat, Suzette

AU - de Haan-Jebbink, Jiska

AU - Dekker, Marloes

AU - Dixon, Peter

AU - Dodd, Jodie

AU - Fuller, Maria

AU - Gordijn, Sanne

AU - Graham, Dorothy

AU - Heikinheimo, Oskari

AU - Hennessy, Annemarie

AU - Kaaja, Risto

AU - Khong, Teck Yee

AU - Lampio, Laura

AU - Louise, Jennie

AU - Makris, Angela

AU - Markus, Corey

AU - Marschall, Hanns Ulrich

AU - Middleton, Philippa

AU - Mol, Ben W.

AU - Morris, Jonathan

AU - Newnham, John P.

AU - Ovadia, Caroline

AU - Peek, Michael

AU - Shand, Antonia

AU - Stark, Michael

AU - Thornton, Jim

AU - Timonen, Susanna

AU - Walker, Susan

AU - Warrilow, David

AU - Williamson, Catherine

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

KW - Bile acids

KW - Cholestatic pruritus

KW - Intrahepatic cholestasis of pregnancy

KW - Maternal and neonatal health outcomes

KW - Rifampicin

KW - Ursodeoxycholic acid

UR - http://www.scopus.com/inward/record.url?scp=85099226730&partnerID=8YFLogxK

U2 - 10.1186/s12884-020-03481-y

DO - 10.1186/s12884-020-03481-y

M3 - Article

AN - SCOPUS:85099226730

SN - 1471-2393

VL - 21

JO - BMC Pregnancy and Childbirth

JF - BMC Pregnancy and Childbirth

IS - 1

M1 - 51

ER -

Hague WM, Callaway L, Chambers J, Chappell L, Coat S, de Haan-Jebbink J et al. A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial. BMC Pregnancy and Childbirth. 2021 Dec;21(1):51. doi: 10.1186/s12884-020-03481-y

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial

Abstract

Keywords

UN SDGs

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