Double blind, randomised, placebo-controlled trial to evaluate the efficacy of esomeprazole to treat early onset pre-eclampsia (PIE Trial): a study protocol.
BACKGROUND
Pre-eclampsia is a major complication of pregnancy, globally responsible for 60 000 maternal deaths per year, and far greater numbers of fetal losses. There is no definitive treatment other than delivery. A drug that can quench the disease process could be useful to treat early onset pre-eclampsia, as it could allow pregnancies to safely continue to a gestation where fetal outcomes are significantly improved. We have generated preclinical data to show esomeprazole, a proton pump inhibitor used for gastric reflux, has potent biological effects that makes it a worthwhile therapeutic candidate. Esomeprazole potently decreases soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin secretion from placenta and endothelial cells, and has biological actions to mitigate endothelial dysfunction and oxidative stress.


METHODS
We propose undertaking a phase II, double blind, randomised controlled clinical trial to examine whether administering 40 mg esomeprazole daily may prolong gestation in women with early onset pre-eclampsia. We will recruit 120 women (gestational age of 26+0 to 31+6 weeks) who will be randomised to receive either esomeprazole or an identical placebo. The primary outcome will be the number of days from randomisation to delivery. Secondary outcomes include maternal, fetal and neonatal composite and individual outcomes. Maternal outcomes include maternal death, eclampsia, pulmonary oedema, severe renal impairment, cerebral vascular events and liver haematoma or rupture. Neonatal outcomes include neonatal death within 6 weeks after the due date, intraventricular haemorrhage, necrotising enterocolitis and bronchopulmonary dysplasia. We will examine whether esomeprazole can decrease serum sFlt-1 and soluble endoglin levels and we will record the safety of esomeprazole in these pregnancies.


BACKGROUND
This study has ethical approval (Protocol V.2.4, M14/09/038, Federal Wide assurance Number 00001372, IRB0005239), and is registered with NHREC (ID 3649) and the Pan African Clinical Trial Registry (PACTR201504000771349). Data will be presented at international conferences and published in peer-reviewed journals.
Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Melbourne, Victoria, Australia.
Catherine A
CA
Cluver
Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
Susan P
SP
Walker
The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
Ben W
BW
Mol
Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa.
Gerard B
GB
Theron
Department of Obstetrics and Gynaecology, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa.
David R
DR
Hall
Department of Anaesthetics, Mercy Hospital for Women, University of Melbourne, Melbourne, Victoria, Australia.
Richard
R
Hiscock
Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Melbourne, Victoria, Australia Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
N
N
Hannan
Translational Obstetrics Group, University of Melbourne, Mercy Hospital for Women, Melbourne, Victoria, Australia Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia.
S
S
Tong
D000328:Adult; D002985:Clinical Protocols; D036861:Delivery, Obstetric; D004311:Double-Blind Method; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D011256:Pregnancy Outcome; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome
D054328:Proton Pump Inhibitors; D064098:Esomeprazole
PERINATOLOGY