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Trial registered on ANZCTR


Registration number
ACTRN12618001755224
Ethics application status
Approved
Date submitted
30/07/2018
Date registered
25/10/2018
Date last updated
25/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Can esomeprazole improve outcomes in women at high risk of pre-eclampsia? The ESPRESSO Study
Scientific title
Can esomeprazole improve outcomes in women at high risk of pre-eclampsia? A phase II placebo-controlled randomised multi-centre clinical trial. The ESPRESSO Study
Secondary ID [1] 295204 0
Nil known
Universal Trial Number (UTN)
Trial acronym
ESPRESSO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pre-eclampsia 308340 0
Condition category
Condition code
Reproductive Health and Childbirth 307343 307343 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Esomeprazole 40mg oral tablet at night commencing prior to 16 weeks gestation and continuing until delivery of pregnancy. Required background therapy is aspirin 150mg oral tablet at night commencing prior to 16 weeks gestation and continuing until 36 weeks gestation. Participants will be questioned on compliance at each visit, and a tablet count performed at 28 and 36 weeks
Intervention code [1] 301542 0
Prevention
Comparator / control treatment
Placebo oral microcellulose tablet at night commencing prior to 16 weeks gestation and continuing until delivery of pregnancy. Required background therapy is aspirin 150mg oral tablet at night commencing prior to 16 weeks gestation and continuing until 36 weeks gestation.
Control group
Placebo

Outcomes
Primary outcome [1] 306302 0
Mean arterial pressure, measured by 24 hour ambulatory blood pressure
Timepoint [1] 306302 0
36 weeks gestation.
Secondary outcome [1] 348115 0
MoM mean arterial pressure. The MoM (multiple of the median) of mean arterial pressure will be calculated by computing the ratio of observed mean arterial pressure to expected mean arterial pressure that would be anticipated for maternal characteristics at that specific gestational age. The measured mean arterial pressure will be calculated from a 24 hour ambulatory blood pressure record (see primary outcome measure). The expected mean arterial pressure will be derived from normative data reported in the literature.
Timepoint [1] 348115 0
36 weeks gestation
Secondary outcome [2] 348116 0
Circulating sFlt-1 concentrations, measured in serum samples according to a standard laboratory protocol
Timepoint [2] 348116 0
36 weeks gestation
Secondary outcome [3] 348117 0
Circulating sENG concentrations, measured in serum samples according to a standard laboratory protocol
Timepoint [3] 348117 0
36 weeks gestation
Secondary outcome [4] 348118 0
Circulating PLGF concentrations, measured in serum samples according to a standard laboratory protocol
Timepoint [4] 348118 0
36 weeks gestation
Secondary outcome [5] 348119 0
sFlt-1/PLGF ratio, defined as the sFlt-1 concentration divided by the PLGF concentration
Timepoint [5] 348119 0
36 weeks gestation
Secondary outcome [6] 348120 0
Severity of proteinuria, measured as a continuous variable using protein to creatinine ratio performed on urine sample
Timepoint [6] 348120 0
36 weeks gestation
Secondary outcome [7] 348121 0
Combined prevalence of pre-eclampsia, hypertension or new treatment for hypertension based on medical records
Timepoint [7] 348121 0
At any time during pregnancy
Secondary outcome [8] 348122 0
Gestational age, defined as the estimated date of delivery plus the actual difference (positive or negative) in weeks and days between estimated date of delivery and date of birth. Estimated date of delivery is based on crown-rump length measurements. Date of birth will be obtained from medical record
Timepoint [8] 348122 0
Delivery
Secondary outcome [9] 348123 0
Weight of the baby (to the nearest gram) at delivery, as recorded in the medical record
Timepoint [9] 348123 0
Delivery
Secondary outcome [10] 348124 0
Apgar score as per routine care and recorded in the medical record
Timepoint [10] 348124 0
At 1, 5 and 10 minutes after birth
Secondary outcome [11] 348125 0
Proportion of infants in each randomised group admitted to neonatal intensive care or special care units, obtained from medical records
Timepoint [11] 348125 0
Neonatal hospital discharge
Secondary outcome [12] 348126 0
Length of neonatal hospital stay, defined as the time in days between birth and discharge home of live infant, obtained from medical records
Timepoint [12] 348126 0
Neonatal hospital discharge
Secondary outcome [13] 348127 0
Proportion of infants discharged home alive in each randomised group, obtained from medical records
Timepoint [13] 348127 0
Neonatal hospital discharge

Eligibility
Key inclusion criteria
1. Pregnant women screened at 11+0 to 13+6 weeks gestation and at high risk (>1%) of pre-eclampsia based on the FMF algorithm.
2. Aged 18 years and older
3. Willing and able to comply with all study requirements
4. Willing and able to commence study treatment before 16+0 weeks
5. Signed, written informed consent.

Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Gestation greater than or equal to 16+0 weeks
2. Contradindications to investigational product
3. Contraindications to aspirin
4. Use of esomeprazole for any reason
5. Intention to terminate pregnancy

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Placebo-controlled, multicentre, superiority trial.
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 11228 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 11229 0
John Hunter Hospital - New Lambton
Recruitment hospital [3] 11230 0
The Royal Women's Hospital - Parkville
Recruitment hospital [4] 11231 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [5] 11232 0
Mater Mother's Hospital - South Brisbane
Recruitment hospital [6] 11233 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [7] 11234 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 23101 0
2050 - Camperdown
Recruitment postcode(s) [2] 23102 0
2305 - New Lambton
Recruitment postcode(s) [3] 23103 0
3052 - Parkville
Recruitment postcode(s) [4] 23104 0
5112 - Elizabeth Vale
Recruitment postcode(s) [5] 23105 0
4101 - South Brisbane
Recruitment postcode(s) [6] 23106 0
3084 - Heidelberg
Recruitment postcode(s) [7] 23107 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 299788 0
Government body
Name [1] 299788 0
National Health and Medical Research Council
Address [1] 299788 0
GPO Box 1421, Canberra ACT 2601
Country [1] 299788 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
c/o NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building
92-94 Parramatta Road
Camperdown NSW 2050
Country
Australia
Secondary sponsor category [1] 300542 0
None
Name [1] 300542 0
Address [1] 300542 0
Country [1] 300542 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300675 0
Sydney Local Health District Ethics Review Committee (RPAH Zone)
Ethics committee address [1] 300675 0
Research Ethics and Governance Office,
Royal Prince Alfred Hospital,
Missenden Road,
Camperdown NSW 2050
Ethics committee country [1] 300675 0
Australia
Date submitted for ethics approval [1] 300675 0
24/10/2017
Approval date [1] 300675 0
07/12/2017
Ethics approval number [1] 300675 0

Summary
Brief summary
The risk of pre-eclampsia (elevated blood pressure in pregnancy) can be predicted through a screening test at 11-13+6 weeks' gestation. Previous work has shown that 'high risk' women benefit from taking aspirin through their pregnancy - resulting in a 62% reduction in pre-eclampsia prevalence before 37 weeks. Current treatment does not alter the prevalence of term pre-eclampsia (i.e. after 37 weeks). This study will test whether adding another treatment (esomeprazole) will cause a further reduction in blood pressure at the end of pregnancy. Pregnant women will take one esomeprazole or placebo tablet each day from before 16 weeks until delivery, in addition to aspirin, and will have their blood pressure measured throughout the study.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 84430 0
Prof Jon Hyett
Address 84430 0
RPA Women and Babies, Royal Prince Alfred Hospital
Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney

c/o ESPRESSO Coordinating Centre, NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building, 92-94 Parramatta Road,
Camperdown NSW 2050
Country 84430 0
Australia
Phone 84430 0
+61295158777
Fax 84430 0
Email 84430 0
jon.hyett@sydney.edu.au
Contact person for public queries
Name 84431 0
Ms ESPRESSO Coordinator
Address 84431 0
c/o ESPRESSO Coordinating Centre
NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building
92-94 Parramatta Road,
Camperdown NSW 2050
Country 84431 0
Australia
Phone 84431 0
+61295625000
Fax 84431 0
Email 84431 0
espresso@ctc.usyd.edu.au
Contact person for scientific queries
Name 84432 0
Prof Jon Hyett
Address 84432 0
RPA Women and Babies, Royal Prince Alfred Hospital
Discipline of Obstetrics, Gynaecology and Neonatology, University of Sydney

c/o ESPRESSO Coordinating Centre, NHMRC Clinical Trials Centre
Level 6, Medical Foundation Building, 92-94 Parramatta Road,
Camperdown NSW 2050
Country 84432 0
Australia
Phone 84432 0
+61295158777
Fax 84432 0
Email 84432 0
jon.hyett@sydney.edu.au

No information has been provided regarding IPD availability
Summary results
No Results