Clinical trial NCT03466333: Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia
Official title: Feasibility Study on the Effects of Postnatal Enalapril on Maternal Cardiovascular Function Following Preterm Pre-eclampsia.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cardiovascular Diseases
Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis)
Keywords: preterm pre-eclampsia
cardiovascular dysfunction
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2018-03-15
Enrollment: 118
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind randomised controlled trial (40 participants) Eligible women who decline to take art in the interventional arm, can consent to the observational arm of the study (up to 40 participants)
Primary purpose: TREATMENT

Brief summary: This is a double blind randomised controlled feasibility study investigating the effect of postnatal enalapril on cardiovascular function in women who have had preterm pre-eclampsia. Participants will be randomised to 6 months of enalapril or placebo within 3 days of delivery. Cardiovascular function will be assessed using serial echocardiography and biomarkers.

Detailed description: Pre-eclampsia (PE) is a condition in pregnancy, identified by a combination of high blood pressure and protein in the urine. It affects 3-5% pregnancies. Women with preterm PE (pPE; delivery before 37 weeks) frequently develop abnormal heart function after pregnancy, which increases their risk of heart disease in later life. Subtle changes in heart function have also been shown to increase the chance of a woman getting PE again in her next pregnancy. Despite this, research to date has focused on the pregnancy and relatively little is known about what happens after pregnancy and whether outcomes can be improved with treatment. sFlt is a protein that prevents blood vessel growth and causes blood vessel constriction. sFlt levels are raised in pPE and correlate with the degree of abnormal heart function. In animal studies, sFlt has been shown to directly cause injury to the heart and it is therefore possible that sFlt mediates pPE associated heart damage. Angiotensin converting enzyme (ACE) inhibitors are commonly used to protect against heart damage following myocardial infarction, but their use has never been tested following pPE.

Objectives:

1. To characterise abnormal heart function following pPE
2. To determine if this can be modified by treatment with enalapril.

Study design:

Women who have had pPE, will be randomly allocated to enalapril or placebo from delivery for 6 months. Heart function will be assessed using blood tests and ultrasound scans (echocardiography). This will allow us to learn more about how pPE affects the heart (from the placebo group) and measure the protective effect of enalapril on the heart. Recruitment rates and acceptability of the intervention will also be assessed in this feasibility study.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of pPE in this pregnancy requiring delivery \< 37 weeks gestation: new or worsening hypertension \>20 weeks with proteinuria or other features suggestive of PE (abnormal haematological, biochemical parameters, fetal growth restriction (FGR) and/or abnormal sFlt:PlGF (\>85)).
* Biochemical / haematological cut-offs:
* Platelet count \<100 x109/L
* Alanine amino transferase \> 50units/L
* Creatinine \>90mmol/L
* FGR:
* Abdominal circumference (AC) / estimated fetal weight (EFW) \<3rd centile
* Or 2 of the following:
* AC/EFW \<10th centile
* AC/EFW crossing centiles by \>2 quartiles
* Cerebroplacental ratio \<5th centile
* Umbilical artery PI \>95th centile
* At time of randomisation:
* Postpartum, within 3 days of delivery
* Aged 18 years or over
* Able to provide informed consent
* Serum creatinine \<100 mmol/l

Exclusion Criteria:

* Inability to consent
* Known cardiac disease
* Contraindication to ACE inhibitors
* Renal artery stenosis

Primary outcomes:
measure: Process outcome
timeFrame: 24 months
measure: Clinical outcome
timeFrame: 32 months
Secondary outcomes:
measure: Process outcome
timeFrame: 32 months
measure: Clinical outcome (echocardiography measures)
timeFrame: 32 months
measure: Clinical outcome (biomarkers)
timeFrame: 32 months
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: Greater Manchester
Study officials:
affiliation: The University of Manchester
name: Jenny Dr Myers, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ormesher L, Higson S, Luckie M, Roberts SA, Glossop H, Trafford A, Cottrell E, Johnstone ED, Myers JE. Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):: A Randomized Double-Blind Placebo-Controlled Feasibility Trial. Hypertension. 2020 Dec;76(6):1828-1837. doi: 10.1161/HYPERTENSIONAHA.120.15875. Epub 2020 Oct 5.