Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia

Cardiovascular Diseases Clinical Trial

— PICk-UP  

Official title:

Feasibility Study on the Effects of Postnatal Enalapril on Maternal Cardiovascular Function Following Preterm Pre-eclampsia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03466333
• Other study ID #: R04725
• Status: Completed
• Phase: Phase 2
• Start date: September 5, 2018
• Est. completion date: September 11, 2020

Study information

• Verified date: February 2021
• Source: Manchester University NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 118
• Est. completion date: September 11, 2020
• Est. primary completion date: September 11, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Eclampsia
• Pre-Eclampsia
• Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis)

Intervention

Drug:
• Enalapril Maleate
Enalapril maleate will be encapsulated; participants will take the drug once a day for 6 months following delivery.
• Placebo oral capsule
The placebo will be encapsulated; participants will take the drug once a day for 6 months following delivery. It will be identical in appearance to the IMP.

Locations

Country	Name	City	State
United Kingdom	Manchester University NHS Foundation Trust	Manchester	Greater Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Manchester University NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Process outcome	Recruitment rate (number of women eligible, recruited and completing the study per month)	24 months
Primary	Clinical outcome	Reduction in total vascular resistance (TVR) (from baseline to 6 months post-randomisation following treatment with enalapril, compared with placebo). Whilst TVR is the nominated primary endpoint for this feasibility study, the choice of primary outcome for the definitive trial remains uncertain.	32 months
Secondary	Process outcome	Acceptability of the intervention to postnatal women.	32 months
Secondary	Clinical outcome (echocardiography measures)	A change in other parameters of cardiac function (including: E/E' ratio, tricuspid valve regurgitation, left atrial volume index (LAVi), left ventricular function (LVEF), cardiac output (CO), stroke volume (SV), relative wall thickness (RWT), left ventricular mass index (LVMi), concentric/eccentric remodelling, global longitudinal strain (GLS), left ventricular (LV) basal strain, LV apical strain)	32 months
Secondary	Clinical outcome (biomarkers)	A change in biomarkers (high sensitivity troponin (hs-cTnT), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt1), N-terminal pro-brain natriuretic peptide (NTproBNP), nitric oxide end products (NOx).	32 months