Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia

NCT ID: NCT03466333

Last Updated: 2021-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-05
• Study Completion Date: 2020-09-11

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Investigational medicinal product

Oral enalapril maleate once daily: 5mg for 1 week, then 10mg for 2 weeks, then 20mg maintenance (for total of 6 months postpartum)

Group Type: EXPERIMENTAL

Enalapril Maleate

Intervention Type: DRUG

Enalapril maleate will be encapsulated; participants will take the drug once a day for 6 months following delivery.

Placebo

Oral placebo once daily for 6 months postpartum

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

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.

Observational arm

For participants who decline to be take part in the interventional part of the study (decline randomisation to IMP/placebo) however they consent to the observational components of the study (serial echocardiography and biomarkers postpartum).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Enalapril Maleate

Enalapril maleate will be encapsulated; participants will take the drug once a day for 6 months following delivery.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jenny Dr Myers, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Manchester

Locations

Manchester University NHS Foundation Trust

Manchester, Greater Manchester, United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33012200 (View on PubMed)

Other Identifiers

R04725

Identifier Type: -

Identifier Source: org_study_id