Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia

NCT03466333 | Completed Phase 2 DMC

• 1 other identifier: R04725
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

preterm pre-eclampsia; cardiovascular dysfunction

Outcome Measures

Primary Outcomes (2)

• Process outcome

  Recruitment rate (number of women eligible, recruited and completing the study per month)

  24 months

• 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 Outcomes (3)

• Process outcome

  32 months

• Clinical outcome (echocardiography measures)

  32 months

• Clinical outcome (biomarkers)

  32 months

Study Arms (3)

Investigational medicinal product

EXPERIMENTAL

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

Drug: Enalapril Maleate

Placebo

PLACEBO COMPARATOR

Oral placebo once daily for 6 months postpartum

Drug: Placebo oral capsule

Observational arm

NO INTERVENTION

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).

Interventions

Enalapril Maleate DRUG

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

Investigational medicinal product

Placebo oral capsule 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.

Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead

Study Sites (1)

Manchester University NHS Foundation Trust

Manchester, Greater Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33012200 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Disease

Interventions

Enalapril

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jenny Dr Myers, MBBS PhD

  The University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 15, 2018
• Study Start: September 5, 2018
• Primary Completion: September 11, 2020
• Study Completion: September 11, 2020
• Last Updated: February 24, 2021

Record last verified: 2021-02

Locations

GB (1)