Cardiovascular DiseasesPhase 2PICk-UPNCT03466333
Postnatal Enalapril to Improve Cardiovascular fUnction Following Preterm Pre-eclampsia
A Phase 2 study testing Enalapril Maleate in people with Cardiovascular Diseases and Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis), run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 16 years and older, women only
- Conditions the study is for
- Cardiovascular Diseases, Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis)
- What is being tested?
- Enalapril Maleate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 5 Sep 2018to 11 Sep 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 17Show fewer
- 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
Who cannot join
- Inability to consent
- Known cardiac disease
- Contraindication to ACE inhibitors
- Renal artery stenosis
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Manchester University NHS Foundation Trust
Manchester, Greater Manchester, M13 9WL
About this study
Official title: Feasibility Study on the Effects of Postnatal Enalapril on Maternal Cardiovascular Function Following Preterm Pre-eclampsia.
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.
Read the 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:
- To characterise abnormal heart function following pPE
- 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.
- Being tested
- Enalapril Maleate, Placebo oral capsule
- Keywords
- preterm pre-eclampsia, cardiovascular dysfunction
- Medical subject headings
- Cardiovascular Diseases, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enalapril MaleateDrug
Enalapril maleate will be encapsulated; participants will take the drug once a day for 6 months following delivery.
Placebo oral capsuleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Drug: Enalapril Maleate |
| Placebo | Placebo comparator | Oral placebo once daily for 6 months postpartum Receives: 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). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Process outcome
Recruitment rate (number of women eligible, recruited and completing the study per month)
Measured: 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.
Measured: 32 months
Secondary outcomes (3)
Process outcome
Acceptability of the intervention to postnatal women.
Measured: 32 months
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)
Measured: 32 months
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).
Measured: 32 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start5 Sep 2018
- Primary completion11 Sep 2020
- Study completion11 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Jenny Dr Myers, MBBS PhD, Principal investigator, The University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466333
- Sponsor's protocol ID
- R04725
- Acronym
- PICk-UP
- Status last verified
- Feb 2021
- First submitted
- 8 Mar 2018
- Last updated
- 24 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33012200
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study on the Effects of Postnatal Enalapril on Maternal Cardiovascular Function Following Preterm Pre-eclampsia.
- ClinicalTrials.gov ID
- NCT03466333
- Acronym / sponsor ID
- PICk-UP / R04725
- Keywords
- preterm pre-eclampsia, cardiovascular dysfunction
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- 5 Sep 2018 (actual)
- Primary completion
- 11 Sep 2020 (actual)
- Study completion
- 11 Sep 2020 (actual)
- First posted
- 15 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To characterise abnormal heart function following pPE
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- 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)
| Arm | Type | Receives |
|---|---|---|
| Investigational medicinal product | Experimental | Drug: Enalapril MaleateOral enalapril maleate once daily: 5mg for 1 week, then 10mg for 2 weeks, then 20mg maintenance (for total of 6 months postpartum) |
| Placebo | Placebo comparator | Drug: Placebo oral capsuleOral placebo once daily for 6 months postpartum |
| 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). |
Who may qualify
- Ages
- 16 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (4 listed)
- Inability to consent
- Known cardiac disease
- Contraindication to ACE inhibitors
- Renal artery stenosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enalapril MaleateEnalapril maleate will be encapsulated; participants will take the drug once a day for 6 months following delivery. | Drug | Investigational medicinal product |
| Placebo oral capsuleThe 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. | Drug | Placebo |
Primary outcome
Process outcome
Time frame: 24 months
Recruitment rate (number of women eligible, recruited and completing the study per month)
Clinical outcome
Time frame: 32 months
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.
3 secondary outcomes
Process outcome
Time frame: 32 months
Clinical outcome (echocardiography measures)
Time frame: 32 months
Clinical outcome (biomarkers)
Time frame: 32 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2021.
- Derived from this study: PubMed 33012200Ormesher 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jenny Dr Myers, MBBS PhD principal investigator
The University of Manchester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enalapril Maleate in people with Cardiovascular Diseases and Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis), run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Process outcome (time frame: 24 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03466333, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2021.