PreeclampsiaNCT04216706
Early Vascular Adjustments to Prevent Preeclampsia
An observational study of Preeclampsia and Small for Gestational Age at Delivery, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. Gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preeclampsia, Small for Gestational Age at Delivery, HELLP Syndrome
- What is being tested?
- tailored pharmaceutical treatment
- How many people
- 314 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Nov 2014to 1 Mar 2020
- Phase
- Observational
- 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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Pregnant women who had preeclampsia in their first pregnancy
Who may be able to join
- first pregnancy complicated by preeclampsia
- admitted to an extensive non-pregnant cardiovascular and metabolic risk factor assessment
Who cannot join
- women without an ongoing pregnancy after 24 weeks' gestational age
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Early Vascular Adjustments to Prevent Preeclampsia and Related Complications
Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. Gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth. Early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. The investigators aim to evaluate early cardiovascular adjustments during pregnancy in a high-risk population, and to pharmaceutically adjust deviant cardiovascular adaptations with beta-blockade, centrally acting sympatholytic agents or vasodilating agents when appropriate to prevent adverse effects on neonatal birth weight.
Read the detailed description
Healthy pregnancy is accompanied by major hemodynamic changes that benefit the uteroplacental circulation. A first-trimester drop in vascular resistance triggers several compensatory mechanisms, amongst an increase in blood volume and cardiac output, to maintain blood pressure. These adaptations continue and stand until delivery.
Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. On the one hand, gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth.
Antihypertensive therapy based on correction of the hemodynamic imbalance between cardiac output and peripheral resistance seems an effective strategy to improve blood pressure control in hypertensive pregnant women. Even more sophisticated, early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. One randomized controlled trial treated pregnant women with an augmented cardiac output with a selective beta-blocker, which resulted in a decreased prevalence of preeclampsia from 18% in the placebo group to 4% in the atenolol group (p = 0.04), at a cost of 440gram birth weight.
In line of this reasoning, the investigators aimed to evaluate early cardiovascular adjustments during pregnancy in a high-risk population (i.e. women with preeclampsia in their first pregnancy). In this health care traject, women with deviant adaptation to pregnancy were advised tailored medication, i.e. beta-blockade in women with an pronounced high cardiac output profile effectuated by a high heart rate, and a vasodilating agent in women with a high-resistance hemodynamic profile. Women with a mixed hemodynamic profile were advised a centrally acting sympatholytic agent. The investigators aimed to retrospectively compare outcome of women attending this health care project with women who received care as usual in their second pregnancy.
- Being tested
- tailored pharmaceutical treatment
- Keywords
- cardiac output, total peripheral vascular resistance, hemodynamic parameters, adaptation to pregnancy, tailored treatment
- Medical subject headings
- Pre-Eclampsia, HELLP Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tailored pharmaceutical treatmentDrug
Also called Betablocker, Centrally acting sympatholytic agent, Calcium channel blocker
Tailored medication is advised in women with inadequate hemodynamic adaptation to pregnancy. Type of medication depends on total peripheral vascular resistance and heart rate. In short, women with a low peripheral vascular resistance in parallel with a high heart rate are advised a betablocker (labetalol), while a vasodilating agent (calcium channel blocker, nifedipine) was advised in women with a high total peripheral vascular resistance in combination with a low heart rate. Women with suboptimal adaptation to pregnancy without an extreme pronounced vascular profile are advised a centrally acting sympatholytic agent (methyldopa).
| Study group | Role | What they receive |
|---|---|---|
| Tailored treatment advise in suboptimal adaptation | High-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment are invited to participate in a follow-up program at four time-points during a subsequent pregnancy (i.e. at 12, 16, 20 and 30 weeks of gestational age). This program is additive to regular pregnancy check-ups, and all women are otherwise managed by their referring physicians. The aim of this program is to evaluate adaptation of maternal hemodynamic parameters in response to pregnancy, and to adjust deviant adaptation with tailored antihypertensive medication. Participation in this program is on voluntary basis, and not restricted to severity of complications in the first pregnancy. Receives: Drug: tailored pharmaceutical treatment | |
| Care as usual during pregnancy | High-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment who do not participate in the additional follow-up program. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of women that develop preeclampsia
Preeclampsia is defined as new-onset hypertension along with de novo proteinuria or other maternal organ dysfunction (i.e. renal insufficiency, liver involvement, neurological complications or hematological complications) after 20 weeks of gestation in previously normotensive women, or superimposed on chronic hypertension.
Measured: during pregnancy, or up to 6 weeks after delivery
Secondary outcomes (8)
Number of women that develop HELLP syndrome
HELLP-syndrome is defined as hemolysis (LDH > 600 U/L), elevated liver enzymes (AST -aspartate aminotransferase- and ALT -alanine aminotransferase- > 70 U/L) and low platelets (platelet count < 100.109/L)
Measured: during pregnancy, or up to 6 weeks after delivery
Number of women that develop eclampsia
Seizures in women with preeclampsia
Measured: during pregnancy, or up to 6 weeks after delivery
Number of women that have placental abruption during pregnancy
Measured: During pregnancy or at delivery
Stillbirth
Number of stillbirths in included women
Measured: during pregnancy until delivery
Neonatal mortality
Number of neonatal demise related to prematurity or as a consequence of maternal disease related to preeclampsia
Measured: after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother
Neonatal birth weight
birth weight of neonates
Measured: measured at delivery
Neonatal birth weight centile
Neonatal birth weight centile (adjusted for sex of neonate, gestational age at delivery and maternal parity)
Measured: birth weight and other parameters measured at delivery
Pregnancy outcome of women included
Gestational age at delivery
Measured: at delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2020
- Study start1 Nov 2014
- Primary completion1 Jan 2020
- Study completion1 Mar 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 PreeclampsiaStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 314 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04216706
- Sponsor's protocol ID
- 14-4-118
- Status last verified
- Dec 2019
- First submitted
- 19 Dec 2019
- Last updated
- 11 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mulder EG, Ghossein-Doha C, Cauffman E, Lopes van Balen VA, Schiffer VMMM, Alers RJ, Oben J, Smits L, van Kuijk SMJ, Spaanderman MEA. Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy. Hypertension. 2021 Jun;77(6):2045-2053. doi: 10.1161/HYPERTENSIONAHA.120.16502. Epub 2021 Apr 5.
PubMed 33813842
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Vascular Adjustments to Prevent Preeclampsia and Related Complications
- ClinicalTrials.gov ID
- NCT04216706
- Acronym / sponsor ID
- 14-4-118
- Keywords
- cardiac output, total peripheral vascular resistance, hemodynamic parameters, adaptation to pregnancy, tailored treatment
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 314 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- 1 Nov 2014 (actual)
- Primary completion
- 1 Jan 2020 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 3 Jan 2020 (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.
Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. Gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth. Early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. The investigators aim to evaluate early cardiovascular adjustments during pregnancy in a high-risk population, and to pharmaceutically adjust deviant cardiovascular adaptations with beta-blockade, centrally acting sympatholytic agents or vasodilating agents when appropriate to prevent adverse effects on neonatal birth weight.
Detailed description
Healthy pregnancy is accompanied by major hemodynamic changes that benefit the uteroplacental circulation. A first-trimester drop in vascular resistance triggers several compensatory mechanisms, amongst an increase in blood volume and cardiac output, to maintain blood pressure. These adaptations continue and stand until delivery.
Women destined to develop gestational hypertensive complications often exhibit deviant hemodynamic adaptation patterns before overt clinical disease. On the one hand, gestational hypertension and late onset preeclampsia are associated with an exaggerated rise in cardiac output on top of a higher prepregnant value, whereas a shallow rise in cardiac output and the lack of a peripheral resistance drop predisposes to the much less common early onset-preeclampsia along with impaired fetal growth.
Antihypertensive therapy based on correction of the hemodynamic imbalance between cardiac output and peripheral resistance seems an effective strategy to improve blood pressure control in hypertensive pregnant women. Even more sophisticated, early treatment of altered cardiac output and peripheral resistance adjustments might prevent development of gestational hypertensive complications. One randomized controlled trial treated pregnant women with an augmented cardiac output with a selective beta-blocker, which resulted in a decreased prevalence of preeclampsia from 18% in the placebo group to 4% in the atenolol group (p = 0.04), at a cost of 440gram birth weight.
In line of this reasoning, the investigators aimed to evaluate early cardiovascular adjustments during pregnancy in a high-risk population (i.e. women with preeclampsia in their first pregnancy). In this health care traject, women with deviant adaptation to pregnancy were advised tailored medication, i.e. beta-blockade in women with an pronounced high cardiac output profile effectuated by a high heart rate, and a vasodilating agent in women with a high-resistance hemodynamic profile. Women with a mixed hemodynamic profile were advised a centrally acting sympatholytic agent. The investigators aimed to retrospectively compare outcome of women attending this health care project with women who received care as usual in their second pregnancy.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tailored treatment advise in suboptimal adaptation | – | Drug: tailored pharmaceutical treatmentHigh-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment are invited to participate in a follow-up program at four time-points during a subsequent pregnancy (i.e. at 12, 16, 20 and 30 weeks of gestational age). This program is additive to regular pregnancy check-ups, and all women are otherwise managed by their referring physicians. The aim of this program is to evaluate adaptation of maternal hemodynamic parameters in response to pregnancy, and to adjust deviant adaptation with tailored antihypertensive medication. Participation in this program is on voluntary basis, and not restricted to severity of complications in the first pregnancy. |
| Care as usual during pregnancy | – | –High-risk women admitted to a non-pregnant cardiovascular and cardiometabolic risk factor assessment who do not participate in the additional follow-up program. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Pregnant women who had preeclampsia in their first pregnancy
Key inclusion criteria (2 listed)
- first pregnancy complicated by preeclampsia
- admitted to an extensive non-pregnant cardiovascular and metabolic risk factor assessment
Key exclusion criteria (1 listed)
- women without an ongoing pregnancy after 24 weeks' gestational age
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 |
|---|---|---|
| tailored pharmaceutical treatmentAlso: Betablocker, Centrally acting sympatholytic agent, Calcium channel blockerTailored medication is advised in women with inadequate hemodynamic adaptation to pregnancy. Type of medication depends on total peripheral vascular resistance and heart rate. In short, women with a low peripheral vascular resistance in parallel with a high heart rate are advised a betablocker (labetalol), while a vasodilating agent (calcium channel blocker, nifedipine) was advised in women with a high total peripheral vascular resistance in combination with a low heart rate. Women with suboptimal adaptation to pregnancy without an extreme pronounced vascular profile are advised a centrally acting sympatholytic agent (methyldopa). | Drug | Tailored treatment advise in suboptimal adaptation |
Primary outcome
Number of women that develop preeclampsia
Time frame: during pregnancy, or up to 6 weeks after delivery
Preeclampsia is defined as new-onset hypertension along with de novo proteinuria or other maternal organ dysfunction (i.e. renal insufficiency, liver involvement, neurological complications or hematological complications) after 20 weeks of gestation in previously normotensive women, or superimposed on chronic hypertension.
8 secondary outcomes
Number of women that develop HELLP syndrome
Time frame: during pregnancy, or up to 6 weeks after delivery
Number of women that develop eclampsia
Time frame: during pregnancy, or up to 6 weeks after delivery
Number of women that have placental abruption during pregnancy
Time frame: During pregnancy or at delivery
Stillbirth
Time frame: during pregnancy until delivery
Neonatal mortality
Time frame: after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother
Neonatal birth weight
Time frame: measured at delivery
Neonatal birth weight centile
Time frame: birth weight and other parameters measured at delivery
Pregnancy outcome of women included
Time frame: at delivery
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 11 Mar 2020.
- Derived from this study: PubMed 33813842Mulder EG, Ghossein-Doha C, Cauffman E, Lopes van Balen VA, Schiffer VMMM, Alers RJ, Oben J, Smits L, van Kuijk SMJ, Spaanderman MEA. Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy. Hypertension. 2021 Jun;77(6):2045-2053. doi: 10.1161/HYPERTENSIONAHA.120.16502. Epub 2021 Apr 5.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Preeclampsia and Small for Gestational Age at Delivery, run by Maastricht University Medical Center at 1 site in Netherlands.
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 2 inclusion and 1 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 11 Mar 2020. 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 Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Number of women that develop preeclampsia (time frame: during pregnancy, or up to 6 weeks after delivery). 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 NCT04216706, 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 11 Mar 2020; AzTrials last refreshed its copy on 4 Nov 2026.