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Early Vascular Adjustments to Prevent Preeclampsia

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ClinicalTrials.gov Identifier: NCT04216706
Recruitment Status : Completed
First Posted : January 3, 2020
Last Update Posted : March 11, 2020
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center

Brief 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 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.

Condition or disease Intervention/treatment
Preeclampsia Small for Gestational Age at Delivery HELLP Syndrome Drug: tailored pharmaceutical treatment

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.

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Study Type : Observational
Actual Enrollment : 314 participants
Observational Model: Case-Control
Time Perspective: Retrospective
Official Title: Early Vascular Adjustments to Prevent Preeclampsia and Related Complications
Actual Study Start Date : November 1, 2014
Actual Primary Completion Date : January 1, 2020
Actual Study Completion Date : March 1, 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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.
Drug: tailored pharmaceutical treatment
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).
Other Names:
  • Betablocker
  • Centrally acting sympatholytic agent
  • Calcium channel blocker

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.



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Number of women that develop HELLP syndrome [ Time Frame: during pregnancy, or up to 6 weeks after delivery ]
    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)

  2. Number of women that develop eclampsia [ Time Frame: during pregnancy, or up to 6 weeks after delivery ]
    Seizures in women with preeclampsia

  3. Number of women that have placental abruption during pregnancy [ Time Frame: During pregnancy or at delivery ]
  4. Stillbirth [ Time Frame: during pregnancy until delivery ]
    Number of stillbirths in included women

  5. Neonatal mortality [ Time Frame: after delivery up to hospital discharge, which is assessed 6 weeks after due date of the mother ]
    Number of neonatal demise related to prematurity or as a consequence of maternal disease related to preeclampsia

  6. Neonatal birth weight [ Time Frame: measured at delivery ]
    birth weight of neonates

  7. Neonatal birth weight centile [ Time Frame: birth weight and other parameters measured at delivery ]
    Neonatal birth weight centile (adjusted for sex of neonate, gestational age at delivery and maternal parity)

  8. Pregnancy outcome of women included [ Time Frame: at delivery ]
    Gestational age at delivery



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Pregnant women who had preeclampsia in their first pregnancy
Criteria

Inclusion Criteria:

  • first pregnancy complicated by preeclampsia
  • admitted to an extensive non-pregnant cardiovascular and metabolic risk factor assessment

Exclusion Criteria:

  • women without an ongoing pregnancy after 24 weeks' gestational age

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04216706


Locations
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Netherlands
Maastricht UMC
Maastricht, Netherlands
Sponsors and Collaborators
Maastricht University Medical Center
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Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT04216706    
Other Study ID Numbers: 14-4-118
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maastricht University Medical Center:
cardiac output
total peripheral vascular resistance
hemodynamic parameters
adaptation to pregnancy
tailored treatment
Additional relevant MeSH terms:
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Pre-Eclampsia
HELLP Syndrome
Hypertension, Pregnancy-Induced
Pregnancy Complications
Calcium Channel Blockers
Sympatholytics
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Autonomic Agents
Peripheral Nervous System Agents