Early Vascular Adjustments During Hypertensive Pregnancy

NCT ID: NCT02531490

Last Updated: 2021-03-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 368 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-01
• Study Completion Date: 2023-04-30

Brief Summary

Paradoxical fetal and maternal results of studies have led to inconsistent use of antihypertensive drugs or no treatment at all in mild to moderate gestational hypertension in the Netherlands. However, none of the studies have taken the individual maternal circulatory state or the contemplated blood pressure response into account. Hypertension may be accompanied by high (hyperdynamic vasodilated profile), normal (normodynamic profile) of low (hypodynamic vasoconstrictive profile) cardiac output, and preeclampsia is not restricted to one circulatory profile. Therefore antihypertensive drugs should be viewed upon as correctors of the hemodynamic state rather than solely reducers of blood pressure. Without taking the maternal hemodynamic profile and condition into account, generic antihypertensive treatment can be expected to result in disappointing, inadequate and paradoxical results. The investigators hypothesize that in mild to moderate hypertension, personalized hemodynamically guided antihypertensive therapy (with target systolic and diastolic blood pressure <130/80mmHg), prevents the progression to severe hypertension and/or preeclampsia compared to no treatment, without the alleged side-effects.

Conditions

Hypertension, Pregnancy-Induced; Pre-Eclampsia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

randomized, interventiongroup

Women with a hyperdynamic vasodilated profile, characterized by a mean arterial pressure (MAP)/ Heart rate (Hr) ratio ≤ 1.1 are prescribed a beta-blocker. Women with a hypodynamic vasoconstrictive profile (MAP/Hr ratio ≥ 1.4) are prescribed nifedipine. Women with normodynamic profile (MAP/Hr ratio in between 1.1 and 1.4) are prescribed Methyldopa.

Group Type: ACTIVE_COMPARATOR

Labetalol

Intervention Type: DRUG

Nifedipine

Intervention Type: DRUG

Methyldopa

Intervention Type: DRUG

randomized, control-group

Women who give informed consent for randomization, and are randomized to the control group will not be medicinally treated for mild to moderate gestational hypertension.

Group Type: NO_INTERVENTION

No interventions assigned to this group

not-randomized, control-group

Women who do not want to be randomized, but who give informed consent for follow-up on their data until discharge after delivery. They will receive standard care, i.e. no medication is prescribed for mild to moderate gestational hypertension.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Labetalol

Intervention Type: DRUG

Nifedipine

Intervention Type: DRUG

Methyldopa

Intervention Type: DRUG

Other Intervention Names

Trandate; Adalat; Aldomet

Eligibility Criteria

Inclusion Criteria

• Patients ages 18years or older
• Before 37 weeks of gestational age;
• Diagnosed with mild to moderate gestational hypertension

Exclusion Criteria

• Women with severe hypertension: systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 110mmHg.
• Women with chronic hypertension who are already on antihypertensive drugs. If no antihypertensive drugs are used yet, women with pre-existent hypertension are eligible to participate.
• Women diagnosed with preeclampsia or eclampsia in the current pregnancy.
• Women who are not able to comprehend the study outline.
• Women who have already participated in this study cannot be included a second time.
• Women who have a (relative) contra-indication for one of the possible prescribed medications (for example women who have tested positive for antinuclear antibodies, which is a contraindication for Methyldopa).
• Women who intend to terminate the pregnancy
• Women who have a fetus with a major anomaly or chromosomal abnormality

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Maastricht University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marc Spaanderman, professor

Role: PRINCIPAL_INVESTIGATOR

Maastricht University Medical Centre

Locations

Maastricht UMC

Maastricht, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Eva Mulder, MD

Role: CONTACT

eva.mulder@mumc.nl

0031650504243

Marc Spaanderman, professor

Role: CONTACT

marc.spaanderman@mumc.nl

0031433874774

Facility Contacts

Eva Mulder

Role: primary

eva.mulder@mumc.nl

References

Schutte JM, Schuitemaker NW, van Roosmalen J, Steegers EA; Dutch Maternal Mortality Committee. Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands. BJOG. 2008 May;115(6):732-6. doi: 10.1111/j.1471-0528.2008.01702.x.

Reference Type: BACKGROUND

PMID: 18410657 (View on PubMed)

Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014 Feb 6;(2):CD002252. doi: 10.1002/14651858.CD002252.pub3.

Reference Type: BACKGROUND

PMID: 24504933 (View on PubMed)

Easterling TR, Benedetti TJ, Schmucker BC, Millard SP. Maternal hemodynamics in normal and preeclamptic pregnancies: a longitudinal study. Obstet Gynecol. 1990 Dec;76(6):1061-9.

Reference Type: BACKGROUND

PMID: 2234714 (View on PubMed)

Valensise H, Vasapollo B, Gagliardi G, Novelli GP. Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension. 2008 Nov;52(5):873-80. doi: 10.1161/HYPERTENSIONAHA.108.117358. Epub 2008 Sep 29.

Reference Type: BACKGROUND

PMID: 18824660 (View on PubMed)

Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002 May;39(5):982-8. doi: 10.1161/01.hyp.0000016176.16042.2f.

Reference Type: BACKGROUND

PMID: 12019280 (View on PubMed)

Mulder E, Ghossein-Doha C, Appelman E, van Kuijk S, Smits L, van der Zanden R, van Drongelen J, Spaanderman M. Study protocol for the randomized controlled EVA (early vascular adjustments) trial: tailored treatment of mild hypertension in pregnancy to prevent severe hypertension and preeclampsia. BMC Pregnancy Childbirth. 2020 Dec 12;20(1):775. doi: 10.1186/s12884-020-03475-w.

Reference Type: DERIVED

PMID: 33308198 (View on PubMed)

Other Identifiers

METC152017

Identifier Type: -

Identifier Source: org_study_id