Clinical trial NCT02531490: Early Vascular Adjustments During Hypertensive Pregnancy
Official title: Personalized Hemodynamically Guided Antihypertensive Treatment in Pregnant Women With Mild to Moderate Hypertension: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension, Pregnancy-Induced
Pre-Eclampsia
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2015-08-24
Enrollment: 368
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: number of patients with severe gestational hypertension
timeFrame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
measure: number of patients with preeclampsia
timeFrame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary outcomes:
measure: the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate.
timeFrame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks
measure: hemodynamic profile by mean arterial pressure/heart rate ratio
timeFrame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
measure: diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography
timeFrame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
measure: left ventricular volume after diastole and systole measured by transthoracic echocardiography
timeFrame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
measure: diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography
timeFrame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
measure: left ventricular volume after diastole and systole measured by transthoracic echocardiography
timeFrame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
measure: cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy.
timeFrame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
measure: cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy.
timeFrame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
measure: health status of the newborn by Apgar score
timeFrame: assessed immediately after delivery
measure: prevalence of small for gestational age infancy
timeFrame: assessed at delivery date
measure: prevalence of premature neonates
timeFrame: assessed at delivery date
measure: number of a composite of adverse neonatal outcomes
timeFrame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks
measure: maternal well-being questionnaire,
timeFrame: at baseline and each study visit/follow up measurement (at 1 week, 2 weeks, etc. up to 23 weeks after inclusion. The expected average is 8 weeks
measure: number of assessed maternal complications
timeFrame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week
measure: gestational age at the moment of progression to primary outcome.
timeFrame: from baseline/inclusion until a study event is reached (up to 18 weeks after inclusion), with an expected average of 4 weeks.
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht UMC
Study officials:
affiliation: Maastricht University Medical Centre
name: Marc Spaanderman, professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.