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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
368
Maastricht UMC
Maastricht, Netherlands
RECRUITINGnumber of patients with severe gestational hypertension
Systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 110mmHg, measured at every visit
Time frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
number of patients with preeclampsia
Preeclampsia is defined as the coexistence of de novo hypertension after 20 weeks of gestation and one or more of the following new-onset conditions: 1. Proteinuria (spot urine protein/creatinine ≥ 30g/mol or ≥ 300mg/day or at least 1 g/L \[2+\] on dipstick testing). 2. Other maternal organ dysfunction: * Renal insufficiency (creatinine levels ≥ 90μmol/L); * Liver involvement (elevated transaminases: ASAT ≥31 U/L and/or ALAT ≥34U/L); * Neurological complications (hyperreflexia when accompanied by clonus and/or severe headaches, persistent visual scotomata, altered mental status, eclampsia); * Haematological complications (thrombocytopenia, platelet count below 150.000/dL, disseminated intravascular coagulation, haemolysis).
Time frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate.
hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
Time frame: 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
hemodynamic profile by mean arterial pressure/heart rate ratio
hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
Time frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography
cardiac output can be derived from these values + heart rate
Time frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
left ventricular volume after diastole and systole measured by transthoracic echocardiography
ejection fraction can be derived from these values
Time frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography
cardiac output can be derived from these values + heart rate
Time frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
left ventricular volume after diastole and systole measured by transthoracic echocardiography
ejection fraction can be derived from these values
Time frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy.
Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) \<=0.43 with a Left Ventricular Mass index (LVMi) of \<95 gram/m2. Concentric hypertrophy is defined as a RWT \<0.43 with a LVMi of ≥95 gram/m2.
Time frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy.
Echocardiographic concentric left ventricular (LV) remodelling and hypertrophy. Concentric remodeling is defined as a relative wall thickness (RWT) \<=0.43 with a Left Ventricular Mass index (LVMi) of \<95 gram/m2. Concentric hypertrophy is defined as a RWT \<0.43 with a LVMi of ≥95 gram/m2.
Time frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
health status of the newborn by Apgar score
scored by gynecologist or paediatrician on a scale of 1 to 10
Time frame: assessed immediately after delivery
prevalence of small for gestational age infancy
birth weight and percentile combined with gestational age at delivery
Time frame: assessed at delivery date
prevalence of premature neonates
gestational age at delivery
Time frame: assessed at delivery date
number of a composite of adverse neonatal outcomes
Stillbirth, perinatal mortality, morbidity: chronic lung disease, neonatal sepsis, severe intra-ventricular haemorrhage (IVH) \> grade II, periventricular leucomalacia \> grade I, and necrotizing enterocolitis. Days on ventilation support, length of admission in neonatal intensive care, and total days in hospital until 3 months corrected age.
Time frame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks
maternal well-being questionnaire,
Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy
Time frame: 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
number of assessed maternal complications
Composite of maternal complications including: mortality, stroke, eclampsia, blindness, uncontrolled hypertension, respiratory failure, birth related variables, needed level of care
Time frame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week
gestational age at the moment of progression to primary outcome.
Time frame: from baseline/inclusion until a study event is reached (up to 18 weeks after inclusion), with an expected average of 4 weeks.
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