Clinical Trial: Early Vascular Adjustments During Hypertensive Pregnancy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Personalized Hemodynamically Guided Antihypertensive Treatment in Pregnant Women With Mild to Moderate Hypertension: a Randomized Controlled Trial

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.

Detailed Summary:
Sponsor: Maastricht University Medical Center

Current Primary Outcome:

  • number of patients with severe gestational hypertension [ Time Frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    Systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 110mmHg, measured at every visit
  • number of patients with preeclampsia [ Time Frame: from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]

    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).


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate. [ 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 profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • hemodynamic profile by mean arterial pressure/heart rate ratio [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
  • diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    cardiac output can be derived from these values + heart rate
  • left ventricular volume after diastole and systole measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    ejection fraction can be derived from these values
  • diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    cardiac output can be derived from these values + heart rate
  • left ventricular volume after diastole and systole measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    ejection fraction can be derived from these values
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
    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.
  • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
    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.
  • health status of the newborn by Apgar score [ Time Frame: assessed immediately after delivery ]
    scored by gynecologist or paediatrician on a scale of 1 to 10
  • prevalence of small for gestational age infancy [ Time Frame: assessed at delivery date ]
    birth weight and percentile combined with gestational age at delivery
  • prevalence of premature neonates [ Time Frame: assessed at delivery date ]
    gestational age at delivery
  • number of a composite of adverse neonatal outcomes [ Time Frame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks ]
    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.
  • maternal well-being questionnaire, [ 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 ]
    Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy
  • number of assessed maternal complications [ Time Frame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week ]
    Composite of maternal complications including: mortality, stroke, eclampsia, blindness, uncontrolled hypertension, respiratory failure, birth

    Original Secondary Outcome:

    • the pattern of change of the hemodynamic profile, measured by the ratio of mean arterial pressure and heart rate. [ 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 profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
    • hemodynamic profile by mean arterial pressure/heart rate ratio [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
      hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.
    • cardiac function measured by transthoracic echocardiography [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
      circulatory status, systolic and diastolic function
    • cardiac function measured by transthoracic echocardiography [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
      circulatory status, systolic and diastolic function
    • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached) ]
      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.
    • cardiac remodeling during pregnancy: number of patients with concentric left ventricular remodeling or concentric hypertrophy. [ Time Frame: from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion) ]
      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.
    • health status of the newborn by Apgar score [ Time Frame: assessed immediately after delivery ]
      scored by gynecologist or paediatrician on a scale of 1 to 10
    • prevalence of small for gestational age infancy and prevalence of premature neonates [ Time Frame: assessed at delivery date ]
      birth weight and percentile, gestational age at delivery
    • number of a composite of adverse neonatal outcomes [ Time Frame: from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks ]
      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.
    • maternal well-being questionnaire, [ 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 ]
      Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy
    • number of assessed maternal complications [ Time Frame: from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week ]
      Composite of maternal complications including: mortality, stroke, eclampsia, blindness, uncontrolled hypertension, respiratory failure, birth related variables, needed level of care
    • 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. ]


    Information By: Maastricht University Medical Center

    Dates:
    Date Received: August 5, 2015
    Date Started: December 2015
    Date Completion: April 2019
    Last Updated: February 4, 2016
    Last Verified: February 2016