Personalized Hemodynamically Guided Antihypertensive Treatment in Pregnant Women With Mild to Moderate Hypertension: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 入组人数
- 368
- 试验地点
- 1
- 主要终点
- number of patients with preeclampsia
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients ages 18years or older
- •Before 37 weeks of gestational age;
- •Diagnosed with mild to moderate gestational hypertension
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Labetalol (Drug)
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.
干预措施: Nifedipine (Drug)
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.
干预措施: Methyldopa (Drug)
结局指标
主要结局
number of patients with preeclampsia
时间窗: 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).
number of patients with severe gestational hypertension
时间窗: 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
次要结局
- diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography(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(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.(from date of randomization until the date of 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.(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(from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion))
- gestational age at the moment of progression to primary outcome.(from baseline/inclusion until a study event is reached (up to 18 weeks after inclusion), with an expected average of 4 weeks.)
- health status of the newborn by Apgar score(assessed immediately after delivery)
- prevalence of small for gestational age infancy(assessed at delivery date)
- prevalence of premature neonates(assessed at delivery date)
- number of a composite of adverse neonatal outcomes(from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks)
- maternal well-being questionnaire,(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(from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week)