Early Vascular Adjustments During Hypertensive Pregnancy

Pre-Eclampsia Clinical Trial

— EVA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02531490
• Other study ID #: METC152017
• Status: Recruiting
• Phase: Phase 4
• Start date: January 1, 2015
• Est. completion date: April 2023

Study information

• Verified date: March 2021
• Source: Maastricht University Medical Center
• Contact: Eva Mulder, MD
• Phone: 0031650504243
• Email: eva.mulder[@]mumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 368
• Est. completion date: April 2023
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Eclampsia
• Hypertension
• Hypertension, Pregnancy-Induced
• Pre-Eclampsia

Intervention

Drug:
• Labetalol

• Nifedipine

• Methyldopa

Locations

Country	Name	City	State
Netherlands	Maastricht UMC	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Maastricht University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (5)

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. Review. Update in: Cochrane Database Syst Rev. 2018 Oct 01;10:CD002252. — View 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. — View 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. — View Citation

Taler SJ, Textor SC, Augustine JE. Resistant hypertension: comparing hemodynamic management to specialist care. Hypertension. 2002 May;39(5):982-8. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	number of patients with severe gestational hypertension	Systolic blood pressure = 160mmHg and/or diastolic blood pressure = 110mmHg, measured at every visit	from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Primary	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: Proteinuria (spot urine protein/creatinine = 30g/mol or = 300mg/day or at least 1 g/L [2+] on dipstick testing).; 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).	from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary	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.	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
Secondary	hemodynamic profile by mean arterial pressure/heart rate ratio	hemodynamic profiles will be classified as hyperdynamic, hypodynamic vasocontricted or mixed profile.	from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary	diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography	cardiac output can be derived from these values + heart rate	from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
Secondary	left ventricular volume after diastole and systole measured by transthoracic echocardiography	ejection fraction can be derived from these values	from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
Secondary	diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography	cardiac output can be derived from these values + heart rate	from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary	left ventricular volume after diastole and systole measured by transthoracic echocardiography	ejection fraction can be derived from these values	from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary	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.	from baseline, and every 4 weeks (maximum 6 times, because in max. 23 weeks end of study is reached)
Secondary	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.	from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)
Secondary	health status of the newborn by Apgar score	scored by gynecologist or paediatrician on a scale of 1 to 10	assessed immediately after delivery
Secondary	prevalence of small for gestational age infancy	birth weight and percentile combined with gestational age at delivery	assessed at delivery date
Secondary	prevalence of premature neonates	gestational age at delivery	assessed at delivery date
Secondary	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.	from delivery up neonates will be followed for the duration of the hospital stay, an expected average of 6 weeks
Secondary	maternal well-being questionnaire,	Reported medication side effects, and maternal well-being by signs and symptoms during pregnancy	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
Secondary	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	from a study event participants will be followed for the duration of hospital stay, an expected average of 1 week
Secondary	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.