Early Vascular Adjustments During Hypertensive Pregnancy

NCT02531490 | Unknown Phase 4

• 1 other identifier: METC152017
• Study Type: interventional
• Target: 368
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension, Pregnancy-Induced; Pre-Eclampsia

Outcome Measures

Primary Outcomes (2)

• 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)

• 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).

  from date of randomization until the date of this study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)

Secondary Outcomes (15)

• 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)

• diameter aortic outflow tract and left ventricular outflow tract measured by transthoracic echocardiography

  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

  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

  from date of randomization until the date of study event, assessed up to 1 week post partum (maximum 23weeks after inclusion)

Study Arms (3)

randomized, interventiongroup

ACTIVE COMPARATOR

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.

Drug: Labetalol; Drug: Nifedipine; Drug: Methyldopa

randomized, control-group

NO INTERVENTION

Women who give informed consent for randomization, and are randomized to the control group will not be medicinally treated for mild to moderate gestational hypertension.

not-randomized, control-group

NO INTERVENTION

Women who do not want to be randomized, but who give informed consent for follow-up on their data until discharge after delivery. They will receive standard care, i.e. no medication is prescribed for mild to moderate gestational hypertension.

Interventions

Labetalol DRUG

Also known as: Trandate

randomized, interventiongroup

Nifedipine DRUG

Also known as: Adalat

randomized, interventiongroup

Methyldopa DRUG

Also known as: Aldomet

randomized, interventiongroup

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients ages 18years or older
• Before 37 weeks of gestational age;
• Diagnosed with mild to moderate gestational hypertension

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht UMC

Maastricht, Netherlands

RECRUITING

Related Publications (6)

• 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.

  PMID: 18410657 BACKGROUND

• 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.

  PMID: 24504933 BACKGROUND

• 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.

  PMID: 2234714 BACKGROUND

• 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.

  PMID: 18824660 BACKGROUND

• 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.

  PMID: 12019280 BACKGROUND

• 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.

  PMID: 33308198 DERIVED

MeSH Terms

Conditions

Hypertension, Pregnancy-Induced; Pre-Eclampsia

Interventions

Labetalol; Nifedipine; Methyldopa

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Salicylamides; Amides; Amines; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dihydroxyphenylalanine; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Marc Spaanderman, professor

  Maastricht University Medical Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eva Mulder, MD

CONTACT

0031650504243; eva.mulder@mumc.nl

Marc Spaanderman, professor

CONTACT

0031433874774; marc.spaanderman@mumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2015
• First Posted: August 24, 2015
• Study Start: January 1, 2015
• Primary Completion: February 1, 2023
• Study Completion: April 1, 2023
• Last Updated: March 24, 2021

Record last verified: 2021-03

Locations

NL (1)