Clinical trial NCT04613193: Blood Pressure Reduction in Patients With Asymptomatic Aortic VALVE Stenosis
Official title: Blood Pressure Reduction in Patients With Asymptomatic Aortic VALVE Stenosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aortic Valve Stenosis
Hypertension,Essential
Heart Failure
Keywords: Aortic Valve Stenosis
Hypertension
Heart failure
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: Danish Heart Foundation
First posted: 2020-11-03
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. BP-AVALVE I: 60 patients will be randomized (1:1) to either strict BP control (N=30) or conventional treatment (N=30). Treatment period will be 12 months.

2. BP-AVALVE II: 200 patients will be randomized (1:1) to either strict BP control as in study 1 (N=100) or conventional care as in study 1 (N=100). Average treatment period will be 2 (1-3) years.

3. BP-AVALVE III: Patients from BP-AVALVE-II continue in the randomized design until they develop symptoms of AS or have been followed for 10 (7-13) years. Patients will be reexamined at the end of the study period or in case they develop symptoms or LV failure and thus indication of valve replacement.

Since the medicinal products used in this study is not the subject of the trial, the Danish Medicines Agency has classified this study as a clinical trial, in which medicinal products are used as a tool to induce a well-known physiological response. Therefor no further approval from the Danish Medicine Agency is required.
Primary purpose: TREATMENT

Brief summary: The aim of this study is to investigate the effect of strict blood pressure control versus conventional care in patients with asymptomatic moderate to severe aortic valve stenosis.

The study is a randomized (1:1), open label, controlled intervention trial.

Hypothesis:

1. Strict BP control for 12 months reduces the progression of LV remodelling compared to conventional treatment.
2. Strict BP control for 2 years reduces the increase in aortic valve calcification and LV remodelling compared to conventional treatment.
3. Strict BP reduction for up to 10 years reduces the need for aortic valve replacement and cardiovascular events compared to conventional care.


Eligibility criteria: Inclusion Criteria:

* Aortic valve peak velocity (Vmax) of 3.0-5.0 m/s and/or aortic valve area (AVA) ≤ 1.2 cm2
* Blood pressure: SBP \>= 127 mmHg measured by BP-TRU
* LVEF ≥ 50%
* Age \> 18 years
* Safe birth control management (intrauterine devices or hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release)) for women of childbearing potential.
* Negative urine-HCG for women of childbearing potential
* Ability to understand the written patient information and to give informed consent.

Exclusion Criteria:

* Symptoms due to AS
* Symptomatic orthostatic hypotension and/or one minute standing SBP \< 110 mmHg (16).
* Suspicion of secondary hypertension
* Participation in other randomized drug study (device studies accepted)
* Moderat to severe aortic valve regurgitation e.g. vena contracta \> 5 mm, assessed by echocardiography)
* Known or suspected ischemic heart disease (coronary angiography with \>70% stenosis in a major epicardial vessel, symptoms or signs of myocardial ischemia, e.g. angina pectoris, wall motion abnormalities). Patients who have previously undergone complete revascularization of major coronary arteries due to angina pectoris are eligible for inclusion.
* Significant coronary obstructive lesions detected by baseline Cardiac CT that requires a revascularisation procedure.
* eGFR \< 30 ml/min or end-stage renal disease
* Other disease, comorbidity or treatment making the subject unsuitable for study participation as judged by the investigator

Primary outcomes:
measure: Change in LV mass
timeFrame: Changes will be evaluated after an expected average of 12 months treatment
measure: Change in aortic valve CT calcium volume and aortic peak gradient
timeFrame: Changes will be evaluated after an expected average of 2-3 years treatment
measure: Clinical composite endpoint:
timeFrame: Will be evaluated after an expected average of 7-13 years of treatment
Secondary outcomes:
measure: LV mass-cavity ratio.
timeFrame: Through study completion, an average of 1 year
measure: LV myocardial fibrosis
timeFrame: Through study completion, an average of 1 year
measure: Myocardial perfusion during rest and stress
timeFrame: Through study completion, an average of 1 year
measure: Aortic peak and mean gradients
timeFrame: Through study completion, an average of 1 year
measure: Aortic valve area
timeFrame: Through study completion, an average of 1 year
measure: Left ventricular global longitudinal strain
timeFrame: Through study completion, an average of 1 year
measure: Valvolu-arterial impedance
timeFrame: Through study completion, an average of 1 year
measure: NT-proBNP
timeFrame: Baseline and follow-up
measure: Minnesota living with heart failure questionnaire
timeFrame: Through study completion, an average of 1 year
measure: Ambulatory 24-hour blood pressure measurement
timeFrame: Through study completion, an average of 1 year
measure: Dimensions and aortic calcium score of the thoracic aorta.
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Dept. of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99
city: Herning
country: Denmark
facility: Dept. of Cardiology, Herning Hospital
city: Horsens
country: Denmark
facility: Dept. of cardiology, Horsens Hospital
city: Randers
country: Denmark
facility: Dept. of cardiology, Randers Hospital
city: Silkeborg
country: Denmark
facility: Silkeborg Hospital
city: Viborg
country: Denmark
facility: Dept. of cardiology, Viborg Hospital
Study officials:
affiliation: Aarhus University Hospital, Department of Cardiology
name: Henrik Wiggers
role: PRINCIPAL_INVESTIGATOR
References: