Blood Pressure Reduction in Patients With Asymptomatic Aortic VALVE Stenosis (BP-AVALVE)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Aortic Valve Stenosis; Hypertension,Essential
• Intervention / Treatment: Other: Blood presssure reduction

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Henrik Wiggers, MD, PhD; Email: henrikwiggers@dadlnet.dk
• Study Contact Backup: Name: Jonas A Povlsen, MD; Phone Number: +452270282; Email: jonapovl@rm.dk

Study Locations

• Denmark
  • Aarhus, Denmark
    • Recruiting
    • Dept. of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99
    • Contact: Henrik Wiggers
  • Herning, Denmark
    • Not yet recruiting
    • Dept. of Cardiology, Herning Hospital
    • Contact: Morten Bøttcher
  • Horsens, Denmark
    • Not yet recruiting
    • Dept. of cardiology, Horsens Hospital
    • Contact: Karen Kaae Dodt
  • Randers, Denmark
    • Not yet recruiting
    • Dept. of cardiology, Randers Hospital
    • Contact: Liv Gøtzsche
  • Silkeborg, Denmark
    • Not yet recruiting
    • Silkeborg Hospital
    • Contact: Lars Frost
  • Viborg, Denmark
    • Not yet recruiting
    • Dept. of cardiology, Viborg Hospital
    • Contact: Jens Refsgaard

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Strict BP intervention group; SBP < 120 mmHg and a reduction in SBP of >= 15 mmHg	Other: Blood presssure reduction; Patients will be uptitrated in antihypertensive treatment until the treatment target is achieved.
Other: Conventional BP control group; In patients < 75 years: SBP = 135 mmHg In patients >/= 75 years: SBP = 145 mmHg	Other: Blood presssure reduction; Patients will be uptitrated in antihypertensive treatment until the treatment target is achieved.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in LV mass	LV mass as measured by cardiac MR	Changes will be evaluated after an expected average of 12 months treatment
Change in aortic valve CT calcium volume and aortic peak gradient	Cardiac CT and Echocardiography	Changes will be evaluated after an expected average of 2-3 years treatment
Clinical composite endpoint:	Major cardiovascular events including death from cardiovascular causes, aortic valve replacement, non-fatal myocardial infarction, hospitalization for unstable angina pectoris, heart failure, coronary artery bypass surgery, percutaneous coronary intervention, and haemorrhagic and non-haemorrhagic stroke, new onset atrial fibrillation.	Will be evaluated after an expected average of 7-13 years of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV mass-cavity ratio.	Cardiac MR	Through study completion, an average of 1 year
LV myocardial fibrosis	Cardiac MR	Through study completion, an average of 1 year
Myocardial perfusion during rest and stress	Cardiac MR	Through study completion, an average of 1 year
Aortic peak and mean gradients	Echocardiography	Through study completion, an average of 1 year
Aortic valve area	Echocardiography	Through study completion, an average of 1 year
Left ventricular global longitudinal strain	Echocardiography	Through study completion, an average of 1 year
Valvolu-arterial impedance	Echocardiography	Through study completion, an average of 1 year
NT-proBNP	Blood test	Baseline and follow-up
Minnesota living with heart failure questionnaire	Questionnaire	Through study completion, an average of 1 year
Ambulatory 24-hour blood pressure measurement	Ambulatory 24-hour blood pressure measurement	Through study completion, an average of 1 year
Dimensions and aortic calcium score of the thoracic aorta.	cardiac CT	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Henrik Wiggers
• Collaborators: Danish Heart Foundation
• Investigators: Principal Investigator: Henrik Wiggers, Aarhus University Hospital, Department of Cardiology

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2019
• Primary Completion (Anticipated): January 1, 2031
• Study Completion (Anticipated): June 1, 2031

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: October 27, 2020
• First Posted (Actual): November 3, 2020

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 27, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Hypertension; Heart failure; Aortic Valve Stenosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Hypertension; Aortic Valve Stenosis; Constriction, Pathologic; Essential Hypertension
• Other Study ID Numbers: BP-AVALVE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No