Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

Phase 1CompletedNCT02049203

Jordan D. Miller, Ph.D.44 enrolled

Overview

This study will determine whether Ataciguat (HMR1766) is well-tolerated in patients with mild to moderate calcific aortic valve stenosis. The primary focus of these studies will be on changes in blood pressure and orthostatic tolerance (i.e., ability to stand up without passing out), and determining whether treatment with Ataciguat results in significant reductions in blood pressure in this patient population.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Aortic Valve Stenosis

Interventions

AtaciguatDRUG

PlaceboDRUG

Eligibility

Sex: ALLMin age: 50 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Age \> 50 years * Male or female sex * Aortic valve area greater than 1.0 cm2 but less than 2.0 cm2 * Aortic valve calcium levels greater than 300 arbitrary units from chest CT * Ejection fraction \>50% Exclusion Criteria: * History of orthostatic intolerance or symptomatic hypotension * Positive pregnancy test during screening visit * Nitrate use or α-antagonist medication use within 24 hours * Systolic blood pressure \<110 mm Hg * Mean systemic arterial pressure \<75 mm Hg * Severe mitral or aortic regurgitation * Retinal or optic nerve problems * Recent (≤30 days) acute coronary syndrome * Oxygen saturation \<90% on room air * Congenital valve disease * Hepatic dysfunction/elevated liver enzymes * Prescription of drugs known to alter nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling (sildenafil, nitrates, etc.) * History of orthostatic intolerance * Concomitant participation in other trials at Mayo Clinic or elsewhere.

Locations (1)

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Outcomes

Primary Outcomes

Number of patients experiencing orthostatic hypotension

Time frame: Baseline - 14 days

The change in blood pressure following the transition from sitting to standing

The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Transitioning from sitting to standing is a functional test that will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a relevant orthostatic stress.

Time frame: Baseline - 14 days

The change in blood pressure following progressive head-up tilt

The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Tilt table testing will allow us to examine the effects of Ataciguat on blood pressure regulation in response to a tightly controlled orthostatic stress.

Time frame: Baseline - 14 days

Subject self-reports of light-headedness/orthostatic intolerance during the standing test and the head-up tilt testing

The primary objective of the current study is to determine whether Ataciguat (HMR1766) is well-tolerated by patients with moderate calcific aortic valve stenosis. In this particular patient population, incidence of orthostatic intolerance/symptomatic hypotension is a potential concern. Evaluating subject perceptions of light-headedness/orthostatic intolerance will help us to understand the relationship between changes in blood pressure and changes in symptoms in this patient population before and after treatment with Ataciguat.

Data from ClinicalTrials.gov

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