Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

Aortic Valve Stenosis Clinical Trial

Official title:

A Phase Ib Randomized, Placebo-controlled, Double-blinded Study Evaluating the Safety of Ataciguat (HMR1766) in Patients With Moderate Calcific Aortic Valve Stenosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02049203
• Other study ID #: 13-005387
• Secondary ID: UL1RR024150
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2014
• Last updated: July 5, 2016
• Start date: January 2014
• Est. completion date: March 2015

Study information

• Verified date: July 2016
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 a-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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Drug:
• Ataciguat

• Placebo

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (4)

Lead Sponsor	Collaborator
Jordan D. Miller, Ph.D.	National Center for Advancing Translational Science (NCATS), National Center for Research Resources (NCRR), Sanofi-Synthelabo

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients experiencing orthostatic hypotension	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.	Baseline - 14 days	Yes
Primary	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.	Baseline - 14 days	Yes
Primary	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.	Baseline - 14 days	Yes
Primary	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.	Baseline - 14 days	Yes