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Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

This study has been completed.
Sponsor:
Collaborators:
National Center for Advancing Translational Science (NCATS)
Sanofi-Synthelabo
National Center for Research Resources (NCRR)
Information provided by (Responsible Party):
Jordan D. Miller, Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02049203
First received: January 28, 2014
Last updated: July 5, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Aortic Valve Stenosis Drug: Ataciguat Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Jordan D. Miller, Ph.D., Mayo Clinic:

Primary Outcome Measures:
  • Number of patients experiencing orthostatic hypotension [ Time Frame: Baseline - 14 days ]
    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.

  • The change in blood pressure following the transition from sitting to standing [ Time Frame: Baseline - 14 days ]
    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.

  • The change in blood pressure following progressive head-up tilt [ Time Frame: Baseline - 14 days ]
    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.

  • Subject self-reports of light-headedness/orthostatic intolerance during the standing test and the head-up tilt testing [ Time Frame: Baseline - 14 days ]
    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.


Enrollment: 44
Study Start Date: January 2014
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Placebo gel capsule, dosage matches number of Ataciguat capsules for each respective dose, capsules taken once daily with breakfast for 14 consecutive days.
Drug: Placebo
Other Name: Placebo gel capsule of identical composition to Active group, but does not have active compound.
Active Comparator: Ataciguat
Ataciguat, orally administered gel capsule, 50, 100, or 200 mg, once per day with breakfast for 14 consecutive days
Drug: Ataciguat
Other Name: HMR1766

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02049203

Locations
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Jordan D. Miller, Ph.D.
National Center for Advancing Translational Science (NCATS)
Sanofi-Synthelabo
National Center for Research Resources (NCRR)
Investigators
Principal Investigator: Jordan Miller, PhD Mayo Clinic
  More Information

Responsible Party: Jordan D. Miller, Ph.D., Assistant Professor of Surgery, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02049203     History of Changes
Other Study ID Numbers: 13-005387
UL1RR024150 ( U.S. NIH Grant/Contract )
Study First Received: January 28, 2014
Last Updated: July 5, 2016

Additional relevant MeSH terms:
Constriction, Pathologic
Aortic Valve Stenosis
Pathological Conditions, Anatomical
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction

ClinicalTrials.gov processed this record on September 20, 2017