Trial record 4 of 7 for:    Mitral Valve Prolapse | Open Studies | NIH, U.S. Fed

Safety of Ataciguat in Patients With Moderate Calcific Aortic Valve Stenosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Mayo Clinic
Sponsor:
Collaborators:
Sanofi-Synthelabo
Information provided by (Responsible Party):
Jordan D. Miller, Ph.D., Mayo Clinic
ClinicalTrials.gov Identifier:
NCT02049203
First received: January 28, 2014
Last updated: January 29, 2014
Last verified: January 2014
  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
Mild to Moderate Calcific Aortic Valve Stenosis
Drug: Ataciguat
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 Mayo Clinic:

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


Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: May 2014 (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
Genders Eligible for Study:   Both
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 Recruiting
Rochester, Minnesota, United States, 55905
Contact: Pam Engrav    507-255-6938    engrav.pamela@mayo.edu   
Principal Investigator: Jordan D Miller, PhD         
Principal Investigator: Maurice E Sarano, MD         
Principal Investigator: Hartzell V Schaff, MD         
Sub-Investigator: Michael J Joyner, MD         
Sponsors and Collaborators
Jordan D. Miller, Ph.D.
Sanofi-Synthelabo
Investigators
Principal Investigator: Jordan Miller, PhD Mayo Clinic
  More Information

No publications provided

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
Study First Received: January 28, 2014
Last Updated: January 29, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 19, 2014