Brief Title
Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)
Official Title
Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)
Brief Summary
The current trial is designed to assess the safety and efficacy of sustained oral
administration of inorganic nitrate in patients with severe aortic stenosis and to assess the
mechanisms by which inorganic nitrate enhances oxygen uptake and exercise capacity in this
population.
Detailed Description
This is a randomized double-blind crossover clinical trial, in which 22 subjects who
underwent transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS) three
or more months prior to enrollment will receive the following 2 interventions, in randomized
order: (1) Potassium nitrate (KNO3), at a dose of 12-18 mmol/d by mouth for 4 weeks, or; (2)
Potassium chloride (KCl), at a dose of 12-18 mmol/d by mouth for 4 weeks. A 1-week washout
period will be introduced between the 2 interventions. The purpose of the trial is to test
the safety of KNO3 and its efficacy on a number of clinical and physiologic endpoints in
subjects who underwent TAVR for severe AS.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Total Work Performed During a Maximal-effort Exercise Test
Secondary Outcome
Systemic Vasodilator Response to Exercise
Condition
Aortic Valve Stenosis
Intervention
Potassium Nitrate
Study Arms / Comparison Groups
Potassium Nitrate (KNO3)
Description: Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
5
Start Date
May 1, 2018
Completion Date
May 23, 2019
Primary Completion Date
March 13, 2019
Eligibility Criteria
Inclusion Criteria:
1. Adults aged 50-90 years of age
2. Diagnosis of severe aortic stenosis prior to aortic valve repair
3. Successful trancatheter aortic valve repair via transfemoral procedural approach or
successful surgical aortic valve repair at least three months prior to enrollment
4. Stable medical therapy: no addition/removal/changes in anti-hypertensive medications,
or beta-blockers in the preceding 30 days.
Exclusion Criteria
1. Supine systolic blood pressure (SBP) < 100 mmHg OR supine diastolic blood pressure
(DBP) <60 mmHg
2. Poorly controlled hypertension, as defined as SBP > 160 mmHg OR DBP > 100 mmHg
3. Pregnancy. Women of childbearing potential will undergo a pregnancy test during the
screening visit
4. Atrial fibrillation within the prior 8 weeks before enrollment
5. Inability/unwillingness to exercise
6. Moderate or greater mitral regurgitation or aortic/peri-valvular regurgitation, any
degree of mitral stenosis, severe right-sided valvular disease, or presence of a
mitral prosthetic valve.
7. Moderate or severe patient prosthesis mismatch, as defined by Effective Orifice Area
Index < 0.85 cm2/m2
8. Hypertrophic, infiltrative, or inflammatory cardiomyopathy
9. Pericardial disease
10. Current angina
11. Acute coronary syndrome or coronary intervention within the past 2 months
12. Primary pulmonary arteriopathy
13. Clinically significant lung disease as defined by: Chronic Obstructive pulmonary
disease meeting Stage III or greater GOLD criteria, treatment with oral steroids
within the past 6 months for an exacerbation of obstructive lung disease, or the use
of daytime supplemental oxygen
14. Ischemia on stress testing without subsequent revascularization (during the screening
visit)
15. Treatment with phosphodiesterase inhibitors that cannot be withheld
16. Treatment with organic nitrates
17. Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x
ULN, Albumin <3.0 g/dL)
18. eGFR < 30 mL/min/1.73 m2
19. G6PD deficiency. For males of African, Asian or Mediterranean decent, this will be
evaluated prior to drug administration. A qualitative test positive for deficiency or
a quantitative test with clinically significant G6PD deficiency (<60% of normal
activity) will prompt exclusion from the trial (prior to drug administration).
20. History of methemoglobinemia or methemoglobin level >5% at baseline visit
21. Serum K>5.0 mEq/L
22. Severe right ventricular dysfunction.
23. Any medical condition that, in the opinion of the investigator, will interfere with
the safe completion of the study.
Gender
All
Ages
50 Years - 90 Years
Accepts Healthy Volunteers
No
Contacts
Julio Chirinos, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03483051
Organization ID
828994
Responsible Party
Sponsor
Study Sponsor
University of Pennsylvania
Study Sponsor
Julio Chirinos, MD, Principal Investigator, University of Pennsylvania
Verification Date
June 2020