- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03483051
Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS) (PULSE-AS)
June 3, 2020 updated by: University of Pennsylvania
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
5
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
50 years to 90 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Adults aged 50-90 years of age
- Diagnosis of severe aortic stenosis prior to aortic valve repair
- Successful trancatheter aortic valve repair via transfemoral procedural approach or successful surgical aortic valve repair at least three months prior to enrollment
- Stable medical therapy: no addition/removal/changes in anti-hypertensive medications, or beta-blockers in the preceding 30 days.
Exclusion Criteria
- Supine systolic blood pressure (SBP) < 100 mmHg OR supine diastolic blood pressure (DBP) <60 mmHg
- Poorly controlled hypertension, as defined as SBP > 160 mmHg OR DBP > 100 mmHg
- Pregnancy. Women of childbearing potential will undergo a pregnancy test during the screening visit
- Atrial fibrillation within the prior 8 weeks before enrollment
- Inability/unwillingness to exercise
- 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.
- Moderate or severe patient prosthesis mismatch, as defined by Effective Orifice Area Index < 0.85 cm2/m2
- Hypertrophic, infiltrative, or inflammatory cardiomyopathy
- Pericardial disease
- Current angina
- Acute coronary syndrome or coronary intervention within the past 2 months
- Primary pulmonary arteriopathy
- 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
- Ischemia on stress testing without subsequent revascularization (during the screening visit)
- Treatment with phosphodiesterase inhibitors that cannot be withheld
- Treatment with organic nitrates
- Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin <3.0 g/dL)
- eGFR < 30 mL/min/1.73 m2
- 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).
- History of methemoglobinemia or methemoglobin level >5% at baseline visit
- Serum K>5.0 mEq/L
- Severe right ventricular dysfunction.
- Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Potassium Nitrate (KNO3)
Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks.
|
Potassium nitrate capsules will consist of potassium nitrate (KNO3-) crystals [610 mg, corresponding to 6.03 mmoles of NO3-] with 190mg of lactose monohydrate, spray dried, NF.
The dose for this trial will be 18 mmoles of NO3-per day, given as one capsule (6 mmoles) three times a day.
|
Sham Comparator: Potassium Chloride
Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks.
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Potassium chloride capsules will consist of potassium chloride (KCl), granular, USP (450mg) plus lactose monohydrate, spray dried, NF (300mg).
The dose for this trial will be 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Total Work Performed During a Maximal-effort Exercise Test
Time Frame: 9 weeks
|
The effect of KNO3 on exercise capacity, quantified as Total work performed during a maximal-effort exercise test;
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9 weeks
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Peak Oxygen Uptake (VO2) During a Maximal Effort Exercise Test
Time Frame: 9 weeks
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The effect of KNO3 on exercise capacity, quantified as: Peak oxygen consumption (VO2) during a symptom-limited maximal effort exercise test.
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9 weeks
|
Quality of Life Score
Time Frame: 9 weeks
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The effect of KNO3 on quality of life, assessed using the Kansas City Cardiomyopathy Questionnaire.
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9 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Systemic Vasodilator Response to Exercise
Time Frame: 9 weeks
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The effect of KNO3 on systemic vasodilator response, measured by change in systemic vascular resistance, during a symptom-limited maximal exercise test,
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9 weeks
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Left Ventricle Diastolic Function
Time Frame: 9 weeks
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The effect of KNO3 on left ventricle diastolic filling parameters (measured with echocardiography at rest and after peak exercise)
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9 weeks
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Myocardial Systolic Strain
Time Frame: 9 weeks
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The effect of KNO3 on myocardial strain (assessed with speckle-tracking echocardiography)
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9 weeks
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Late Systolic Left Ventricle Load
Time Frame: 9 weeks
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The effect of KNO3 on last systolic left ventricle load from wave reflections (assessed via comprehensive aortic pressure-flow regulations, using arterial tonometry and Doppler echocardiography)
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9 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Julio Chirinos, MD, University of Pennsylvania
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2018
Primary Completion (Actual)
March 13, 2019
Study Completion (Actual)
May 23, 2019
Study Registration Dates
First Submitted
February 15, 2018
First Submitted That Met QC Criteria
March 28, 2018
First Posted (Actual)
March 29, 2018
Study Record Updates
Last Update Posted (Actual)
June 17, 2020
Last Update Submitted That Met QC Criteria
June 3, 2020
Last Verified
June 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 828994
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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