Aortic Valve StenosisPhase 2PULSE-ASNCT03483051
Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)
A Phase 2 study testing Potassium Nitrate and Potassium Chloride in people with Aortic Valve Stenosis, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Aortic Valve Stenosis
- What is being tested?
- Potassium Nitrate and Potassium Chloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 1 May 2018to 23 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 23Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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.
Read the 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.
- Conditions
- Aortic Valve Stenosis
- Being tested
- Potassium Nitrate, Potassium Chloride
- Keywords
- aortic stenosis, aortic valve replacement
- Medical subject headings
- Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Potassium NitrateDrug
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.
Potassium ChlorideDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Potassium Nitrate (KNO3) | Experimental | Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Receives: Drug: Potassium Nitrate |
| Potassium Chloride | Sham comparator | Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Receives: Drug: Potassium Chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Work Performed During a Maximal-effort Exercise Test
The effect of KNO3 on exercise capacity, quantified as Total work performed during a maximal-effort exercise test;
Measured: 9 weeks
Peak Oxygen Uptake (VO2) During a Maximal Effort Exercise Test
The effect of KNO3 on exercise capacity, quantified as: Peak oxygen consumption (VO2) during a symptom-limited maximal effort exercise test.
Measured: 9 weeks
Quality of Life Score
The effect of KNO3 on quality of life, assessed using the Kansas City Cardiomyopathy Questionnaire.
Measured: 9 weeks
Secondary outcomes (4)
Systemic Vasodilator Response to Exercise
The effect of KNO3 on systemic vasodilator response, measured by change in systemic vascular resistance, during a symptom-limited maximal exercise test,
Measured: 9 weeks
Left Ventricle Diastolic Function
The effect of KNO3 on left ventricle diastolic filling parameters (measured with echocardiography at rest and after peak exercise)
Measured: 9 weeks
Myocardial Systolic Strain
The effect of KNO3 on myocardial strain (assessed with speckle-tracking echocardiography)
Measured: 9 weeks
Late Systolic Left Ventricle Load
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)
Measured: 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2018
- Study start1 May 2018
- Primary completion13 Mar 2019
- Study completion23 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Aortic Valve StenosisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- In this phase IIb, double-blind, cross-over trial, we will assign 22 subjects who are post-TAVR for severe AS to: (A) Potassium nitrate administered by mouth at a dose of 6 mEq three times daily for 4 weeks, or (B) Potassium chloride (KCl) at identical doses. The order of the interventions (AB-BA design) will be randomized, with a 1-week washout period separating each intervention. A crossover design will enable each subject to receive both treatments.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Julio Chirinos, MD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03483051
- Sponsor's protocol ID
- 828994
- Acronym
- PULSE-AS
- Status last verified
- Jun 2020
- First submitted
- 15 Feb 2018
- Last updated
- 17 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)
- ClinicalTrials.gov ID
- NCT03483051
- Acronym / sponsor ID
- PULSE-AS / 828994
- Conditions
- Aortic Valve Stenosis
- Keywords
- aortic stenosis, aortic valve replacement
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 May 2018 (actual)
- Primary completion
- 13 Mar 2019 (actual)
- Study completion
- 23 May 2019 (actual)
- First posted
- 29 Mar 2018 (actual)
- Results
- Posted 11 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- In this phase IIb, double-blind, cross-over trial, we will assign 22 subjects who are post-TAVR for severe AS to: (A) Potassium nitrate administered by mouth at a dose of 6 mEq three times daily for 4 weeks, or (B) Potassium chloride (KCl) at identical doses. The order of the interventions (AB-BA design) will be randomized, with a 1-week washout period separating each intervention. A crossover design will enable each subject to receive both treatments.
| Arm | Type | Receives |
|---|---|---|
| Potassium Nitrate (KNO3) | Experimental | Drug: Potassium NitrateCapsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks. |
| Potassium Chloride | Sham comparator | Drug: Potassium ChlorideCapsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Potassium NitratePotassium 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. | Drug | Potassium Nitrate (KNO3) |
| Potassium ChloridePotassium 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. | Drug | Potassium Chloride |
Primary outcome
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;
Peak Oxygen Uptake (VO2) During a Maximal Effort Exercise Test
Time frame: 9 weeks
The effect of KNO3 on exercise capacity, quantified as: Peak oxygen consumption (VO2) during a symptom-limited maximal effort exercise test.
Quality of Life Score
Time frame: 9 weeks
The effect of KNO3 on quality of life, assessed using the Kansas City Cardiomyopathy Questionnaire.
4 secondary outcomes
Systemic Vasodilator Response to Exercise
Time frame: 9 weeks
Left Ventricle Diastolic Function
Time frame: 9 weeks
Myocardial Systolic Strain
Time frame: 9 weeks
Late Systolic Left Ventricle Load
Time frame: 9 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Aortic Valve Stenosis
RecruitingObservational study
Spanish Prospective Registry of Hydra THV for Transcatheter Aortic Valve Implantation
Severe Aortic Valve Stenosis, Valvular Heart Disease
Active, not recruiting
Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients With Severe AS
Aortic Valve Stenosis, Hypertrophy, Left Ventricular
Not yet recruitingPhase 4
Application of TAVI at Experienced Interventional Cardiac Centers Without On-site Cardiac Surgery (ATLAS Study)
Aortic Stenosis, Severe Aortic Stenosis
Not yet recruiting
Exercise and Diet Supplements for Older Patients Undergoing TAVI: the IRON-TAVI Trial
Aortic Stenosis Disease, Aortic Stenosis Symptomatic
Active, not recruitingObservational study
REdo Transcatheter Aortic VALVE Implantation for the Management of Transcatheter Aortic Valve Failure
Aortic Valve Stenosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julio Chirinos, MD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Potassium Nitrate and Potassium Chloride in people with Aortic Valve Stenosis, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Work Performed During a Maximal-effort Exercise Test (time frame: 9 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2020; AzTrials last refreshed its copy on 30 Oct 2026.