Trial Outcomes & Findings for Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS) (NCT NCT03483051)

NCT ID: NCT03483051

Last Updated: 2020-06-17

Results Overview

The effect of KNO3 on exercise capacity, quantified as Total work performed during a maximal-effort exercise test;

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

9 weeks

Results posted on

2020-06-17

Participant Flow

1 subject withdrew consent prior to treatment 1 subject screen failed

Participant milestones

Participant milestones
Measure	ARM A Potassium Nitrate Then Potassium Chloride Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Nitrate: 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.	ARM B Potassium Chloride Then Potassium Nitrate Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Chloride: 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.
First Treatment, Pre Crossover STARTED	2	1
First Treatment, Pre Crossover COMPLETED	2	1
First Treatment, Pre Crossover NOT COMPLETED	0	0
Second Treatment, After Crossover STARTED	2	1
Second Treatment, After Crossover COMPLETED	2	1
Second Treatment, After Crossover NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Targeting Pulsatile Load to Increase Exercise Capacity and Quality of Life After Aortic Valve Replacement for Severe Aortic Stenosis (PULSE AS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ARM A Potassium Nitrate Then Potassium Chloride n=2 Participants Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Nitrate: 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.	ARM B Potassium Chloride Then Potassium Nitrate n=1 Participants Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Chloride: 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.	Total n=3 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on exercise capacity, quantified as Total work performed during a maximal-effort exercise test;

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on exercise capacity, quantified as: Peak oxygen consumption (VO2) during a symptom-limited maximal effort exercise test.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on quality of life, assessed using the Kansas City Cardiomyopathy Questionnaire.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on systemic vasodilator response, measured by change in systemic vascular resistance, during a symptom-limited maximal exercise test,

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on left ventricle diastolic filling parameters (measured with echocardiography at rest and after peak exercise)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

The effect of KNO3 on myocardial strain (assessed with speckle-tracking echocardiography)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 9 weeks

Population: Efficacy data analyses cannot be reported for privacy reasons due to enrollment of only three (3) subjects.

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)

Outcome measures

Outcome data not reported

Adverse Events

ARM A Potassium Nitrate Then Potassium Chloride

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

ARM B Potassium Chloride Then Potassium Nitrate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	ARM A Potassium Nitrate Then Potassium Chloride n=2 participants at risk Capsules containing 18 mmoles of KNO3 per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Nitrate: 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.	ARM B Potassium Chloride Then Potassium Nitrate n=1 participants at risk Capsules containing 18 mmoles of KCl per day, given as one capsule (6 mmoles) three times a day for 4 weeks. Potassium Chloride: 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.
Cardiac disorders Lightheadedness	100.0% 2/2 • Number of events 2 • 1 Year	0.00% 0/1 • 1 Year
Gastrointestinal disorders Stomach Ache, diarrhea, nausea or vomiting	50.0% 1/2 • Number of events 1 • 1 Year	0.00% 0/1 • 1 Year
Vascular disorders Drop in blood pressure when standing up	50.0% 1/2 • Number of events 1 • 1 Year	0.00% 0/1 • 1 Year

Additional Information

Dr. Julio Chirinos

University of Pennsylvania

Phone: 215-200-7779

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place