Trial Outcomes & Findings for Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF (NCT NCT02256345)
NCT ID: NCT02256345
Last Updated: 2017-10-03
Results Overview
Peak oxygen uptake (VO2) defined as the average value obtained during the last 30 seconds of exercise.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
12 participants
Primary outcome timeframe
Baseline, end of week 1, end of week 2
Results posted on
2017-10-03
Participant Flow
Participant milestones
| Measure |
Randomized to KNO3
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated.
Active Comparator: Potassium Nitrate (KNO3)
|
Randomized to KCl
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated.
Placebo Comparator: Potassium Chloride (KCl)
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
3
|
|
Overall Study
COMPLETED
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics, Pharmacodynamics, and Impact of Inorganic Nitrate on Exercise in HFpEF
Baseline characteristics by cohort
| Measure |
Randomized to KNO3
n=9 Participants
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 Participants
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
Total
n=12 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.4 years
STANDARD_DEVIATION 5.5 • n=5 Participants
|
62.7 years
STANDARD_DEVIATION 8.0 • n=7 Participants
|
62.5 years
STANDARD_DEVIATION 5.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, n (%) · White
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, n (%) · Black
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, n (%) · Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
New York Heart Association Heart failure classification (NYHA Class) n (%)
Class II
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
New York Heart Association Heart failure classification (NYHA Class) n (%)
Class III
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Body Mass Index, kg/m^2, mean (SD)
|
33.4 kg/m^2
STANDARD_DEVIATION 6.3 • n=5 Participants
|
37.4 kg/m^2
STANDARD_DEVIATION 9.9 • n=7 Participants
|
34.4 kg/m^2
STANDARD_DEVIATION 7.0 • n=5 Participants
|
|
Number of Obese Participants, n(%)
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Number of Hypertensive Participants, n(%)
|
9 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Number of Participants with Hyperlipidemia, n (%)
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Number of Participants with Coronary Artery Disease, n (%)
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Number of Participants with History of atrial fibrillation, n (%)
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Number of Participants with Diabetes Mellitus, n (%)
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Number of Participants with Obstructive sleep apnea, n (%)
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Number of Participants with Current Continuous Positive Airway Pressure (CPAP) use, n (%)
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Number of Participants with Obstructive lung disease, n (%)
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Number of Participants on Beta-blockers, n (%)
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Number of Participants onACEI/ARB, n (%)
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Number of Participants on Mineralocorticoid receptor antagonists, n (%)
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Number of Participants on Calcium-channel blockers, n (%)
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Number of Participants on Loop diuretics, n (%)
|
7 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Number of Participants on Thiazide diuretic, n (%)
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Number of Participants on Statin, n (%)
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR), mL/min per 1.73m^2, mean (SD)
|
71.0 mL/min per 1.73m^2
STANDARD_DEVIATION 14.1 • n=5 Participants
|
64.7 mL/min per 1.73m^2
STANDARD_DEVIATION 5.9 • n=7 Participants
|
69.4 mL/min per 1.73m^2
STANDARD_DEVIATION 12.6 • n=5 Participants
|
|
Estimated Glomerular Filtration Rate (eGFR) <60 mL/min per 1.73m^2, n (%)
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
N-terminal pro-brain natriuretic peptide (NT-proBNP), pg/ml, mean (SD)
|
108.3 pg/ml
STANDARD_DEVIATION 94.7 • n=5 Participants
|
119 pg/ml
STANDARD_DEVIATION 87.0 • n=7 Participants
|
111 pg/ml
STANDARD_DEVIATION 89.0 • n=5 Participants
|
|
Number of Participants with high N-terminal pro-brain natriuretic peptide (NT-proBNP), pg/ml, n (%)
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Hemoglobin, g/dL, mean (SD)
|
13.6 g/dL
STANDARD_DEVIATION 0.8 • n=5 Participants
|
13.5 g/dL
STANDARD_DEVIATION 1.0 • n=7 Participants
|
13.6 g/dL
STANDARD_DEVIATION 0.8 • n=5 Participants
|
|
Methemoglobin, %, mean (SD)
|
1.0 percent of total hemoglobin
STANDARD_DEVIATION 0.2 • n=5 Participants
|
1.0 percent of total hemoglobin
STANDARD_DEVIATION 0.5 • n=7 Participants
|
1.0 percent of total hemoglobin
STANDARD_DEVIATION 0.3 • n=5 Participants
|
|
Left Ventricular (LV) mass,g, mean (SD)
|
174.43 g
STANDARD_DEVIATION 77.09 • n=5 Participants
|
165.98 g
STANDARD_DEVIATION 19.27 • n=7 Participants
|
172.32 g
STANDARD_DEVIATION 66.36 • n=5 Participants
|
|
Left Ventricular (LV) mass index, g/m^2, mean (SD)
|
79.78 g/m^2
STANDARD_DEVIATION 26.01 • n=5 Participants
|
76.18 g/m^2
STANDARD_DEVIATION 7.33 • n=7 Participants
|
78.88 g/m^2
STANDARD_DEVIATION 22.46 • n=5 Participants
|
|
Relative wall thickness, mean (SD)
|
0.47 ratio
STANDARD_DEVIATION 0.09 • n=5 Participants
|
0.46 ratio
STANDARD_DEVIATION 0.09 • n=7 Participants
|
0.47 ratio
STANDARD_DEVIATION 0.09 • n=5 Participants
|
|
Mitral early inflow velocity (E), cm/s, mean (SD)
|
74.53 cm/s
STANDARD_DEVIATION 24.75 • n=5 Participants
|
85.73 cm/s
STANDARD_DEVIATION 7.04 • n=7 Participants
|
77.33 cm/s
STANDARD_DEVIATION 21.91 • n=5 Participants
|
|
Mitral atrial inflow velocity (E), cm/s, mean (SD)
|
70.74 cm/s
STANDARD_DEVIATION 20.06 • n=5 Participants
|
88.61 cm/s
STANDARD_DEVIATION 21.28 • n=7 Participants
|
75.21 cm/s
STANDARD_DEVIATION 20.99 • n=5 Participants
|
|
Septal tissue doppler early velocity (e'), mm/s, mean (SD)
|
70.64 mm/s
STANDARD_DEVIATION 12.45 • n=5 Participants
|
93.71 mm/s
STANDARD_DEVIATION 28.65 • n=7 Participants
|
76.41 mm/s
STANDARD_DEVIATION 19.26 • n=5 Participants
|
|
Septal E/e' ratio, mean (SD)
|
10.70 ratio
STANDARD_DEVIATION 3.76 • n=5 Participants
|
9.60 ratio
STANDARD_DEVIATION 2.39 • n=7 Participants
|
10.42 ratio
STANDARD_DEVIATION 3.40 • n=5 Participants
|
|
Left atrial volume index, mL/m^2, mean (SD)
|
27.20 mL/m^2
STANDARD_DEVIATION 7.87 • n=5 Participants
|
29.38 mL/m^2
STANDARD_DEVIATION 5.33 • n=7 Participants
|
27.74 mL/m^2
STANDARD_DEVIATION 7.15 • n=5 Participants
|
|
Left ventricular ejection fraction, %, mean (SD)
|
65.84 % (stroke volume/ end-diastolic vol)x100
STANDARD_DEVIATION 7.74 • n=5 Participants
|
59.41 % (stroke volume/ end-diastolic vol)x100
STANDARD_DEVIATION 13.66 • n=7 Participants
|
64.23 % (stroke volume/ end-diastolic vol)x100
STANDARD_DEVIATION 9.27 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, end of week 1, end of week 2Peak oxygen uptake (VO2) defined as the average value obtained during the last 30 seconds of exercise.
Outcome measures
| Measure |
Randomized to KNO3
n=9 Participants
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 Participants
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
|---|---|---|
|
Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose
Baseline Viist
|
1.16 L/min
Interval 1.13 to 1.19
|
1.49 L/min
Interval 1.43 to 1.54
|
|
Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose
End of week 1 visit
|
1.20 L/min
Interval 1.17 to 1.24
|
1.44 L/min
Interval 1.39 to 1.49
|
|
Change in Peak Oxygen Uptake (VO2) From Baseline Upto 1 Week of Administration for Each Dose
End of week 2 visit
|
1.20 L/min
Interval 1.17 to 1.23
|
1.44 L/min
Interval 1.39 to 1.5
|
SECONDARY outcome
Timeframe: Baseline, end of week 1, end of week 2Percent change in peak vascular resistance from rest to peak exercise
Outcome measures
| Measure |
Randomized to KNO3
n=9 Participants
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 Participants
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
|---|---|---|
|
Change in Vasodilatory Reserve for Each Dose
Baseline
|
-25.6 %change in peak vascular resistance
Interval -40.9 to -10.4
|
-25.8 %change in peak vascular resistance
Interval -31.4 to -20.3
|
|
Change in Vasodilatory Reserve for Each Dose
End of week 1 visit
|
-27.1 %change in peak vascular resistance
Interval -43.6 to -10.5
|
-30.6 %change in peak vascular resistance
Interval -36.2 to -25.1
|
|
Change in Vasodilatory Reserve for Each Dose
End of week 2 visit
|
-34.2 %change in peak vascular resistance
Interval -49.4 to -18.9
|
-20.0 %change in peak vascular resistance
Interval -24.2 to -15.8
|
SECONDARY outcome
Timeframe: Baseline, end of week 1, end of week 2Percent change in oxidative capacity (oxyhemoglobin levels) before and after occlusion
Outcome measures
| Measure |
Randomized to KNO3
n=9 Participants
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 Participants
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
|---|---|---|
|
Change in Mitochondrial Oxidative Capacity for Each Dose
End of week 1 visit
|
59.2 Percent change in oxidative capacity
Interval 42.1 to 76.2
|
110.4 Percent change in oxidative capacity
Interval 63.2 to 157.7
|
|
Change in Mitochondrial Oxidative Capacity for Each Dose
Baseline
|
63.2 Percent change in oxidative capacity
Interval 47.6 to 78.8
|
106.5 Percent change in oxidative capacity
Interval 59.2 to 153.7
|
|
Change in Mitochondrial Oxidative Capacity for Each Dose
End of Week 2 visit
|
62.2 Percent change in oxidative capacity
Interval 46.6 to 77.7
|
45.4 Percent change in oxidative capacity
Interval 5.0 to 85.8
|
SECONDARY outcome
Timeframe: Baseline, end of week 1, end of week 2Percent change in augmentation index, whereas augmentation index at each time point (visit) is defined as the amplitude of the second peak to the first peak of the aortic pulse wave form multiplied by 100: augmentation index = (P2/P1)×100.
Outcome measures
| Measure |
Randomized to KNO3
n=9 Participants
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 Participants
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
|---|---|---|
|
Change in Aortic Augmentation Index
Baseline visit
|
3.0 Percent change in augumentation index
Interval -5.4 to 11.4
|
-2.3 Percent change in augumentation index
Interval -11.5 to 6.8
|
|
Change in Aortic Augmentation Index
End of week 1 visit
|
-5.4 Percent change in augumentation index
Interval -13.1 to 2.4
|
-11.9 Percent change in augumentation index
Interval -23.5 to -0.2
|
|
Change in Aortic Augmentation Index
End of week 2 visit
|
-7.1 Percent change in augumentation index
Interval -14.9 to 0.6
|
-0.2 Percent change in augumentation index
Interval -9.4 to 9.0
|
Adverse Events
Randomized to KNO3
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Randomized to KCl
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Randomized to KNO3
n=9 participants at risk
KNO3 will be given at a dose of 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if well tolerated
Active Comparator: Potassium Nitrate
|
Randomized to KCl
n=3 participants at risk
KCl will be used as a placebo and will be given as 6 mmol twice daily for the first week, increasing to 6 mmol three times daily for the second week if tolerating well.
Placebo Comparator: Potassium Chloride
|
|---|---|---|
|
General disorders
Any side effect
|
44.4%
4/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
33.3%
1/3 • Number of events 1 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
Gastrointestinal disorders
GI symptoms
|
33.3%
3/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
33.3%
1/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
0.00%
0/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
Cardiac disorders
Palpitations
|
11.1%
1/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
0.00%
0/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
Cardiac disorders
Mild lower extremity edema
|
0.00%
0/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
33.3%
1/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
Infections and infestations
Tooth infection
|
11.1%
1/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
0.00%
0/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
|
General disorders
Fatigue
|
11.1%
1/9 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
0.00%
0/3 • Adverse events were collected at every visit. There are a total of three visits that are 1 week apart.
All adverse events were non serious so they are reported under Other Adverse Events
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place