Trial Outcomes & Findings for Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure (NCT NCT00252187)
NCT ID: NCT00252187
Last Updated: 2012-12-20
Results Overview
LV volume was measured for systolic volume and diastolic volume using a cardiac Magnetic Resonance Imaging (MRI) scan. All cardiac MRI images were reviewed by an independent cardiologist in a blinded fashion.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
45 participants
Primary outcome timeframe
Baseline and 8 weeks
Results posted on
2012-12-20
Participant Flow
Participants were recruited from May 2003 to May 2008 at the Mayo Clinic in Rochester, Minnesota.
Participant milestones
| Measure |
B-type Natriuretic Peptide (BNP)
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
24
|
21
|
|
Overall Study
COMPLETED
|
20
|
20
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
B-type Natriuretic Peptide (BNP)
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Cardiac Hormone Replacement With Brain Natriuretic Peptide (BNP) in Heart Failure
Baseline characteristics by cohort
| Measure |
B-type Natriuretic Peptide (BNP)
n=24 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=21 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
Total
n=45 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
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Age Continuous
|
66 years
STANDARD_DEVIATION 10 • n=5 Participants
|
65 years
STANDARD_DEVIATION 11 • n=7 Participants
|
66 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
33 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
21 participants
n=7 Participants
|
45 participants
n=5 Participants
|
|
Blood pressure
Systolic blood pressure
|
131 mmHg
STANDARD_DEVIATION 18 • n=5 Participants
|
127 mmHg
STANDARD_DEVIATION 17 • n=7 Participants
|
129 mmHg
STANDARD_DEVIATION 17 • n=5 Participants
|
|
Blood pressure
Diastolic blood pressure
|
72 mmHg
STANDARD_DEVIATION 11 • n=5 Participants
|
72 mmHg
STANDARD_DEVIATION 14 • n=7 Participants
|
72 mmHg
STANDARD_DEVIATION 12 • n=5 Participants
|
|
New York Heart Association (NYHA) CHF Classification
NYHA CHF Class II
|
13 participants
n=5 Participants
|
10 participants
n=7 Participants
|
23 participants
n=5 Participants
|
|
New York Heart Association (NYHA) CHF Classification
NYHA CHF Class III
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Left Ventricle Ejection Fraction (Echo)
|
32 Percentage
STANDARD_DEVIATION 9 • n=5 Participants
|
31 Percentage
STANDARD_DEVIATION 7 • n=7 Participants
|
31 Percentage
STANDARD_DEVIATION 8 • n=5 Participants
|
|
Heart Rate
|
65 beats per minute
STANDARD_DEVIATION 13 • n=5 Participants
|
68 beats per minute
STANDARD_DEVIATION 12 • n=7 Participants
|
67 beats per minute
STANDARD_DEVIATION 13 • n=5 Participants
|
|
Plasma BNP
|
51 picograms/milliliter
n=5 Participants
|
63 picograms/milliliter
n=7 Participants
|
53 picograms/milliliter
n=5 Participants
|
|
Glomerular Filtration Rate
|
73 ml/min/1.73 m^2
STANDARD_DEVIATION 22 • n=5 Participants
|
77 ml/min/1.73 m^2
STANDARD_DEVIATION 21 • n=7 Participants
|
75 ml/min/1.73 m^2
STANDARD_DEVIATION 22 • n=5 Participants
|
|
History or concomitant medical conditions
History of peripheral vascular diseases
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of chronic obstructive pulmonary disease
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of Coronary Artery Disease
|
11 participants
n=5 Participants
|
11 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of hypertension
|
10 participants
n=5 Participants
|
17 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of arrythmia
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of smoking
|
10 participants
n=5 Participants
|
8 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of diabetes
|
11 participants
n=5 Participants
|
7 participants
n=7 Participants
|
18 participants
n=5 Participants
|
|
History or concomitant medical conditions
History of high cholesterol
|
15 participants
n=5 Participants
|
17 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Concomitant Medication(s)
ACE I inhib, Angio II receptor blocker or nitrates
|
23 participants
n=5 Participants
|
20 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
Concomitant Medication(s)
Digoxin
|
8 participants
n=5 Participants
|
9 participants
n=7 Participants
|
17 participants
n=5 Participants
|
|
Concomitant Medication(s)
Beta blocker
|
23 participants
n=5 Participants
|
20 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
Concomitant Medication(s)
Coumadin
|
3 participants
n=5 Participants
|
1 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Concomitant Medication(s)
Antiarrhythmics
|
5 participants
n=5 Participants
|
0 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Concomitant Medication(s)
Diuretic (loop)
|
18 participants
n=5 Participants
|
15 participants
n=7 Participants
|
33 participants
n=5 Participants
|
|
Concomitant Medication(s)
Diuretic (thiazide)
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Concomitant Medication(s)
Diuretic (potassium sparing)
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Concomitant Medication(s)
Diuretic (Thiazide)
|
4 participants
n=5 Participants
|
3 participants
n=7 Participants
|
7 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
LV volume was measured for systolic volume and diastolic volume using a cardiac Magnetic Resonance Imaging (MRI) scan. All cardiac MRI images were reviewed by an independent cardiologist in a blinded fashion.
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Left Ventricular (LV) Volume Index at 8 Weeks
End-systolic LV volume index
|
-5.2 ml/m^2
Standard Deviation 13
|
5.8 ml/m^2
Standard Deviation 9.6
|
|
Change in Left Ventricular (LV) Volume Index at 8 Weeks
End-diastolic LV volume index
|
-10.0 ml/m^2
Standard Deviation 15.4
|
6.1 ml/m^2
Standard Deviation 12.4
|
PRIMARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Left Ventricular (LV) Mass Index at 8 Weeks
|
-4.4 mg/m^2
Standard Deviation 9.8
|
6.2 mg/m^2
Standard Deviation 12.9
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Filling pressure determined by ratio of E/e' \[Echocardiograph Doppler mitral inflow velocity (E) to mitral annulus tissue Doppler velocity (e') ratio\]
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Left Ventricular (LV) Filling Pressure at 8 Weeks
|
-2.3 E/e'
Standard Deviation 2.5
|
1.1 E/e'
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Plasma renin is synthesized within circulation or at tissue sites, causing vasoconstriction or vasodilation.
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Plasma Renin Activity at 8 Weeks
|
-3.5 nanograms per milliliter per hour
Standard Deviation 7.1
|
2.3 nanograms per milliliter per hour
Standard Deviation 4.8
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Kidney function was measured by GFR determined by iothalamate clearance. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m\^2 of body-surface area. A lower GFR means the kidney is not filtering normally.
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Renal Function as Measured by Glomerular Filtration Rate (GFR) at 8 Weeks
|
6.9 ml/min/1.73 m^2 of body-surface area
Standard Deviation 14.2
|
-2.8 ml/min/1.73 m^2 of body-surface area
Standard Deviation 24.8
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Heart rate was measured when MRI was performed
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Heart Rate at 8 Weeks
|
-1.6 beats per minute
Standard Deviation 8.3
|
-0.9 beats per minute
Standard Deviation 7.2
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Blood pressure was measured during the MRI
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Blood Pressure at 8 Weeks
Change in systolic blood pressure
|
-4.9 mmHg
Standard Deviation 22.2
|
4.5 mmHg
Standard Deviation 17.7
|
|
Change in Blood Pressure at 8 Weeks
Change in diastolic blood pressure
|
-2.4 mmHg
Standard Deviation 8.5
|
0.9 mmHg
Standard Deviation 12.1
|
SECONDARY outcome
Timeframe: Baseline and 8 weeksPopulation: Per protocol population
Left Ventricle Ejection Fraction (LVEF)is a clinical parameter used by cardiologists to describe how well the heart is pumping. LVEF is a measure of the amount of blood pumped out of the lower chamber (ventricle) of the heart during a heartbeat, measured by Magnetic Resonance Imaging (MRI).
Outcome measures
| Measure |
B-type Natriuretic Peptide (BNP)
n=20 Participants
BNP (nesiritide) hormone self-administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=20 Participants
Placebo self-administered subcutaneously twice daily for 8 weeks.
|
|---|---|---|
|
Change in Left Ventricular Ejection Fraction at 8 Weeks
|
0.0 percentage
Standard Deviation 7.5
|
-1.1 percentage
Standard Deviation 4.2
|
Adverse Events
BPN Group
Serious events: 3 serious events
Other events: 20 other events
Deaths: 0 deaths
Placebo
Serious events: 1 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BPN Group
n=24 participants at risk
BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=21 participants at risk
Placebo self-administered subcutaneously twice daily for 8 weeks
|
|---|---|---|
|
Cardiac disorders
hypotension
|
4.2%
1/24 • Number of events 1 • Adverse events were collected over the 8 week study period
|
0.00%
0/21 • Adverse events were collected over the 8 week study period
|
|
Cardiac disorders
lightheadedness
|
4.2%
1/24 • Number of events 2 • Adverse events were collected over the 8 week study period
|
0.00%
0/21 • Adverse events were collected over the 8 week study period
|
|
Eye disorders
visual disturbances
|
4.2%
1/24 • Number of events 1 • Adverse events were collected over the 8 week study period
|
0.00%
0/21 • Adverse events were collected over the 8 week study period
|
|
Cardiac disorders
worsening heart failure symptoms
|
0.00%
0/24 • Adverse events were collected over the 8 week study period
|
4.8%
1/21 • Number of events 1 • Adverse events were collected over the 8 week study period
|
Other adverse events
| Measure |
BPN Group
n=24 participants at risk
BNP (nesiritide) administered subcutaneously twice daily for 8 weeks at 10 mcg/kg.
|
Placebo
n=21 participants at risk
Placebo self-administered subcutaneously twice daily for 8 weeks
|
|---|---|---|
|
Cardiac disorders
Lightheadedness
|
15.0%
3/20 • Number of events 3 • Adverse events were collected over the 8 week study period
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
|
Cardiac disorders
Shortness of Breath and Fatigue
|
15.0%
3/20 • Number of events 3 • Adverse events were collected over the 8 week study period
|
35.0%
7/20 • Number of events 7 • Adverse events were collected over the 8 week study period
|
|
Skin and subcutaneous tissue disorders
Injection site sting/itchy
|
20.0%
4/20 • Number of events 4 • Adverse events were collected over the 8 week study period
|
15.0%
3/20 • Number of events 3 • Adverse events were collected over the 8 week study period
|
|
General disorders
Flu-like symptoms
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
10.0%
2/20 • Number of events 2 • Adverse events were collected over the 8 week study period
|
|
Blood and lymphatic system disorders
Flushing
|
15.0%
3/20 • Number of events 3 • Adverse events were collected over the 8 week study period
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
|
Gastrointestinal disorders
Loose stools
|
10.0%
2/20 • Number of events 2 • Adverse events were collected over the 8 week study period
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
|
Cardiac disorders
Atrial Fibrillation
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
|
Blood and lymphatic system disorders
Edema
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
|
Gastrointestinal disorders
GI bleed prior to study drug administration
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
|
Renal and urinary disorders
Increased voiding
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
|
Hepatobiliary disorders
Choledocholithiasis
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
|
Infections and infestations
Head congestion and productive cough
|
0.00%
0/20 • Adverse events were collected over the 8 week study period
|
5.0%
1/20 • Number of events 1 • Adverse events were collected over the 8 week study period
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place