Congestive Heart Failure
Conditions
Keywords
heart failure, diastolic dysfunction, systolic dysfunction, preclinical, natriuretic peptide, B-type natriuretic peptide, cyclic guanosine monophosphate
Brief summary
In congestive heart failure, cardiac output is low, blood pressure is high, and the body becomes congested with fluid. In normal people, when there is high blood pressure, the heart muscle cells secrete a hormone that excretes sodium and water in the urine, reducing blood pressure. The action of this hormone is called the natriuretic response. The purpose of this study is to determine if nesiritide can improve an impaired natriuretic response in subjects with asymptomatic systolic heart failure or asymptomatic diastolic heart failure.
Detailed description
The American Heart Association and the American College of Cardiology define stage B heart failure (HF) as asymptomatic subjects with abnormal heart structure/function. With the advancement of cardiac imaging and biomarkers, abnormal heart structure and function can be detected before the development of symptoms. Stage B HF can represent either diastolic or systolic dysfunction and both are at increased risk of adverse cardiac events and development of symptomatic HF. The broad objective of this study is to define the integrated cardiorenal response to acute volume expansion (VE) in humans with presystolic dysfunction (PSD), prediastolic dysfunction (PDD), and normal cardiac function. We hypothesized that there is an impaired cardiorenal endocrine response to acute VE in PSD and PDD which is characterized by the lack of appropriate activation of urinary cGMP and urinary sodium excretion. Further, we hypothesized that PSD, PDD, and normal control subjects would respond similarly to exogenous administration B-type natriuretic peptide (BNP). The natriuretic peptides (NPs) are a family of structurally similar but genetically distinct peptides with vasodilating, natriuretic, renin inhibiting, and lusitropic properties. Acute peptide therapy with brain natriuretic peptide (BNP) infusion has recently been approved by the FDA as a therapeutic strategy for the treatment of acute human decompensated congestive HF. We will determine the effects of acute subcutaneous BNP or placebo administration on the integrated cardiorenal and humoral response to acute sodium load (sodium chloride 0.9% 0.25 ml/kg/min for 1 hour) in three groups of subjects: Group 1 normal controls, Group 2 with PSD, and Group 3 with PDD. Doppler echocardiography and tonometry will be used to measure cardiac and vascular function before and during the sodium load. Renal function studies will assess sodium excretion, renal plasma flow, and glomerular filtration rate at baseline, during, and after the sodium load. Blood will be drawn for humoral analysis including catecholamines, renin, aldosterone, angiotensin II, atrial natriuretic peptide (ANP), BNP, and cyclic guanosine monophosphate (cGMP) at baseline, during, and after the sodium load.
Interventions
DRUGNesiritide
The first 10 subjects in each group will receive a dose of 5 ug/kg and the next ten subjects will receive 10 ug/kg.
DRUGPlacebo
The pharmacy created a placebo subcutaneous injection volume to match the volume of the nesiritide dose.
DRUGSaline
Normal saline 0.9% 0.25 ml/kg/min for 60 minutes
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
National Center for Research Resources (NCRR)
Horng Chen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
for normal control group: * ejection fraction of greater 50% * normal Doppler diastolic function with no clinical signs or symptoms * history of cardiovascular and renal disease * no prior use of any cardiovascular medications. Inclusion criteria for pre-systolic dysfunction group: * ejection fraction of less than 40% with no clinical signs or symptoms of congestive heart failure * ability to perform a 6-minute walk of \> 450 meters * if subjects are not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath, then they will still qualify for the study * subjects will all be on stable doses of ACE inhibitor for two weeks prior to the active study date * previously prescribed cardiovascular medications are allowed, however, all medications must be at stable doses two weeks prior to the study date. Inclusion criteria for pre-diastolic dysfunction group: * ejection fraction of greater than 50% with moderate or severe diastolic dysfunction as assessed by Doppler echocardiography * no signs or symptoms of congestive heart failure * ability to perform a 6-minute walk of \> 450 meters * if subjects are not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath, then they will still qualify for the study * previously prescribed cardiovascular medications are allowed, however, all medications must be at stable doses two weeks prior to the study date.
Exclusion criteria
for all groups: * myocardial infarction within 3 months of screening * unstable angina within 14 days of screening, or any evidence of myocardial ischemia * significant valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis * severe congenital heart diseases * sustained ventricular tachycardia or ventricular fibrillation within 14 days of screening * second or third degree heart block without a permanent cardiac pacemaker * stroke within 3 months of screening, or other evidence of significantly compromised CNS perfusion * total bilirubin of \> 1.5 mg/dL or other liver enzymes \>1.5 times the upper limit of normal * serum creatinine of \> 3.0 mg/dL * serum sodium of \< 125 mEq/dL or \> 160 mEq/dL * serum potassium of \< 3.5 mEq/dL or \> 5.0 mEq/dL * serum digoxin level of \> 2.0 ng/ml * systolic pressure of \< 85 mmHg * hemoglobin \< 10 gm/dl * other acute or chronic medical conditions or laboratory abnormality which may increase the risks associated with study participation or may interfere with interpretation of the data * received an investigational drug within 1 month prior to dosing * patients with an allergy to iodine * in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Baseline, 30 min, 60 min | Subjects received subcutaneous Nesiritide in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UcGMPV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE. |
| Change in Natriuresis (Urinary Sodium Excretion) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment | baseline and 60 minutes | Value at 60 minutes minus value at baseline. |
| Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Baseline, 30 min, 60 min | Subjects received subcutaneous placebo in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UNaV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE. |
| Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Baseline, 30 min, 60 min | Subjects received subcutaneous placebo in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UcGMPV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE. |
| Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Baseline, 30 min, 60 min | Subjects received subcutaneous Nesiritide in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UNaV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Cyclic Guanosine Monophosphate (cGMP) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment | baseline and 60 minutes | Value at 60 minutes minus value at baseline |
| Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 30 minutes | Value of natriuresis at 30 min on nesiritide treatment minus value of natriuresis at 30 min on placebo treatment (per subject group). The baseline was not involved in this calculation. |
| Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 60 minutes | Value of natriuresis at 60 min on nesiritide treatment minus value of natriuresis at 60 min on placebo treatment (per subject group). The baseline was not involved in this calculation. |
| Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 30 minutes | Value of cGMP at 30 min on nesiritide treatment minus value of cGMP at 30 min on placebo treatment (per subject group). The baseline was not involved in this calculation. |
| Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 60 minutes | Value of cGMP at 60 min on nesiritide treatment minus value of cGMP at 60 min on placebo treatment (per subject group). The baseline was not involved in this calculation. |
Countries
United States
Participant flow
Recruitment details
The study took place between February 2006 and August 2009. All subjects were consented and were seen at the Mayo Clinic in Rochester, MN.
Pre-assignment details
63 participants were enrolled in the study, but 5 participants were excluded because they did not meet inclusion criteria. Participants included normal controls, Preclinical Systolic Dysfunction, and Preclinical Diastolic Dysfunction subjects, who were randomized into Placebo First, then Nesiritide (Arm A) and Nesiritide First, then Placebo (Arm B)
Participants by arm
| Arm | Count |
|---|---|
| Control Group (Normals) Healthy volunteers without heart disease | 20 |
| Preclinical Systolic Dysfunction Group (PSD) Participants with ejection fraction \<40% and no heart failure symptoms | 20 |
| Preclinical Diastolic Dysfunction Group (PDD) Participants with an ejection fraction of \> 50% and no heart failure symptoms | 18 |
| Total | 58 |
Baseline characteristics
| Characteristic | Control Group (Normals) | Preclinical Systolic Dysfunction Group (PSD) | Preclinical Diastolic Dysfunction Group (PDD) | Total |
|---|---|---|---|---|
| Age Continuous | 37 years STANDARD_DEVIATION 11 | 65 years STANDARD_DEVIATION 12 | 72 years STANDARD_DEVIATION 7 | 57.5 years STANDARD_DEVIATION 18.4 |
| Blood Urea Nitrogen | 11 mg/dL STANDARD_DEVIATION 5 | 21 mg/dL STANDARD_DEVIATION 10 | 23 mg/dL STANDARD_DEVIATION 6 | 18.2 mg/dL STANDARD_DEVIATION 8.6 |
| Body Mass Index | 25 kg/m^2 STANDARD_DEVIATION 4 | 31 kg/m^2 STANDARD_DEVIATION 5 | 30 kg/m^2 STANDARD_DEVIATION 5 | 28.5 kg/m^2 STANDARD_DEVIATION 5.1 |
| Creatinine | 0.9 mg/dL STANDARD_DEVIATION 0.1 | 1.1 mg/dL STANDARD_DEVIATION 0.2 | 1.1 mg/dL STANDARD_DEVIATION 0.3 | 1.0 mg/dL STANDARD_DEVIATION 0.2 |
| Region of Enrollment United States | 20 participants | 20 participants | 18 participants | 58 participants |
| Sex: Female, Male Female | 17 Participants | 2 Participants | 9 Participants | 28 Participants |
| Sex: Female, Male Male | 3 Participants | 18 Participants | 9 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 58 | 6 / 58 |
| serious Total, serious adverse events | 0 / 58 | 1 / 58 |
Outcome results
Primary
Change in Natriuresis (Urinary Sodium Excretion) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment
Value at 60 minutes minus value at baseline.
Time frame: baseline and 60 minutes
Population: per protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Natriuresis (Urinary Sodium Excretion) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment | 87.19 mEq/min | Standard Error 22.26 |
p-value: <0.05t-test, 1 sided
Primary
Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV)
Subjects received subcutaneous Nesiritide in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UcGMPV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE.
Time frame: Baseline, 30 min, 60 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 399.6 pmol/min | Standard Deviation 252.6 |
| Control Group | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pretreatment) | 130.8 pmol/min | Standard Deviation 145.9 |
| Control Group | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 508.4 pmol/min | Standard Deviation 382.3 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 388.6 pmol/min | Standard Deviation 276.7 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pretreatment) | 192.2 pmol/min | Standard Deviation 157.3 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 518.7 pmol/min | Standard Deviation 578.3 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pretreatment) | 258.0 pmol/min | Standard Deviation 176.2 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 475.0 pmol/min | Standard Deviation 347.2 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 487.8 pmol/min | Standard Deviation 634 |
Primary
Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV)
Subjects received subcutaneous Nesiritide in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UNaV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE.
Time frame: Baseline, 30 min, 60 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 30 min | 393.4 uEq/min | Standard Deviation 143.4 |
| Control Group | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 183.9 uEq/min | Standard Deviation 58.1 |
| Control Group | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 60 min | 650.1 uEq/min | Standard Deviation 337.9 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 30 min | 314.7 uEq/min | Standard Deviation 225.3 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 232.6 uEq/min | Standard Deviation 166.7 |
| PSD-Preclinical Systolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 60 min | 469.4 uEq/min | Standard Deviation 458.9 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 219.1 uEq/min | Standard Deviation 201.7 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 60 min | 464.8 uEq/min | Standard Deviation 272.7 |
| PDD-Preclinical Diastolic Dysfunction | Nesiritide Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UNaV) | Urinary Sodium Excretion at 30 min | 303.2 uEq/min | Standard Deviation 185 |
Primary
Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV)
Subjects received subcutaneous placebo in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UcGMPV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE.
Time frame: Baseline, 30 min, 60 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 154.9 pmol/min | Standard Deviation 141.7 |
| Control Group | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pre-treatment) | 97.8 pmol/min | Standard Deviation 124.8 |
| Control Group | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 196.0 pmol/min | Standard Deviation 182.6 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 133.3 pmol/min | Standard Deviation 109.9 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pre-treatment) | 219.5 pmol/min | Standard Deviation 188.1 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 134.1 pmol/min | Standard Deviation 97.7 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion (Baseline/Pre-treatment) | 245.8 pmol/min | Standard Deviation 198.7 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 60 min | 139.7 pmol/min | Standard Deviation 118.6 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary cGMP Excretion After Volume Expansion (UcGMPV) | Urinary cGMP Excretion at 30 min | 134.4 pmol/min | Standard Deviation 114.4 |
Primary
Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV)
Subjects received subcutaneous placebo in the abdomen. After 15 minutes, the acute saline load (volume expansion, VE) was administered. Subjects were asked to empty bladder spontaneously every 30 min (if unable to void every 30 min, a urinary catheter was placed). Adequate bladder emptying was insured by ultrasonography. UNaV was collected at baseline (immediately before VE) and at 30 and 60 min after initiation of VE.
Time frame: Baseline, 30 min, 60 min
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control Group | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 30 min | 197.4 uEq/min | Standard Deviation 80.8 |
| Control Group | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 186.6 uEq/min | Standard Deviation 67.3 |
| Control Group | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 60 min | 211.8 uEq/min | Standard Deviation 89.5 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 30 min | 221.0 uEq/min | Standard Deviation 118.6 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 255.4 uEq/min | Standard Deviation 189.2 |
| PSD-Preclinical Systolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 60 min | 231.1 uEq/min | Standard Deviation 130.8 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion (Baseline/Pre-treatment) | 202.1 uEq/min | Standard Deviation 137.5 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 60 min | 205.0 uEq/min | Standard Deviation 130.5 |
| PDD-Preclinical Diastolic Dysfunction | Placebo Pre-Treatment Urinary Sodium Excretion After Volume Expansion (UnaV) | Urinary Sodium Excretion at 30 min | 187.9 uEq/min | Standard Deviation 110.3 |
Secondary
Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment
Value of natriuresis at 30 min on nesiritide treatment minus value of natriuresis at 30 min on placebo treatment (per subject group). The baseline was not involved in this calculation.
Time frame: 30 minutes
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 440.93 mEq/min | Standard Error 76.67 |
| PSD-Preclinical Systolic Dysfunction | Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 261.07 mEq/min | Standard Error 101.6 |
| PDD-Preclinical Diastolic Dysfunction | Change in Natriuresis (Urinary Sodium Excretion) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 242.82 mEq/min | Standard Error 68.58 |
Secondary
Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment
Value of natriuresis at 60 min on nesiritide treatment minus value of natriuresis at 60 min on placebo treatment (per subject group). The baseline was not involved in this calculation.
Time frame: 60 minutes
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 183.83 mEq/min | Standard Error 60.6 |
| PSD-Preclinical Systolic Dysfunction | Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 226.89 mEq/min | Standard Error 101.72 |
| PDD-Preclinical Diastolic Dysfunction | Change in Natriuresis (Urinary Sodium Excretion) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 41.55 mEq/min | Standard Error 46.07 |
Secondary
Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment
Value of cGMP at 30 min on nesiritide treatment minus value of cGMP at 30 min on placebo treatment (per subject group). The baseline was not involved in this calculation.
Time frame: 30 minutes
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 244.69 pmol/min | Standard Error 59.09 |
| PSD-Preclinical Systolic Dysfunction | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 255.31 pmol/min | Standard Error 59.6 |
| PDD-Preclinical Diastolic Dysfunction | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 30 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 353.37 pmol/min | Standard Error 155.65 |
Secondary
Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment
Value of cGMP at 60 min on nesiritide treatment minus value of cGMP at 60 min on placebo treatment (per subject group). The baseline was not involved in this calculation.
Time frame: 60 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 303.32 pmol/min | Standard Error 71.21 |
| PSD-Preclinical Systolic Dysfunction | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 384.62 pmol/min | Standard Error 120.47 |
| PDD-Preclinical Diastolic Dysfunction | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) at 60 Minutes in Response to Nesiritide Treatment Compared to Placebo Treatment | 335.29 pmol/min | Standard Error 90.48 |
Secondary
Change in Urinary Cyclic Guanosine Monophosphate (cGMP) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment
Value at 60 minutes minus value at baseline
Time frame: baseline and 60 minutes
Population: intention to treat (ITT)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Group | Change in Urinary Cyclic Guanosine Monophosphate (cGMP) in Control Subjects at 60 Minutes After Volume Expansion Compared to Baseline in Response to Placebo Treatment | 98.23 pmol/min | Standard Error 34.12 |
p-value: <0.05rank-sum test