The purpose of this exploratory study is to assess the efficacy and safety of nesiritide in participants with acute (a quick and severe form of illness in its early stage) heart failure (when the heart inadequately pumps blood through the body) including acute exacerbation of chronic (lasting a long time) heart failure, administered intravenous (into a vein) bolus (a large amount) followed by intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle).
This is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), multi-center (when more than 1 hospital or medical school team work on a medical research study), randomized (study medication assigned by chance), stepwise, bolus plus intravenous infusion, fixed-flexible (arbitrary dose titration \[slow increase in drug dosage, guided by participant's responses\]) study. The study consists of 3 periods: Observation period (from the time of obtaining consent to the start of study treatment), Treatment period, and Follow-up period (from 24 hours after the initiation of study treatment \[discontinuation\] to 30 days after the initiation of study treatment). The participants will be randomly assigned to 1 of the following 3 treatment groups: 2+0.005 group, 1+0.01 group and 2+0.01 group. The treatment period consists of treatment with bolus injection (over 1 minute) followed by intravenous infusion (over 24 hours: Period 1 \[fixed-dose period\] of 3 hours and Period 2 \[flexible-dose period\] of 21 hours).The study will be conducted stepwise and hence, initially participants will be randomly assigned to 1 of the following 2 groups: 1+0.01 group and 2+0.005 group. Participants will receive nesiritide at an initial dose of 0.005 or 0.01 microgram per kilogram per minute (mcg/kg/min), and the dose escalation of 0.005 mcg/kg/min per dose will be conducted every 3 hours up to maximum of 0.03 mcg/kg/min in Period 2. Safety data of at least 5 participants will be assessed for each group, and after confirming the safety of 2 groups, the participants will be assigned to third group of nesiritide 2 microgram per kilogram (mcg/kg) +0.01 mcg/kg/min. Then participants will be followed up to a maximum of 30 days after the initiation of study treatment, in follow-up period. Participants will primarily be evaluated for the effect of nesiritide on hemodynamic parameters such as pulmonary capillary wedge pressure (PCWP), or if it is unmeasurable then it will be complemented with pulmonary arterial diastolic pressure (PADP). Participants' safety will also be monitored throughout the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
67
Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 1 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 15.4 to 35.2 mcg/kg.
Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (fixed-dose) with dose of 0.005 mcg/kg/min and Period 2 (flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 9.2 to 31.7 mcg/kg.
Unnamed facility
Amagasaki, Japan
Unnamed facility
Chikushino-shi, Japan
Unnamed facility
Hiroshima, Japan
Unnamed facility
Ikoma, Japan
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP or Pulmonary Arterial Diastolic Pressure[PADP]) at 3 Hours
Change in PCWP was unmeasurable, therefore it was complemented with PADP. PCWP was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
Time frame: Baseline and 3 Hours
Change From Baseline in Mean Right Atrial Pressure (MRAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour
The MRAP was a measured hemodynamic parameter. MRAP was measured using a Swan-Ganz catheter.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour
Change From Baseline in Pulmonary Arterial Systolic Pressure (PASP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The PASP was a measured hemodynamic parameters. PASP was assessed by Swan-Ganz catheter.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Pulmonary Arterial Diastolic Pressure (PADP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The PADP was a measured hemodynamic parameter. Normal range of PADP is 8 to 15 millimeters of mercury (mmHg). PADP was assessed by Swan-Ganz catheter.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Mean Pulmonary Arterial Pressure (MPAP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The MPAP was a measured hemodynamic parameter. MPAP was measured using a Swan-Ganz catheter.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Intravenous bolus treatment will be administered over 1 minute (min) at a dose of 2 microgram per kilogram (mcg/kg) followed by 24 hour intravenous infusion which is comprised of Period 1 (Fixed-dose) with dose of 0.01 mcg/kg/min and Period 2 (Flexible-dose) where dosage will be increased by 0.005 mcg/kg/min every 3 hours. Total dosage to be administered will be 16.4 to 36.2 mcg/kg.
Unnamed facility
Komatsushima, Japan
Unnamed facility
Kumamoto, Japan
Unnamed facility
Moriyama, Japan
Unnamed facility
Osaka, Japan
Unnamed facility
Saitama, Japan
Unnamed facility
Tokyo, Japan
...and 1 more locations
The PCWP was a measured hemodynamic parameter. It was the blood pressure, recorded after wedging a catheter in a small pulmonary artery; believed to reflect the pressure in the pulmonary capillaries. It was measured by pulmonary artery catheterization and provided an indirect measure of left atrial pressure.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Cardiac Output (CO) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The CO was a measured cardiopulmonary hemodynamic parameter. It is the volume of blood expelled by the ventricles of the heart with each beat. It was calculated as the product of stroke volume (output of either ventricle per heartbeat) and the number of beats per minute. Cardiac output is commonly measured by the thermodilution technique.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Mean Blood Pressure (MBP) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour
The MBP was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. MBP was calculated as sum of diastolic blood pressure (DBP) and (0.33\*\[SBP-DBP\])
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour
Change From Baseline in Cardiac Index (CI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The CI was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. CI was calculated by dividing CO and body surface area.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Stroke Volume (SV) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The SV was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. Stroke volume is the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. SV was calculated by dividing CO and heart rate (HR).
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Stroke Volume Index (SVI) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The SVI was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. Stroke volume is the volume of blood ejected from a ventricle at each beat of the heart, equal to the difference between the end-diastolic volume and the end-systolic volume. The stroke volume index is a method of relating the stroke volume to the size of the person by dividing the stroke volume by the body surface area (BSA).
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Change From Baseline in Systemic Vascular Resistance (SVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour
The SVR was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. SVR was calculated by dividing (80\*\[MBP-MRAP\]) and CO.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
The PVR (force that opposes the flow of blood through a vascular bed) was a calculated hemodynamic parameter and the calculation was done on the basis of the measured hemodynamic parameters. PVR was calculated by dividing (80\*\[MPAP-PCWP\]) and CO.
Time frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score
Assessment of Dyspnea (difficult or labored breathing) was done using Borg scale. It is a 10-point scale where following scores stands for severity of dyspnea: 0=no breathlessness at all; 0.5=very very slight (just noticeable); 1=very slight; 2=slight; 3=moderate; 4=somewhat severe; 5=severe; 7=very severe breathlessness; 9=very very severe (almost maximum) and 10=maximum.
Time frame: Baseline, 1 h and 24 h
Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score
Assessment of Dyspnea was done using Likert scale. It is a 7-point scale where following scores stands for severity of dyspnea: 1=markedly better; 2=moderately better; 3=minimally better; 4=no change; 5=minimally worse; 6=moderately worse and 7= markedly worse
Time frame: 3, 6 and 24 hour
Number of Participants With Orthopnea
Assessment of dyspnea was done by measuring percentage of participants showing presence or absence of orthopnea (it is the sensation of breathlessness in the recumbent position, relieved by sitting or standing) symptoms
Time frame: Baseline, 1 and 24 hour
Number of Participants With Oxygen Therapy
Assessment of dyspnea was done by measuring number of participants showing presence or absence of oxygen therapy.
Time frame: Baseline,1 and 24 hour
Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2)
Assessment of dyspnea was done by measuring SpO2 via pulse oximetry, by making the participant lye quietly in the post anesthesia care unit (PACU) and breathing room air (RA)
Time frame: Baseline, 1, 2, 3, 6, 9, 12, 15 and 24 hour
Assessment of Dyspnea Using Respiratory Rate
Assessment of dyspnea was done by measuring respiratory rate which is the number of times an organism breathes with the lungs (respiration) per unit time, usually per minute
Time frame: Baseline, 1, 2, 3, 6, 9, 15 and 24 hour
Urinary Volume
The urinary volume was measured because nesiritide has a diuretic effect. Measurement of hour urine was done in the observation period and treatment period. 1-hour urine before treatment initiation was measured in the observation period. In the treatment period, 1-hour urine for period 1 and 3-hour urine for period 2 was measured. Urinary volume was recorded for participants without urethral catheterization having spontaneous micturition when needed.
Time frame: Baseline, 3 and 24 hour