Clinical trial NCT00490724: An Exploratory Study of Nesiritide in Participants With Acute Heart Failure
Official title: An Exploratory Study of JNS004 (Nesiritide) in Patients With Acute Heart Failure (J2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Heart Failure, Congestive
Keywords: Heart failure, congestive
Nesiritide and
JNS004
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2007-06-25
Enrollment: 67
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Participants with acute heart failure (including acute exacerbation of chronic heart failure) requiring hospitalization whose placement of right-heart catheter (flexible, tube-like tool used to take fluids out or put fluids into the body) is judged to be possible and useful for treatment
* Participants with findings of pulmonary (having to do with the lungs) congestion on a chest X-ray (an image of a site produced on photographic film by X-rays passing through the site) film taken within 12 hours before starting the treatment
* Participants with 2 systolic blood pressure (SBP: refers to blood pressure \[pressure of the blood on the arteries and other blood vessel\] when the heart beats while pumping blood) values greater than or equal to 100 millimeters of mercury (mmHg) measured at an interval of at least 15 minutes in the hemodynamic (related to blood flow) assessment in observation period
* In a hemodynamic assessment in observation period, participants with 2 pulmonary capillary wedge pressure (PCWP \[if it is not available, pulmonary arterial diastolic pressure {PADP}\]) values greater than or equal to 18 mmHg measured at an interval of at least 15 minutes and the second measurement value is within positive 20 percent (%) and negative 20% compared with the first 1

Exclusion Criteria:

* Participants with severe (very serious, life threatening) hepatic (to do with liver) impairment or renal (to do with kidney) impairment, cancer (abnormal tissue that grows and spreads in the body until it kills), or malignant (cancerous) tumor (a mass in a specific area)
* Participants who are or may be pregnant or breast-feeding
* Participants receiving non-invasive (puncture, opening or cutting of the skin) positive pressure ventilation (NIPPV) or scheduled to receive this during the study period
* Participants who received treatment with another investigational product within 4 weeks before the initiation of investigational treatment or who were enrolled in a clinical study of nesiritide in the past
* Participants who received prohibited concomitant medications within 3 hours before the initiation of investigational treatment or those who are receiving such a medication

Primary outcomes:
measure: Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP or Pulmonary Arterial Diastolic Pressure[PADP]) at 3 Hours
timeFrame: Baseline and 3 Hours
Secondary outcomes:
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12 and 24 Hour
measure: 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
timeFrame: Baseline, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, 15 and 24 Hour
measure: Number of Participants With Dyspnea Symptoms Assessed by Borg Scale Score
timeFrame: Baseline, 1 h and 24 h
measure: Number of Participants With Dyspnea Symptoms Assessed by Likert Scale Score
timeFrame: 3, 6 and 24 hour
measure: Number of Participants With Orthopnea
timeFrame: Baseline, 1 and 24 hour
measure: Number of Participants With Oxygen Therapy
timeFrame: Baseline,1 and 24 hour
measure: Assessment of Dyspnea Using Percutaneous Arterial Oxygen Saturation (SpO2)
timeFrame: Baseline, 1, 2, 3, 6, 9, 12, 15 and 24 hour
measure: Assessment of Dyspnea Using Respiratory Rate
timeFrame: Baseline, 1, 2, 3, 6, 9, 15 and 24 hour
measure: Urinary Volume
timeFrame: Baseline, 3 and 24 hour
Other outcomes:
Locations:
city: Amagasaki
country: Japan
city: Chikushino
country: Japan
city: Hiroshima
country: Japan
city: Ikoma
country: Japan
city: Komatsushima
country: Japan
city: Kumamoto
country: Japan
city: Moriyama
country: Japan
city: Osaka
country: Japan
city: Saitama
country: Japan
city: Tokyo
country: Japan
city: Yokohama
country: Japan
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: