Clinical trial NCT00490724
Conditions: Heart Failure, Congestive
Keywords: Heart failure, congestive Nesiritide and JNS004
Sponsor: Janssen Pharmaceutical K.K.
Start date: 2007-03-01; Completion date: 2008-07-01
Enrollment: 67 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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.
Interventions: intervention 1: Nesiritide (1+0.01) intervention 2: Nesiritide (2+0.005) intervention 3: Nesritide (2+0.01)
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: 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.

Protocol documents: