An Open-label, One-arm, Study to Evaluate the Hemodynamic Changes and Safety of Nesiritide for Acute Decompensated Heart Failure

Phase 3

Completed

• Conditions: Heart Decompensation; Congestive Heart Failure
• Interventions: Drug: Nesiritide

• Registration Number: NCT00813202
• Lead Sponsor: Xian-Janssen Pharmaceutical Ltd.

Brief Summary

The present study was an open-label, uncontrolled, and multi-centered phase III clinical trial for evaluation of the efficacy (clinical efficacy and hemodynamics) and safety of nesiritide.

Detailed Description

This was an open-label, uncontrolled, and multi-centered phase II clinical trial for evaluation of the clinical efficacy and hemodynamics and safety of nesiritide. The study was conducted in hospital setting and all patients exhibited symptoms of acute decompensated heart failure, requiring treatment with intravenous drug administration. The total duration was 180 days, including a screening phase, an open treatment phase (24 hours in all) and a safety follow-up phase (day 30 and day 180). Screening phase: Right heart floating catheter was placed for patients with acute decompensate heart failure who met the inclusion criteria while not the exclusion criteria to measure pulmonary capillary wedge pressure. The results should be =20 mmHg. Open treatment phase: Nesiritide was administered by intravenous injection at a dose of 2 µg/kg for 60 second, followed by intravenous infusion at a dose of 0.01 µg/kg for 24 hour. All the patients were monitored for hemodynamics for 24 hour. Safety follow-up phase: On day 30, all the patients were required to return to the study center for follow-up. Information about death, severe adverse event, re-hospitalization and serum creatinine was collected. On day 180, all the patients were followed up by telephone. Information about death and severe adverse event was collected. Pulmonary capillary wedge pressure will be measured at 15 minutes, 1 hour, 3 hour and 24 hour, compared with baseline value. Nesiritide is white to off-white sterile lyophilized lump or powder, supplied in transparent 5 mL glass vials. The investigational drug was administered via infusion pump. Infusion rate was adjusted according to body weight. The drug was administered directly via venous cannula or the nearest injection port to the venous cannula for 60 second. The dosage of nesiritide was 2 µg/kg. The infusion rate of nesiritide was adjusted to 0.01 µg/kg/min (cannot exceed 0.01 µg/kg/min).

Study Timeline

• Study Start: 2006-10
• Primary Completion: 2007-06
• Study Completion: 2007-06
• Study First Submitted: 2008-12-18
• Study First Submitted QC: 2008-12-18
• Study First Posted: 2008-12-22
• Status Verified: 2014-02
• Last Update Submitted: 2014-02-26
• Last Update Posted: 2014-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

Inclusion Criteria

• Systolic blood pressure> 90 mmHg
• The subjects must present with dyspnoea at resting state or with minimum activity amount (such as standing up)
• Onset at this time was complicated with symptoms of acute decompensate heart failure, and it was serious enough to call for hospitalization and treatment with intravenous drug administration
• Acute decompensate heart failure was caused by cardiogenic factors rather than pulmonary factors (for example, it was neither cor pulmonale nor chronic heart failure complicated with pneumonia)
• The patients must have at least two of manifestations that related with this acute onset.

Exclusion Criteria

• Patients with systolic blood pressure =90 mmHg
• patients who had been administered with intravenous nitroglycerin or other intravenous vasoactive drugs within 2 hour before administration of the investigational drug
• Patients who had known or suspected acute coronary syndrome (Myocardial infarction with or without increased ST segment, or unstable myocardial infarction) within 2 weeks before administration of the investigational drug
• Patients with cardiac shock or clinical manifestation of uncorrected hypovolemia or sodium depletion (such as clinical signs of excessive diuresis or dehydration), or clinical manifestation induced by other forbidden venous vasoactive agents
• Patients with such extremely emergent and unstable clinical conditions that not tolerant to Swan-Ganz catheter or temporal baseline evaluation
• patients with obvious cardiac valvular stenosis (subjects treated by valve-replacement can be included), hypertrophic, restrictive, or obstructive myocardial disease, primary pulmonary hypertension, or complex congenital heart disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nesiritide	Nesiritide	-

Primary Outcome Measures

Name	Time	Method
Change in pulmonary capillary wedge pressure	Baseline, 180 days	Pulmonary capillary wedge pressure will be measured in patients at all time points after administration of nesiritide, and the difference will be compared with baseline value (P\<0.001).

Secondary Outcome Measures

Name	Time	Method
Change in clinical symptoms and overall clinical efficacy	Baseline, 180 days	Nesiritide will attenuate dyspnoea. Nesiritide will also improve clinical symptoms and Nesiritide will improve overall clinical efficacy.