Acute decompensated heart failure (adHF) MedDRA version: 7.1 Level: LLT Classification code 10000803
Conditions
Interventions
Trade Name: Natrecor
Product Name: nesiritide
Product Code: GW832810
Pharmaceutical Form: Powder for solution for infusion
INN or Propos
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be considered eligible for inclusion in this study only if all of the following criteria apply: 1. Male or female, at least 18 years of age and who has been hospitalised for the management of a primary diagnosis of adHF. Note for the small number of female subjects of childbearing potential who may enter the study an effective method of contraception must be used for the duration of the study (up to Day 30) 2. The underlying primary aetiology of adHF and the presenting symptoms should be cardiac disease, rather than pulmonary disease (e.g. not cor pulmonale, nor pneumonia in addition to chronic HF) 3. In relation to the acute episode, subjects must have at least one sign of heart failure as detailed below: • tachypnoea (> 20 breaths/minute) • increased jugular venous pressure (JVP), or 3rd/4th heart sound, or recent clinically significant weight gain indicative of oedema, or hepatic congestion. • crackles/rales or pulmonary effusion evident on chest auscultation/ examination. 4. In relation to the acute episode, subjects must have at least one piece of investigational evidence consistent with heart failure as detailed below: • a chest X-ray upon admission with evidence of pulmonary congestion • Left ventricular systolic ejection fraction performed within the past 12 months - Left ventricular ejection fraction should be =45% or the equivalent rating of at least moderately impaired left ventricular systolic function. 5. Subjects must still have dyspnoea at rest or on minimal exertion (e.g. on sitting up) at the time of randomisation 6. Subjects must have received at least one but not more than two doses of IV bolus diuretic within 24 hours prior to randomisation AND/OR, have been receiving a continuous infusion of IV diuretics for at least 2 hours immediately prior to randomisation at a constant dose. Bolus IV diuretic is not permitted within 1 hour prior to randomisation. The subject must be randomised within 24 hours of the initiation of IV treatment for HF. 7. Chronicity of HF must be substantiated by: 1) documented clinical history of chronic HF and 2) investigational evidence of left ventricular systolic dysfunction (e.g. by echocardiography, ventriculography or nuclear cardiography) within the last 12 months. A current assessment (e.g. echocardiographic) can be performed if this information is not available from the medical history at the time of screening. NB: Left ventricular ejection fraction should be =45% or the equivalent rating of at least moderately impaired left ventricular systolic function 8. The subject or legal representative must fully understand and sign the written informed consent prior to initiation of protocol-specified procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Initiation of IV treatment for HF > 24 hours prior to randomisation 2. Hospitalised for =48 hours prior to randomisation 3. Baseline SBP a. Subjects who have not received or are not receiving either IV vasodilators (e.g. nitrates) or inotropes prior to randomisation are excluded if SBP = 100mmHg. b. Subjects who have received or are receiving either IV vasodilators (e.g. nitrates) or inotropes prior to randomisation are excluded if SBP 190/115 mmHg). 8. History of unexplained syncope 9. Requiring mechanical ventilation, or mechanical circulatory support (e.g. intraaortic balloon pump, left ventricular assist devices) (subjects receiving CPAP prior to randomisation may be recruited), or likely to require dialysis or other renal replacement therapy post randomisation, or likely to undergo percutaneaous coronary intervention (PCI) or emergency surgery during admission. 10. Subjects who have been resuscitated or received defibrillation during the admission prior to randomisation. 11. Known allergic reaction to nesiritide or other IV therapy that may be critical to successful management of adHF (e.g. nitrate, inotropes, diuretics) 12. The following co-morbidities: cardiac valvular stenosis, restrictive cardiomyopathy, hypertrophic obstructive cardiomyopathy, pericardial tamponade or any condition likely to cause intolerance to vasodilators, severe pulmonary disease, concurrent pneumonia, 13. adHF associated with: underlying congenital heart disease, thyrotoxicosis (or other conditions associated with high output cardiac failure), active myocarditis; or with uncontrolled haemodynamically relevant atrial fibrillation/flutter; or with ventricular rhythm disturbances or secondary to clinical evidence of digoxin toxicity or any other drug-related toxicity. 14. Subjects with other significant, non-cardiac, co-morbidities (e.g. cancer) who are not anticipated to survive the 6 month follow-up 15. Subjects whose condition requires long term IV vasoactive support (e.g. heart transplant candidate) or subjects whose acute cardiovascular condition is unlikely to be sufficiently improved to enable the subject to be discharged following study therapy 16. Subjects who have undergone a heart transplant or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of this study are to assess the efficacy and safety of IV nesiritide versus placebo, in addition to background care, in the treatment of subjects with adHF managed in an inpatient setting reflecting mainstream clinical practice. Primary Objective • To evaluate the efficacy of nesiritide versus placebo, in addition to background care by assessing dyspnoea and well-being at 3 hours and 6 hours after the start of investigational product. The study will be considered a success if improvement in subject self-assessed dyspnoea (at either 3 or 6 hours, or both) and in subject self-assessed well-being (at either 3 or 6 hours, or both) is shown. ; Secondary Objective: • To assess the effect of nesiritide versus placebo, in addition to background care, on other efficacy parameters including mortality and readmissions, clinical status and endpoints relating to length of hospital stay and degree of care required • To assess the safety of nesiritide versus placebo, in addition to background care, in subjects with adHF ; Primary end point(s): Co-Primary Endpoints: • Subject self-assessed dyspnoea at 3 hours • Subject self-assessed dyspnoea at 6 hours • Subject self-assessed well being at 3 hours • Subject self-assessed well being at 6 hours | — |
Countries
Belgium, Czech Republic, Denmark, Estonia, Finland, Hungary, Iceland, Ireland, Latvia, Lithuania, Slovakia, Sweden, United Kingdom
Outcome results
None listed