None listed
Conditions
Brief summary
About 1,000 people per year are admitted to Christchurch hospital with Acute Decompensated Heart Failure (ADHF) which is the inability of the heart to pump efficiently, resulting in symptoms like shortness of breath at rest or with minimal activity. The average length of hospital stay for these people is 6 days. Urocortin 2 is a naturally occurring hormone which we have shown to have promising beneficial effects in stable human heart failure. We therefore propose a randomised controlled trial to assess the impact of urocortin 2 on heart hormone activity and kidney function in addition to fluid volume status and shortness of breath symptoms in patients requiring admission to hospital for treatment of ADHF. Once consent is obtained, participants will be given (in addition to the standard treatment) urocortin 2 or placebo as a continuous intravenous infusion (IV) of urocortin 2 or placebo for up to 4 hours. A total of 50 people will be recruited, 25 to each treatment group. Serial assessment of symptoms, physical signs, blood pressure, heart rate, observed jugular venous pressure, renal function (plasma and urine creatinine and urine volume, creatinine, sodium and potassium excretion) and serial plasma neurohormone levels will be carried out over 24 hours in all 50 patients, Within each group, a sub-group of 10 people will undergo right heart catheter studies in addition to a serial blood tests undertaken in all 50 participants. Follow-up observations will include blood pressure, heart rate, renal function and symptom status pre-discharge and clinical events out to 30 days post-discharge
Interventions
We will compare the effects of standardised conventional treatment (CT) with diuretics and vasodilators in 25 patients to CT plus a once only intravenous infusion (IV) of urocortin 2 (UCN2 at 5ng/kg/min for 4 hours; n=25) in patients recruited within 24 hours of admission with Acute Decompensated Heart Failure (ADHF). Serial assessment of symptoms, physical signs, arterial blood pressure, heart rate, observed jugular venous pressure , plasma and urine creatinine and urine volume, creatinine, sod
We will compare the effects of standardised conventional treatment (CT) with diuretics and vasodilators in 25 patients to CT plus a once only intravenous infusion (IV) of urocortin 2 (UCN2 at 5ng/kg/min for 4 hours; n=25) in patients recruited within 24 hours of admission with Acute Decompensated Heart Failure (ADHF). Serial assessment of symptoms, physical signs, arterial blood pressure, heart rate, observed jugular venous pressure , plasma and urine creatinine and urine volume, creatinine, sodium and potassium excretion and serial plasma neurohormone levels (urocortins 1 and 2, cardiac natriuretic peptides, renin, angiotensin, aldosterone, catecholamines, endothelin, adrenomedullin , cortisol, urotensin2, Cyclic adenosine monophosphate (cAMP) and Cyclic guanosine monophosphate (cGMP) will be carried out over 24 hours in all 50 patients, with the addition of right heart catheter monitoring of central cardiac haemodynamic status in subgroups of 10 patients in each treatment limb. Follow-up observations will include blood pressure, heart rate, renal function and symptom status pre-discharge and clinical events out to 30 days post-discharge.
Sponsors
Health Research Council of New Zealand
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Men or women, 18 years of age or older. Admitted with Acute Decompensated Heart Failure (ADHF) suffering dyspnoea at rest or with minimal activity (i.e.breathless while sitting or lying flat or with one pillow or with minimal activity such as talking and eating). At least one of the following: -respiratory rate >20 breaths per minute, or -pulmonary oedema with crackles to at least one-third above lung bases At least one of the following: -chest x-ray showing pulmonary congestion/oedema - brain natriuretic peptide (BNP) >115pmol/L (i.e. >400pg/ml) or N-terminal Pro Brain Natriuretic Peptide (NT-proBNP) >120pmol/L (i.e. >1,000pg/ml) -pulmonary capillary wedge pressure (PCWP) >20mmHg -left ventricular ejection fraction (LVEF) <40% on echocardiography Signed informed consent
Exclusion criteria
Admitted for > 36 hours before commencement of trial therapy. Baseline systolic blood pressure of <100mmHg. Acute coronary syndrome. Significant cardiac valve stenosis, restrictive cardiomyopathy, hypertrophic cardiomyopathy or pericardial tamponade. First intravenous doses of diuretics, vasodilators or inotropes more than 24 hours before randomisation. Intravenous nitrate or inotrope (dobutamine) with dosage not stable for 3 hours before randomisation. Co-morbidity - End stage renal disease. - Significant chronic lung disease interfering with assessment of dyspnoea. - Non-cardiac disease with a life expectancy <6 months Participation in research involving another experimental drug or device within last 30 days. Women with child bearing potential. Body Mass Index (BMI) exceeding 32 Incapable of informed consent or compliance with study protocol requirements.
Outcome results
None listed