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Trial registered on ANZCTR


Registration number
ACTRN12609000508279
Ethics application status
Approved
Date submitted
22/06/2009
Date registered
25/06/2009
Date last updated
2/12/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised, double-blind, placebo-controlled parallel group, single centre study evaluating neurohumoral, haemodynamic and renal effects of UrocortiN 2 administered In addition to COnventional care compared with placebo administered in addition to standaRd care in subjects with Acute DecompeNsated Heart Failure
Scientific title
A randomised, double-blind, placebo-controlled parallel group, single centre study evaluating neurohumoral, haemodynamic and renal effects of UrocortiN 2 administered In addition to COnventional care compared with placebo administered in addition to standaRd care in subjects with Acute DecompeNsated Heart Failure
Secondary ID [1] 283667 0
nil known
Universal Trial Number (UTN)
Trial acronym
UNICORN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Decompensated Heart Failure 237072 0
Condition category
Condition code
Cardiovascular 237393 237393 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 236791 0
Treatment: Drugs
Comparator / control treatment
The matching placebo consists of 50 mg per vial of mannitol as a sterile, lyophilized white powder in 5 mL vials for reconstitution in an intravenous infusion (IV) in 50 mL normal saline.
Control group
Placebo

Outcomes
Primary outcome [1] 238193 0
Change in neurohormonal status will be assessed by measuring 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) in all 50 patients over 24 hours.
Timepoint [1] 238193 0
within the first 24 hours of administration of intravenous urocortin 2 or placebo
Secondary outcome [1] 242499 0
Change in Renal function will be measured by serial assessment of plasma and urine creatinine and urine volume, creatinine, sodium and potassium excretion.
Timepoint [1] 242499 0
within the first 24 hours of administration of intravenous urocortin 2 or placebo

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Subjects will be randomised to receive standardised conventional treatment (CT) or standardised conventional treatment with the addition of a 4 hour infusion of urocortin 2 (UCN2 group) at a dose of 5ng/kg/minute (equating to approximately 25µg/hour for an 80kg patient). A total of 50 patients will be recruited with 25 within each treatment limb. Within each treatment limb a sub-group of 10 patients will undergo right heart catheter studies in addition to a common panel of neurohumoral, renal, haemodynamic and symptom measures undertaken in all 50 participants
In 10 patients within each study treatment limb, a right heart catheter will be deployed using ultrasound location of the internal jugular vein as the access point. A Swan-Ganz catheter will be used to measure right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac output (thermodilution) at -30 minutes, time zero, +30 minutes and +1, 2, 3, 4, 5, 6, 7 and 8 hours relative to commencement of randomised treatment. Swan-Ganz catheters will be removed after 8 hours.
The 10 patients in each limb will constitute 40% of each group. They will be selected randomly by random number generation as provided by our biostatistician. They will provide direct measurements of cardiac hemodynamics over a more sustained period than they can be derived from intermittent echo with associated indirect measurement. This element will introduce no bias. Allocation concealment will be managed by central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Subjects will be randomised to receive standardised conventional treatment (CT) or standardised conventional treatment with the addition of a 4 hour infusion of urocortin 2 (UCN2 group) at a dose of 5ng/kg/minute (equating to approximately 25µg/hour for an 80kg patient). A total of 50 patients will be recruited with 25 within each treatment limb. Within each treatment limb a sub-group of 10 patients will undergo right heart catheter studies in addition to a common panel of neurohumoral, renal, haemodynamic and symptom measures undertaken in all 50 participants
In 10 patients within each study treatment limb, a right heart catheter will be deployed using ultrasound location of the internal jugular vein as the access point. A Swan-Ganz catheter will be used to measure right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure and cardiac output (thermodilution) at -30 minutes, time zero, +30 minutes and +1, 2, 3, 4, 5, 6, 7 and 8 hours relative to commencement of randomised treatment. Swan-Ganz catheters will be removed after 8 hours.
The 10 patients in each limb will constitute 40% of each group. They will be selected randomly by random number generation as provided by our biostatistician. They will provide direct measurements of cardiac hemodynamics over a more sustained period than they can be derived from intermittent echo with associated indirect measurement. This element will introduce no bias
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 1848 0
New Zealand
State/province [1] 1848 0

Funding & Sponsors
Funding source category [1] 237189 0
Government body
Name [1] 237189 0
Health Research Council of New Zealand
Address [1] 237189 0
PO Box 5541 Wellesley Street, Auckland, New Zealand 1141
Country [1] 237189 0
New Zealand
Primary sponsor type
Government body
Name
Health Research Council of New Zealand
Address
PO Box 5541 Wellesley Street, Auckland, New Zealand 1141
Country
New Zealand
Secondary sponsor category [1] 4682 0
None
Name [1] 4682 0
Address [1] 4682 0
Country [1] 4682 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 239282 0
Upper South B Regional Ethics Committee
Ethics committee address [1] 239282 0
PO Box 3877 Christchurch 8140
Ethics committee country [1] 239282 0
New Zealand
Date submitted for ethics approval [1] 239282 0
Approval date [1] 239282 0
15/06/2009
Ethics approval number [1] 239282 0
URB/08/03/009

Summary
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
Trial website
Trial related presentations / publications
Findings From the UNICORN Study (Urocortin-2 in the Treatment of Acute Heart Failure as an Adjunct Over Conventional Therapy) W. Y. Wandy Chan, MBChB; Christopher M. Frampton, PhD; Ian G. Crozier, MD†; Richard W. Troughton, MD, PhD, A. Mark Richards, MD, PhD
JCHF. 2013;1(5):433-441. doi:10.1016/j.jchf.2013.07.003 .
Public notes

Contacts
Principal investigator
Name 29779 0
Prof Mark Richards
Address 29779 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
New Zealand
Country 29779 0
New Zealand
Phone 29779 0
+643 364 0640
Fax 29779 0
+643 364 1115
Email 29779 0
mark.richards@cdhb.health.nz
Contact person for public queries
Name 13026 0
Ms Lorraine Skelton
Address 13026 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 13026 0
New Zealand
Phone 13026 0
+643 364 1063
Fax 13026 0
+643 364 1115
Email 13026 0
lorraine.skelton@cdhb.govt.nz
Contact person for scientific queries
Name 3954 0
Prof Professor Mark Richards
Address 3954 0
Department of Medicine
University of Otago, Christchurch
PO Box 4345
Christchurch 8140
Country 3954 0
New Zealand
Phone 3954 0
+643 364 1117
Fax 3954 0
+643 364 1115
Email 3954 0
mark.richards@cdhb.govt.nz

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary