Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000998246
Ethics application status
Approved
Date submitted
13/11/2009
Date registered
18/11/2009
Date last updated
15/07/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Reducing symptoms in acute Acute Heart Failure with a man made vessel dilator peptide
Scientific title
An Exploratory, Single Centre, Open Label, single and Multidose, Safety and Efficacy Study of the Treatment of Acute Decompensated Congestive Heart Failure with Vessel Dilator Peptide by Intravenous Infusion.
Secondary ID [1] 1130 0
MP3167-1
The Sponsor_Madeleine Pharmaceuticals
Secondary ID [2] 1131 0
Made001 ADCHF

theThe Sponsor_Madeleine Pharmaceuticals in reference to the Peptide
Universal Trial Number (UTN)
U1111-1112-4985
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Decompensated Congestive Heart Failure (ADCHF) 252198 0
Condition category
Condition code
Cardiovascular 252388 252388 0 0
Other cardiovascular diseases
Respiratory 252391 252391 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Examine whether administration of Vessel Dilator (VSDL) to ADCHF patients in single and multi-dosage regimes induce changes in hemodynamic parameters with renal, natriuretic and diuretic effects as seen in the treatment of CHF patients without serious adverse side-effects (SAE);
1.Single dose of intravenous (IV) VSDL in saline at 50 ng/kg/min for 60 min (n=6)
2.Single dose of IV VSDL in saline at 100 ng/kg/min for 60 min (n=6)
3.Single dose of IV VSDL in saline at 200 ng/kg/min for 60 min (n=6)
4.Standard method of care for the treatment of ADCHF (n=6)
5.Multiple dose of IV VSDL in saline at most appropriate dose (50, 100 or 200 ng/kg/min) for 60 min at 0 h, 12 h, and 24 h (n=6)
6.Multiple dose of IV VSDL in saline at most appropriate dose (50, 100 or 200 ng/kg/min) for 60 min at 0 h, 6 h and 12 h (n=6)
Intervention code [1] 241549 0
Treatment: Drugs
Comparator / control treatment
Standard Treatment is current guideline treatment for patients with ADCHF and would include the administration of intravenous diuretics, morphine and nitrates. Acutely it may also include continuous positive airways pressure ventilation and occasionally the administration of oral Angiotensin converting enzyme (ACE) inhibitors.
Control group
Active

Outcomes
Primary outcome [1] 253260 0
Change in pulmonary capillary wedge pressure (PCWP)
This will be measure via a pulmonary artery cather (Swan Ganz catheter)
Timepoint [1] 253260 0
at 24 hours following administration of drug
Primary outcome [2] 253261 0
Change in cardiac index (CI)
This will be measured via a pulmonary artery cather (Swan Ganz catheter) and trans-thoracic echocardiogram (TTE)
Timepoint [2] 253261 0
at 24 hours following administration of drug
Secondary outcome [1] 262248 0
Change in blood pressure, via automated sphygnomanometer
Timepoint [1] 262248 0
at 24 hours following administration of drug
Secondary outcome [2] 262249 0
Change in systemic vacular resistance
This will be measure via a pulmonary artery cather (Swan Ganz catheter)
Timepoint [2] 262249 0
at 24 hours following drug administration
Secondary outcome [3] 262250 0
Change in pulmonary vascular resistance This will be measure via a pulmonary artery cather (Swan Ganz catheter)
Timepoint [3] 262250 0
at 24 hours post drug administration
Secondary outcome [4] 262251 0
Change in central venous pressureThis will be measure via a pulmonary artery cather (Swan Ganz catheter)
Timepoint [4] 262251 0
at 24 hours post drug administration
Secondary outcome [5] 262252 0
Change in Ejection Fraction (EF) by Cardiac Magnetic Resonance Imaging (CMR) between groups
Timepoint [5] 262252 0
at 5days (+/- 48 hours) following drug administration
Secondary outcome [6] 262253 0
Change in Ejection Fraction (EF) by Trans-Thoracic Echocardiogram (TTE) within groups
Timepoint [6] 262253 0
at 0, 72 (+/- 24 hr) and day 5 (+/- 48 hr) following administration of drugs
Secondary outcome [7] 262254 0
Change in Borg dyspnea index
Timepoint [7] 262254 0
at 24 hours following administration of drug
Secondary outcome [8] 262255 0
Change in serum creatinine
Timepoint [8] 262255 0
at 24 hours at 24 hours after administration of drug
Secondary outcome [9] 262256 0
Change in blood urea nitrogen (BUN)
Timepoint [9] 262256 0
at 24 hours after administration of drug
Secondary outcome [10] 262257 0
Readmission rates for Major Adverse Cardiac Events (All-cause Death, Myocardial Infarction (MI), Cerebral Vascular Incidence (CVA), Recurrent Congestive Heart Failure (CHF)). Assessed by patient phone contact and review of hospital data base and patients medical records
Timepoint [10] 262257 0
at days 90 and 365 after administration of drug

Eligibility
Key inclusion criteria
Upon diagnosis of ADCHF (New York Heart Association (NYHA) class III - NYHA class IV) with evidence of the following:
1. Signed written informed consent
2. Male and/or female, 18 years or older
3. Women of child bearing potential to test negative to beta-human chorionic gonadotropin (ß-hCG)
4.Systolic dysfunction within the last 12 months (EF <40%) as determined by Trans-Thoracic Echocardiogram (TTE)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Evidence in the Emergency Department (ED) for Myocardial Infarction (MI) or high risk acute coronary syndrome within past 6 weeks, as determined by creatinine kinase (CK)/creatinine kinase muscle-brain isoenzyme (CK-MB) = 3 times upper limit of normal (as defined by Institute of Medical and Veterinary Science (IMVS)) or elevation of troponin T at baseline >0.1
2. Evidence in the ED of Acute MI (ST elevation and/or elevation of Troponin T), as determined by Trans-Thoracic electrocardiogram (TTE)
3. Hypotension (Systolic Blood Pressure (SBP)<90 mmHg), cardiogenic shock, volume depletion or any other clinical condition that would contraindicate administration of an Intravenous (IV) agent with potent vasodilatory effects
4. Persistent, uncontrolled hypertension (SBP>180 mm Hg)
5. Presence any Cardiac Magnetic Resonance (CMR) contra-indication (includes Permanent Pacemaker (PPM), cerebral aneurysm clips,
6. Congenital heart defects
7. Cardiac surgery within past 4 weeks
8. Diastolic heart failure (preserved left ventricular function - determined by history or elctrocardiogram (ECG))
9.Severe valvular heart disease: Aortic stenosis (AS), Ideopathic hypertrophic subaortic stenosis (IHSS), Hypertrpohic Obstructive Cardiomyopathy (HOCM), acute Aortic Incompetence (AI) and Mitral Regurgitation (MR)
10.History of cerebrovascular accident (within past 4 weeks)
11.Acute or chronic active infection, including pneumonia and urinary tract infection
12.Significant renal impairment as determined by a creatinine clearance of <60 ml/min
13.Prior participation in any other clinical trial within past 30 days, including present day

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Adult subjects, both male and female, will be sourced from patients presenting to the Emergency Department (ED) of the Royal Adelaide Hospital (RAH) with signs and symptoms of ADCHF.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
There is no randomisation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Patients are allocated one of the 6 arms of intervention, no randomisation is involved. Please refer to desription f intervention involved above.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/02/2010
Actual
27/08/2010
Date of last participant enrolment
Anticipated
Actual
23/04/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 244015 0
Commercial sector/Industry
Name [1] 244015 0
Madeleine Pharmaceuticals
Country [1] 244015 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Madeleine Pharmaceuticals
Address
Box 1474
Mount Barker SA 5251
Country
Australia
Secondary sponsor category [1] 251392 0
None
Name [1] 251392 0
Address [1] 251392 0
Country [1] 251392 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 258122 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 258122 0
Level 3, Hanson Institute, RAH
North Terrace ADELAIDE SA
5000
Ethics committee country [1] 258122 0
Australia
Date submitted for ethics approval [1] 258122 0
18/11/2009
Approval date [1] 258122 0
27/05/2010
Ethics approval number [1] 258122 0
091224

Summary
Brief summary
The purpose of this study is to find out if a man-made heart hormone (“MAD001”) improves the treatment of people diagnosed with acute decompensated congestive heart failure (ADCHF). This substance improves several heart functions, lowers blood pressure and increases salt (sodium) and water removal from the body, when given to animals, healthy humans and persons with chronic congestive heart failure (CHF). The purpose of this study is to determine if this substance also improves heart functionality, and to a lesser extent increases sodium and/or water removal, in persons with ADCHF to improve their condition.
Trial website
Trial related presentations / publications
No trial related citations for this study, not published as yet.
Public notes

Contacts
Principal investigator
Name 30507 0
Prof Stephen Worthley
Address 30507 0
Level 6, Theatre Block Royal Adelaide Hospital North Terrace Adelaide, South Australia (SA) 5000
Country 30507 0
Australia
Phone 30507 0
+61 8 8222 5608
Fax 30507 0
Email 30507 0
[email protected]
Contact person for public queries
Name 13754 0
Mr David Yudkin
Address 13754 0
Clinical Trial Co-ordinator
Cardiovascular Clinical Trials
L6 Outpatient Department (OPD) Royal Adelaide Hospital
North Terrace ADELAIDE
South Australia (SA) 5000
Country 13754 0
Australia
Phone 13754 0
+61 8 8222 2890
Fax 13754 0
+61 8 8222 2892
Email 13754 0
[email protected]
Contact person for scientific queries
Name 4682 0
Prof Prof Stephen Worthley
Address 4682 0
Level 6, Theatre Block
Royal Adelaide Hospital
North Terrace
Adelaide,
South Australia (SA) 5000
Country 4682 0
Australia
Phone 4682 0
+61 8 8222 5608
Fax 4682 0
+ 61 8 8222 2454
Email 4682 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIAtrial Natriuretic Peptide31–67: A Novel Therapeutic Factor for Cardiovascular Diseases2021https://doi.org/10.3389/fphys.2021.691407
N.B. These documents automatically identified may not have been verified by the study sponsor.