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Trial registered on ANZCTR


Registration number
ACTRN12613001060730
Ethics application status
Approved
Date submitted
20/09/2013
Date registered
23/09/2013
Date last updated
30/07/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2 Multi-Centre Study to Characterise the Pharmacodynamics of Vessel Dilator Peptide (VSDL) in Patients with Acute Decompensated Congestive Heart Failure to be assessed by effects on renal function.
Scientific title
A Phase 2 Multi-Centre Study to Characterise the Pharmacodynamics of Vessel Dilator Peptide (VSDL) in Patients with Acute Decompensated Congestive Heart Failure to be assessed by effects on renal function.
Secondary ID [1] 283269 0
Nil Known
Universal Trial Number (UTN)
U1111-1148-2586
Trial acronym
CONTINUUM-HF
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Decompensated Congestive Heart Failure 290142 0
Condition category
Condition code
Cardiovascular 290531 290531 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study medication is Human pro-ANP (31-67).
Participants will be randomised into one of three groups.
For the 1 hour intravenous infusion the two drug groups will receive the same dose of drug 100ng/kg/min.
The subcutaneous infusion dosing of 12 hours on and 12 hours off is for a minimum of three days and a maximum of six days.
Group A-Placebo as described below in the Comparator / control treatment field
Group B- Low dose will receive 450 ug/hr for the first 5 hours and then 135 ug/hr for the next 7 hours.
Group C-High dose will receive 1800 ug/hr for the first 5 hours and then 540 ug/hr for the next 7 hours.
Close monitoring will occur using adverse event monitoring, vital signs including ECG monitoring,vital signs, urine volume and fluid input monitoring, physical examinations and laboratory assessments.
As all study drug is administered in hospital this allows for greater compliance and closer monitoring.
Follow up is at 30 days by a clinic visit and a 6 month follow up phone call.
Intervention code [1] 287995 0
Treatment: Drugs
Comparator / control treatment
For the placebo arm 0.9% sodium chloride is used for the intravenous 1 hour infusion given at the same rate as the study medication.
For the subcutaneous infusion Elliott's B solution is used as the placebo at the same rates as for Groups B and C above.
Follow up is a clinic visit at 30 days and a phone or email contact at 6 months.
Control group
Placebo

Outcomes
Primary outcome [1] 290559 0
The change in creatinine clearance from baseline up to 72 hours from the single 1 hour intravenous VSDL infusion assessed by measuring the serum creatinine in the blood and then using the Cockcroft-Gault formula to formulate the GFR at baseline and then at 72 hours
Timepoint [1] 290559 0
72 hours post the intravenous dose.
Secondary outcome [1] 304790 0
Total urinary output at 24 hours post IV dose as assessed by measuring all urine output from the start of the IV infusion to 24 hours post the commencement of the infusion.
Timepoint [1] 304790 0
24 hours post intravenous dose of study drug
Secondary outcome [2] 304791 0
Change in renal function (creatinine clearance) assessed by measuring the serum creatinine in the blood and then using the Cockcroft-Gault formula to formulate the GFR at baseline and then at 30 days.
Timepoint [2] 304791 0
30 days post randomisation
Secondary outcome [3] 304793 0
Change in NT-proBNP from baseline using the measurement of NT-ProBNP in the blood at 2 timepoints.
Timepoint [3] 304793 0
72 hours and 30 days from randomisation
Secondary outcome [4] 304794 0
CV death/rehospitalisation, this will be assessed by questioning the patient at a follow up visit, by medical or clinic notes or from other documentation ie family notify of patient's
death and then a death certificate is obtained with the cause of death.
Timepoint [4] 304794 0
30 days and 6 months post randomisation
Secondary outcome [5] 304795 0
Changes in 7-point Likert Dyspnoea scale as assessed by the completion of the Likert scale document by the participant at the various time points.
Timepoint [5] 304795 0
Immediately before the intravenous dose, 24 hours, 72 hours, discharge, and 30-days post randomisation
Secondary outcome [6] 304797 0
Changes in Minnesota Heart Failure Questionnaire as assessed by the completion of the Minnesota Heart Failure Questionnaire document by the participant at the various time points.
Timepoint [6] 304797 0
Immediately before the intravenous dose, and 30-days post randomisation.

Eligibility
Key inclusion criteria
Patients who are hospitalised with acute decompensated congestive heart failure and
LVEF = 45% and
GFR 25-90 mls/min as assessed by Cockcroft and Gault and
NTproBNP > 1000pg/mL and
Must be able to be hospitalised for a further 72 hours post-IV infusion.
Non-pregnant females
Signed Informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Acute ST elevation myocardial infarction (STEMI)
Pulmonary embolism (PE)
Severe valvular heart disease
B/P < 90mm Hg.
Congenital heart defects
Cardiac surgery within 4 weeks
Cerebrovascular accident within 4 weeks
Presence of hepatic impairment

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)
A subject will be enrolled if they meet all inclusion criteria and no exclusion criteria and have signed an informed consent after being given adequate time to read and consider the study and ask questions.
The subject will then be enrolled and the investigator will be unaware of the treatment allocation the subject receives as the central randomisation will be completed online and only a treatment number will be given.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation will be used.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size estimation is based on the primary efficacy endpoint, nominal change from baseline in creatinine clearance at 72 hours after IV dose infusion start in the VSDL treatment arms. Assuming a standard deviation around the change in creatinine clearance of 16 mL/min, 26 patients in each VSDL treatment arm will provide 90% power to detect change in creatinine clearance of 16 mL/min or greater with a 2-sided alpha of 0.05. An additional 13 patients will be randomized into a placebo arm, for a total of 65 patients enrolled in the study. Although this study is not adequately powered to compare the active treatment groups to placebo, these relationships will be explored as a secondary objective.
Due to the exploratory nature of the study, standard summary statistics will be used and all statistical methods will be descriptive.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
1/04/2014
Actual
7/08/2014
Date of last participant enrolment
Anticipated
Actual
7/08/2014
Date of last data collection
Anticipated
Actual
11/02/2015
Sample size
Target
65
Accrual to date
Final
1
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA

Funding & Sponsors
Funding source category [1] 288010 0
Commercial sector/Industry
Name [1] 288010 0
Madeleine Pharmaceuticals Pty Ltd
Country [1] 288010 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
South Australian Health and Medical Research Institute
Address
North Terrace,
Adelaide SA 5000
Country
Australia
Secondary sponsor category [1] 286731 0
None
Name [1] 286731 0
Address [1] 286731 0
Country [1] 286731 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289934 0
Royal Adelaide Hospital Research Ethics Committee
Ethics committee address [1] 289934 0
Royal Adelaide Hospital, North Terrace SA 5000
Ethics committee country [1] 289934 0
Australia
Date submitted for ethics approval [1] 289934 0
28/08/2013
Approval date [1] 289934 0
12/02/2014
Ethics approval number [1] 289934 0
HREC/13/RAH/342

Summary
Brief summary
The CONTINUUM-HF study aims to evaluate whether vessel dilator peptide VSDL has effects on renal function in participants with acute decompensated congestive heart failure. It shall also evaluate the tolerability and safety of VSDL over 7 day dosing, and assess the pharmacodynamics of VSDL in these participants.
The study is a multi-centre, blinded, randomised, placebo-controlled, multi-dose study to be conducted in 8 sites in Australia targeting two target peak concentrations following 1-hour intravenous bolus and daily 12-hour subcutaneous infusions for up to 7 days. The target plasma VSDL concentrations of 5ng/ml and 20ng/ml are chosen to reflect well tolerated and efficacious concentrations in previous trials using this drug.
Study subjects shall be reviewed post-IV infusion, at 72 hours, pre-discharge, and at 30 days. A 6 month followup contact will be made via phone call or email.
Participants will be given a diary to record any adverse events, changes in medication and visits to doctors.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43146 0
Prof Stephen Nicholls
Address 43146 0
South Australia Health and Medical Research Institute, North Terrace, Adelaide. SA 5000
Country 43146 0
Australia
Phone 43146 0
+61 8 8128 4510
Fax 43146 0
Email 43146 0
[email protected]
Contact person for public queries
Name 43147 0
Christine Edwards
Address 43147 0
South Australia Health and Medical Research Institute, North Terrace, Adelaide. SA 5000
Country 43147 0
Australia
Phone 43147 0
+61 8 8128 4511
Fax 43147 0
+61 8 8128 4004
Email 43147 0
[email protected]
Contact person for scientific queries
Name 43148 0
Stephen Nicholls
Address 43148 0
South Australia Health and Medical Research Institute, North Terrace, Adelaide. SA 5000
Country 43148 0
Australia
Phone 43148 0
+61 8 8128 4510
Fax 43148 0
Email 43148 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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