Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001153707
Ethics application status
Approved
Date submitted
14/07/2022
Date registered
23/08/2022
Date last updated
23/08/2022
Date data sharing statement initially provided
23/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Cell Free DNA as a marker of inotrope related myocardial necrosis in heart failure
Scientific title
cfDNA as a marker of inotrope related myocardial necrosis in heart failure
Secondary ID [1] 307568 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 327016 0
myocardial necrosis 327017 0
Inotropes 327018 0
Condition category
Condition code
Cardiovascular 324191 324191 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Heart failure patients that have been admitted to the coronary care unit for inotrope administration will have their blood sampled by medical doctors at 4 timepoints; prior to commencing inotropes, 3 hrs post inotrope commencement, 24hrs post inotrope commencement, 24hrs post cessation of inotropes. Each blood sample will take approximately 10 minutes. This is the only requirement of the patient.

Data will be collected by the researcher from electronic hospital records and include
- Demographic data
- Co-morbidities
- Diagnosis
- medications
- Standard of care blood test results (Troponin, creatinine, CRP)
- Observations (HR, Bp, etc)
- Inotrope requirements (type, dose, length of time on infusion)
- Length of hospital stay
These will be accessed from Septemeber 2022 to September 2023
Intervention code [1] 324024 0
Diagnosis / Prognosis
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 332006 0

Change in cardiac specific cfDNA between baseline and post inotrope commencement levels
Timepoint [1] 332006 0
Blood sample times
1.. Decision to start inotrope
2. 3 hours post inotrope start
3. 24 hours post inotrope commencement
4. 24hrs post inotropes ceased.
Secondary outcome [1] 411883 0
Level of cfDNA in the blood measured against type and dose of inotrope
Timepoint [1] 411883 0
-Before inotropes initiated,
-3 hours after inotropes initiated,
-24 hours after inotropes initiated
-24 hours post inotrope cessation.

Eligibility
Key inclusion criteria
- Inpatients with FSH Advanced heart failure unit
- Consented to study participation
- Over 18 years of age
-Requiring IV administration of either
Noradrenaline
Dobutamine
Milrinone
Levosimendan
Adrenaline
Isoprenaline
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
o Intubated at time of inotrope commencement
-Post heart transplantation
- <48 hrs post PCI or device placement
- < 48 hrs post sustained VT or sustained atrial arrhythmias or any arrhythmias requiring
DCCV
- Recent MI

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Participants will patients of the Advanced Heart Failure Team who have been admitted for inotrope administration to the coronary care unit at Fiona Stanley Hospital.
Sample size
30 patients for pilot study
Consent
Patients will be invited to participate by the advanced heart failure team when the
decision is made to commence inotropes using the standard PICF

Data collection and statistical analysis
o BOSSnet, iCM and CCU/ICU clinical records

The data generated from the experimental phase of the study will be analysed and processed via GraphPad Prism software.

a. Aim #1: Cell free DNA levels pre and post inotrope therapy
To investigate the changes in total cfDNA and cardiac specific cf DNA after administration of IV inotropes, as compared to pre inotrope levels, we will be using the paired T-test, as both groups are from then same population (i.e. we are measuring cfDNA levels from the same group of patients, before and after a treatment is administered). Furthermore, the t-test will be one tailed, as we ideally wish to see whether one population mean is greater or less than the other (as a lower cfDNA mean will have implications for the true efficacy of the inotrope treatment).

b. Aim #2: Patterns of cell free DNA fragment size pre and post inotrope treatment
Similar to the above, we will use a one tailed paired t-test to evaluate whether the mean cfDNA fragment size is significantly different in treated vs untreated individuals.

c. Aim #3: Comparison between different inotropic therapies and the resulting variation in cfDNA release (as a means of testing adverse myocardial effect of different inotropes)
Unlike the previous two aims, this component of the study involves multiple independent variables that are being tested against each other- as a result, we are unable to use the t-test and must use ANOVA instead, as well as a subsequent post-hoc test. The ANOVA test will evaluate whether there is indeed a significant difference between the post treatment cfDNA amount released across different inotherapies (which has implications for the long-term adverse effects of different inotropes). If there is a statistically significant difference in the group means, we will use Tukey’s test to locate specific differences between the inotrope types (assuming that there is a homogeneity of variances in the data).

Sample Size
30 Participants – Pilot study

Study Power and Significance
As this is a pilot no power analysis is required.

Selection of participants for analyses:
All consented patients who were able to provide blood samples.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/09/2022
Actual
Date of last participant enrolment
Anticipated
1/09/2023
Actual
Date of last data collection
Anticipated
1/10/2023
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 22820 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 38109 0
6150 - Murdoch

Funding & Sponsors
Funding source category [1] 311841 0
Charities/Societies/Foundations
Name [1] 311841 0
Heart and Lung Research Institute
Country [1] 311841 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Heart and Lung Research Institute WA
Address
HLRI WA
Level 2
Harry Perkins Institute of Medical Research South
5 Robin Warren Drive
MURDOCH WA 6150
Country
Australia
Secondary sponsor category [1] 313320 0
Hospital
Name [1] 313320 0
Fiona Stanley Hospital
Address [1] 313320 0
11 Robin Warren Drive
MURDOCH WA 6150
Country [1] 313320 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311283 0
South Metropolitan Health Service Human Research Ethics Committee
Ethics committee address [1] 311283 0
Education Building
Fiona Stanley Hospital
11 Robin Warren Drive
MURDOCH WA 6150
Ethics committee country [1] 311283 0
Australia
Date submitted for ethics approval [1] 311283 0
30/05/2022
Approval date [1] 311283 0
17/06/2022
Ethics approval number [1] 311283 0

Summary
Brief summary
This study is testing a new blood marker for heart cell death called cell free DNA (cfDNA). Drugs like inotropes may cause injury to the heart muscle which current blood markers are unable to detect. We will take samples of blood from heart failure patients admitted to the Coronary Care Unit (CCU) before, during and after the commencement of inotrope treatment, as prescribed by the cardiologist. We will investigate if there is any detectable damage to the heart in association with these medications by measuring the amount of cfDNA in the blood stream.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120566 0
Ms Rebbecca Hahn
Address 120566 0
HLRI WA
Level 1
Harry Perkins Institute of Medical Research
5 Robin Warren Drive
MURDOCH WA 6150
Country 120566 0
Australia
Phone 120566 0
+61 439975860
Fax 120566 0
Email 120566 0
rebecca.hahn@health.wa.gov.au
Contact person for public queries
Name 120567 0
Ms Rebecca Hahn
Address 120567 0
HLRI WA
Level 1
Harry Perkins Institute of Medical Research
5 Robin Warren Drive
MURDOCH WA 6150
Country 120567 0
Australia
Phone 120567 0
+61 439975860
Fax 120567 0
Email 120567 0
rebecca.hahn@health.wa.gov.au
Contact person for scientific queries
Name 120568 0
Ms Rebecca Hahn
Address 120568 0
HLRI WA
Level 1
Harry Perkins Institute of Medical Research
5 Robin Warren Drive
MURDOCH WA 6150
Country 120568 0
Australia
Phone 120568 0
+61 439975860
Fax 120568 0
Email 120568 0
rebecca.hahn@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
confidential


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
No additional documents have been identified.