Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000727640
Ethics application status
Approved
Date submitted
17/06/2014
Date registered
8/07/2014
Date last updated
7/08/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Haemodynamic effects of Milrinone in patients with heart failure and preserved ejection fraction (HFPEF)
Scientific title
Haemodynamic effects of Milrinone in patients with heart failure and preserved ejection fraction (HFPEF)
Secondary ID [1] 284820 0
NA
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart failure 292206 0
Condition category
Condition code
Cardiovascular 292540 292540 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Following initial rest and exercise evaluation during Right Heart Catheterization (RHC), patients will be randomly allocated (by envelope) to receive either a standard loading dose of Intravenous (IV) milrinone (50mcg/kg over 10 mins) or placebo. This will be a single dose.
Rest and exercise haemodynamic and echocardiographic studies (as above) will be repeated after a further 10 minutes following the administration of the IV Milrinone.

Following baseline measures, subjects will supine perform symptom-limited supine cycling at incremental levels of 0.3, 0.6, 1.0 and 1.5Watt/kg each for 3 minutes (exercise will not be performed if the resting RHC unexpectedly demonstrates severe pulmonary hypertension PA systolic>60mmHg). The test will be stopped when the patient experiences limiting dyspnoea or other limiting symptoms.
Intervention code [1] 289613 0
Treatment: Drugs
Comparator / control treatment
Randomized study with normal Saline as the placebo.
Control group
Placebo

Outcomes
Primary outcome [1] 292408 0
Invasively measure haemodynamics (right heart catheterization and arterial line) at rest and during exercise in patients with presumed HFPEF and to repeat these measures after random allocation to milrinone or placebo. Arterial and mixed venous blood gas samples will be taken at rest and peak exercise
The primary end-point will be the change in pulmonary capillary wedge pressure during exercise.
Timepoint [1] 292408 0
Arterial and mixed venous blood gas samples will be taken at rest and peak exercise during Right Heart Catheterization (RHC), 10 minutes following the administration of IV Milrinone.

This will also be assessed following the administration of placebo
Secondary outcome [1] 308882 0
Secondary end-points will include: pulmonary artery pressures taken via RHC.
Timepoint [1] 308882 0
Pulmonary Artery Pressures will be taken 10 minutes post administration of IV Milrinone at rest and during exercise.
This outcome will also be assessed following the administration of placebo

Eligibility
Key inclusion criteria
Adults greater than or equal to 18 years of age, AND
Symptoms of HF (NYHA II-III) AND
Normal ejection fraction (LVEF equal to and more than 45%) with evidence of diastolic dysfunction as prescribed by ESC Working Group 15 (resting PCWP more than 12; E/e’ more than 15 or Eand e prime more than 8 and
and NT-BNP more than 220)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Other cause for dyspnoea including moderate or severe valvular HD and pulmonary hypertension with PVR more than 4 Wood Units
Body mass index (BMI) more than 35 kg/m2
History of stress-induced syncope or ventricular tachycardia during exercise
Unstable coronary artery disease
Symptoms and signs of congestive heart failure at rest (NYHA IV)
Unable to perform exercise test

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Calculations and statistics will be performed using SPSS v19. Variables that approximated a normal distribution will be summarised as mean plus and minus standard deviation, and groups compared using T-Tests or RM-ANOVA as appropriate. Non-normal variables will be summarised as median and first and third quartiles (Q1, Q3), and groups compared using Mann-Whitney Rank sum tests with exact inference.

In recent studies in HFPEF patients show that during low level exercise the PCWP rises from 14 plus or minus 6 to 32 plus or minus 6mmHg. We hypothesize that milrinone will reduce the exercise PCWP by 30%. In order to test this hypothesis with power=0.8 and significance level of p<0.05 we will require n=7 per group. To account for study drop-out (in particular due to the identification of unexpected severe PHTn) we aim to recruit a total of 20 patients.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/07/2014
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
14
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 8312 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 289433 0
Hospital
Name [1] 289433 0
Alfred Health
Country [1] 289433 0
Australia
Primary sponsor type
Hospital
Name
Alfred Health
Address
Alfred Health
Commercial Road
Melbourne
3004
Victoria
Country
Australia
Secondary sponsor category [1] 288121 0
None
Name [1] 288121 0
Address [1] 288121 0
Country [1] 288121 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291191 0
Alfred Hospital Ethics and research committee
Ethics committee address [1] 291191 0
Alfred Health
Commercial Road
Melbourne
3004
Victoria
Ethics committee country [1] 291191 0
Australia
Date submitted for ethics approval [1] 291191 0
26/05/2014
Approval date [1] 291191 0
23/07/2014
Ethics approval number [1] 291191 0
248/14

Summary
Brief summary
Invasively measure haemodynamics (right heart catheterization and arterial line) at rest and during exercise (Ex 1) in patients with presumed HFPEF and to repeat these measures after random allocation to milrinone or placebo
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49278 0
Prof David Kaye
Address 49278 0
Alfred Health
Commerical Road
Melbourne
3004
Victoria
Country 49278 0
Australia
Phone 49278 0
+61,3,90763263
Fax 49278 0
Email 49278 0
[email protected]
Contact person for public queries
Name 49279 0
Ms Fiona Tweedley
Address 49279 0
Alfred Health
Commerical Road
Melbourne
3004
Victoria
Country 49279 0
Australia
Phone 49279 0
+61,3,90762978
Fax 49279 0
Email 49279 0
[email protected]
Contact person for scientific queries
Name 49280 0
Prof David Kaye
Address 49280 0
Alfred Health
Commerical Road
Melbourne
3004
Victoria
Country 49280 0
Australia
Phone 49280 0
+61,3,90763263
Fax 49280 0
Email 49280 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
No additional documents have been identified.