Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000096257
Ethics application status
Approved
Date submitted
3/11/2017
Date registered
22/01/2018
Date last updated
22/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
The effect of isosorbide mononitrate and frusemide on heart's function after major heart attack.
Scientific title
The Effect of Reduction of End Diastolic Pressure with Isosorbide Mononitrate and frusemide on mortality and infarct size in Acute Myocardial Infarction.
Secondary ID [1] 293150 0
None
Universal Trial Number (UTN)
Trial acronym
The RED PAMI trial.
Linked study record

Health condition
Health condition(s) or problem(s) studied:
ST-segment elevation myocardial infarction (STEMI) 305347 0
Condition category
Condition code
Cardiovascular 304631 304631 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The patients with ST-segment elevation myocardial infarction (STEMI) and elevated left ventricular end diastolic pressure (LVEDP) will be randomised to the intervention and the control arms.
The patients in the intervention group will be commenced on isosorbide moninitrate (ISMN) 30 mg orally daily and frusemide 40mg orally daily during the index hospitalization.
The dose of ISMN will be doubled to 60 mg daily in 2 weeks if patient tolerates it well. The dose of frusemide will be unchanged (i.e. 40 mg orally daily for 3 months).
Total duration of administration of each drug = 3 months.
Intervention adherence: The intervention adherence will be assessed by regular phone calls by the trial coordinator and by pill counting.
Intervention code [1] 299532 0
Treatment: Drugs
Comparator / control treatment
The patients in the control arm will have placebo (microcellulose capsule).
Control group
Placebo

Outcomes
Primary outcome [1] 303859 0
Change in left ventricular end diastolic volume index on cardiac magnetic resonance imaging and echocardiogram from post-myocardial infarction to 3 months.
Timepoint [1] 303859 0
3 months post STEMI.
Secondary outcome [1] 340300 0
Major adverse cardiac events (combination of death, myocardial infarction, stroke and heart failure admission).
The secondary outcomes will be assessed by linking to the patient medical records and the registry of birth, death and marriage. There will also be direct contact with patients and their general practitioners.
Timepoint [1] 340300 0
3 months and 1 year.
Secondary outcome [2] 341931 0
Cardiac magnetic resonance endpoints: Myocardial salvage index.
Timepoint [2] 341931 0
At 3 months.
Secondary outcome [3] 341932 0
Cardiac magnetic resonance endpoints: Change in infarct size.
Timepoint [3] 341932 0
At 3 months.
Secondary outcome [4] 341933 0
Cardiac magnetic resonance endpoints: Change in left ventricular ejection fraction.
Timepoint [4] 341933 0
At 3 months.

Eligibility
Key inclusion criteria
Patients with STEMI and LVEDP equal to/greater than 20 mmHg after successful primary or rescue percutaneous coronary intervention.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1- Inability to informed consent.
2- Patients presenting with cardiogenic shock.
3- Patients requiring cardiopulmonary resuscitation.
4- Any ventricular arrhythmia requiring treatment.
5- Current diagnosis of or treatment for cancer.
6- Current life-threatening condition (other than vascular disease) with life expectancy < 1year.
7- Use of any other investigational device or investigational drug.
8- Patients considered unsuitable to participate by the research team (e.g. owing to medical reasons, laboratory abnormalities, or patient’s unwillingness to comply with all study-related procedures).
9- Severe infection, or any significant trauma (fractures, burns etc.)
10- Pregnancy or lactation.
11- Contraindications to cardiac magnetic resonance scanning – e.g. Pacemakers, intracranial clips or other metal implants or Claustrophobia.
12- History of drug or alcohol abuse within the past 6 months.
13- Angiographically – Multivessel disease with untreated significant stenosis (greater than 70%) in non-infarct related artery or planned future PCI or coronary artery bypass graft surgery. Patients planned for staged PCI during the index admission can be enrolled.
14- Renal impairment with known eGFR < 30 ml/min or maintenance dialysis.
15- Patients taking phosphodiesterase type 5 inhibitors (e.g. sildenafil) as these are contraindicated with nitrates.
16- Patients with any other relative or absolute contraindications to the study drugs.




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)
Immediately following successful PCI, randomization will be performed using the “Randomizer for Clinical Trail” app. This will randomly assign patients in block sizes of 10 to either Group A or Group B, and study drug will be administered according to the protocol. Only the site pharmacist will be unblinded as to which group is active drug and which group is placebo.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be performed using the “Randomizer for Clinical Trail” app. This will randomly assign patients in block sizes of 10 to either Group A or Group B
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
Comparisons will be between the isosorbide mononitrate plus-frusemide-treated and placebo control-treated groups for the primary and secondary outcomes. All analyses will be based on the intention-to-treat principle. Baseline clinical variables and demographics will be summarized for each group. Descriptive summaries of the distributions of continuous baseline variables will be presented in terms of mean ± standard deviation, while discrete variables will be summarized in terms of frequencies and percentages. All p values will be two-sided.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2018
Actual
Date of last participant enrolment
Anticipated
1/02/2019
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
92
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 9336 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 18007 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 297778 0
Hospital
Name [1] 297778 0
John Hunter Hospital
Country [1] 297778 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The Heart foundation
Address
Level 2, 850 Collins Street, Docklands, VIC, 3008
Country
Australia
Secondary sponsor category [1] 296814 0
Other
Name [1] 296814 0
Hunter Medical Research Institute
Address [1] 296814 0
lookout road, New Lambton Heights NSW 2305
Country [1] 296814 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298837 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 298837 0
Ethics Administrative Officer | Research Ethics & Governance Office
Locked Bag 1 New Lambton NSW 2305
Ethics committee country [1] 298837 0
Australia
Date submitted for ethics approval [1] 298837 0
30/05/2017
Approval date [1] 298837 0
11/10/2017
Ethics approval number [1] 298837 0
NSW HREC Reference No: HREC/17/HNE/225

Summary
Brief summary
Rationale: Elevated pressure in the pain pumping chamber of the heart following major heart attack can result in increased mortality and heart failure. However, to date this elevated pressure has not been used as a risk stratification tool following major heart attcak, and there have been no clinical trials directly aimed at its reduction.
The aim of this study is to extend upon our phase 1 study and perform a phase 2 study of isosorbide mononitrate (ISMN) and frusemide administered to the subset of patients with raised pressure in the main pumping chamber of the heart and to see if it results in the clinical benefit.
Overall Design: Randomized controlled trial.
Number of Participants:
Approximately 150 participants will be screened to achieve 92 participants randomly assigned to the intervention or the control arm (46 in each arm).
Intervention Groups and Duration:
Intervention arm: 46 patients, followed up for 12 months.
Control arm: 46 patients, followed up for 12 months.
Possible benefits: Participation in this study may or may not have any direct benefit for the enrolled patients, but it will help us in better understanding of the pressure changes within the heart in the setting of major heart attack and its effects on heart failure and mortality. It will also help us in designing our future research studies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78394 0
Prof Andrew J Boyle
Address 78394 0
Cardiovascular Department, John Hunter Hospital Lookout road, New Lambton height NSW 2305
Country 78394 0
Australia
Phone 78394 0
+61249214205
Fax 78394 0
Email 78394 0
andrew.boyle@newcastle.edu.au
Contact person for public queries
Name 78395 0
Dr Arshad A Khan
Address 78395 0
Cardiovascular Department, John Hunter Hospital Lookout road, New Lambton height NSW 2305
Country 78395 0
Australia
Phone 78395 0
+61430053747
Fax 78395 0
Email 78395 0
arshadkhan@live.com.au
Contact person for scientific queries
Name 78396 0
Dr Arshad A Khan
Address 78396 0
Cardiovascular Department, John Hunter Hospital Lookout road, New Lambton height NSW 2305
Country 78396 0
Australia
Phone 78396 0
+61430053747
Fax 78396 0
Email 78396 0
arshadkhan@live.com.au

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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