None listed
Conditions
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.
Interventions
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.
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.
Sponsors
The Heart foundation
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients with STEMI and LVEDP equal to/greater than 20 mmHg after successful primary or rescue percutaneous coronary intervention.
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.
Outcome results
None listed