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Trial registered on ANZCTR


Registration number
ACTRN12617000368336
Ethics application status
Approved
Date submitted
3/03/2017
Date registered
10/03/2017
Date last updated
14/08/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Left Ventricular Pressure as a Treatment Target in Patients with Myocardial Infarction.
Scientific title
Effect of Nitrates and Frusemide on Left Ventricular Pressure in Patients with ST-Segment Elevation Myocardial Infarction Following Primary Percutaneous Coronary Intervention.
Secondary ID [1] 291274 0
None.
Universal Trial Number (UTN)
U1111-1193-7740
Trial acronym
LVEDP
Linked study record
None.

Health condition
Health condition(s) or problem(s) studied:
ST-segment elevation myocardial infarction. 302213 0
Condition category
Condition code
Cardiovascular 301818 301818 0 0
Coronary heart disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There is observational evidence that patients with high left ventricular end diastolic pressure (LVEDP) post ST-segment elevation myocardial infarction (STEMI) have higher mortality and re-admission rates but there are no prospective studies that have targeted LVEDP reduction after opening the infarct related artery. In order to design a prospective trial with LVEDP as the treatment target, dose of nitrates needs to be calculated that can cause a reasonable reduction in LVEDP without causing a significant drop in the systemic blood pressure. Thus, the aim of this acute hemodynamic study is to find a dose of nitrate in conjunction with a single bolus of frusemide that reduces LVEDP without causing symptomatic drop in the systemic blood pressure. We aim to enroll 20 patients in our study (Intervention group=10, Control group=10). All patients will have left heart catheterization performed and LVEDP measured immediately after primary percutaneous coronary intervention (PCI) as is standard practice in our institution. Patients with LVEDP greater than 20 mmHg will be enrolled to our study. The patients in the intervention arm will have intravenous administration of frusemide 40mg bolus plus escalating doses of IV glyceryl trinitrate (GTN) during simultaneous measurement of pressure in their left ventricular cavity. We will administer 100mcg GTN intravenously and administer further 100mcg boluses each minute to a maximum of 1000mcg. The study will terminate when there is a drop in either arterial pressure or LVEDP by 20% or if 1000 mcg is reached (over 10 mins) without any demonstrable effect on LVEDP or systemic blood pressure.
We will also perform echocardiogram simultaneously and measure mitral inflow pulse wave Doppler, mitral annular velocities (E/E' ratios), pulmonary venous pulse wave Doppler and pulmonary artery systolic pressures at baseline and after the last dose of GTN.
Intervention code [1] 297288 0
Treatment: Drugs
Comparator / control treatment
The 10 patients in the control arm will have standard treatment for ST-segment elevation myocardial infarction. They will be recruited to the control arm If their LVEDP is greater than 20 mmHg after the intervention to the infarct related artery. These patients will be administered 10 mls of normal saline every minute for next 10 minutes with simultaneous measurement of LVEDP and systolic blood pressure (10 readings over 10 minutes). No trial medication will be administered to this group. We will also perform echocardiogram and measure mitral inflow pulse wave Doppler, mitral annular velocities (E/E' ratios), pulmonary venous pulse wave Doppler and pulmonary artery systolic pressures at baseline and after 10 minutes and will note the changes in these echocardiographic parameters over the 10 minute period.
Control group
Active

Outcomes
Primary outcome [1] 301233 0
1- Dose of GTN needed to cause > 20% reduction in LVEDP. (The LVEDP will be measured directly via placement of a catheter in the left ventricular cavity).
Timepoint [1] 301233 0
Within 1 hour after administration of the drugs.
Primary outcome [2] 301376 0
2- Dose of GTN causing significant drop in systemic blood pressure (Systolic BP < 100 mmHg). The systemic blood pressure will be measured noninvasively from the left arm.
Timepoint [2] 301376 0
Within 1 hour after administration of the drugs.
Secondary outcome [1] 332069 0
1- Dose of GTN causing any significant side effects (e.g. Headache, > 20% increase in heart rate lasting > 5 minutes, > 20% drop in blood pressure lasting > 5 minutes.
a- Headache: It will be assessed subjectively before and after administration of GTN.
b- Heart rate will be monitored invasively.
c- The systemic blood pressure will be measured noninvasively from the left arm during the administration of GTN.
Timepoint [1] 332069 0
Within 1 hour after administration of the drugs.
Secondary outcome [2] 337857 0
The total drop in LVEDP in the intervention arm versus the control arm.
Timepoint [2] 337857 0
Within 1 hour after administration of the trial medications/normal saline.
Secondary outcome [3] 337858 0
The total drop in the systolic blood pressure in the intervention arm versus the control arm.
Timepoint [3] 337858 0
Within 1 hour after administration of the trial medications/normal saline.

Eligibility
Key inclusion criteria
1- Patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.
2- Left ventricular end diastolic pressure > 20 mmHg.
3- Systemic blood pressure > 100 mmHg.
4- No known hypersensitivity or adverse reaction to nitrates or frusemide.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1- Age < 18 years.
2- Cardiogenic shock.
3- Electrical instability requiring intervention.
4- Coronary revascularisation not performed.
5- Pulmonary oedema requiring open label diuretics or nitrates.
6- Renal impairment requiring dialysis

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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)
We aim to enroll 20 patients with ST-segment elevation myocardial infarction (STEMI) to our study (Intervention=10, Control=10). The inclusion criteria will be an LVEDP greater than 20 mmHg after the intervention to the infarct related artery. The patients presenting during the working hours (08:00 to 18:00) will be enrolled to the intervention arm and the after-hours (18:00 to 08:00) will be recruited to the control arm.
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
This is a phase 1 dose escalation study, Therefore, no blinding or masking will be performed.
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
We estimated that our treatment will result in a reduction of LVEDP from 26+/- 5mmHg to 17mmHg with alpha 0.05 and power 80%. There will be no reduction in the LVEDP in the control arm. Therefore, we will require 20 subjects (10 in each group).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
14/03/2017
Actual
3/04/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
20
Accrual to date
10
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 7559 0
John Hunter Hospital - New Lambton
Recruitment postcode(s) [1] 15451 0
2305 - New Lambton

Funding & Sponsors
Funding source category [1] 295731 0
Hospital
Name [1] 295731 0
Cardiovascular Department John Hunter Hospital
Country [1] 295731 0
Australia
Primary sponsor type
Hospital
Name
Cardiovascular Department John Hunter Hospital
Address
Cardiovascular Department John Hunter Hospital Newcastle NSW 2305.
Country
Australia
Secondary sponsor category [1] 294578 0
None
Name [1] 294578 0
Address [1] 294578 0
Country [1] 294578 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297033 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 297033 0
Lookout road New Lambton heights NSW 2305.
Ethics committee country [1] 297033 0
Australia
Date submitted for ethics approval [1] 297033 0
15/02/2017
Approval date [1] 297033 0
07/03/2017
Ethics approval number [1] 297033 0
17/02/15/3.02

Summary
Brief summary
For this acute hemodynamic study, we will measure pressure within the main pumping chamber of the heart (the left ventricle) with a plastic tube (called catheter) after treating the heart attack. In the intervention group, we will give increasing doses of a medication (Glyceryl trinitrate) through the drip for 10 minutes if there are no contraindications or concerns and will simultaneously measure the pressure within the main pumping chamber. Patients will also be given 40 mg of a fluid medication (frusemide). In the control group, pressure in the main pumping chamber will be measured for 10 minutes but no trial medication will be administered.
The aim of this study is to find a dose of these medications that will reduce pressure within the main pumping chamber of the heart without affecting blood pressure or causing any side effects. These medications are routinely used during all the angiography and stenting procedures but have never been used to reduce the pressure within the heart.
Trial website
None.
Trial related presentations / publications
None.
Public notes
None.

Contacts
Principal investigator
Name 72774 0
Prof Andrew Boyle
Address 72774 0
Cardiovascular Department John Hunter Hospital, Lookout road New Lambton Heights NSW 2305.
Country 72774 0
Australia
Phone 72774 0
+61249124205
Fax 72774 0
+61249214210
Email 72774 0
[email protected]
Contact person for public queries
Name 72775 0
Andrew Boyle
Address 72775 0
Cardiovascular Department John Hunter Hospital, Lookout road New Lambton Heights NSW 2305.
Country 72775 0
Australia
Phone 72775 0
+61249124205
Fax 72775 0
+61249214210
Email 72775 0
[email protected]
Contact person for scientific queries
Name 72776 0
Andrew Boyle
Address 72776 0
Cardiovascular Department John Hunter Hospital, Lookout road New Lambton Heights NSW 2305.
Country 72776 0
Australia
Phone 72776 0
+61249124205
Fax 72776 0
+61249214210
Email 72776 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
SourceTitleYear of PublicationDOI
EmbaseTargeting elevated left ventricular end-diastolic pressure following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction - a phase one safety and feasibility study.2020https://dx.doi.org/10.1177/2048872618819657
N.B. These documents automatically identified may not have been verified by the study sponsor.