The Effect of Sublingual Nitroglycerin on Absolute Coronary Blood Flow (FLOW-NITRO)
The Effect of Sublingual Nitroglycerin on Absolute Coronary Blood Flow: A Randomised, Placebo-controlled, Mechanistic Trial
The goal of this clinical trial is to investigate the effect of sublingual nitroglycerin on absolute coronary blood flow in adult patients undergoing coronary angiography. The main questions it aims to answer are:
- Does sublingual nitroglycerin change absolute coronary blood flow compared to placebo?
- What is the effect of sublingual nitroglycerin on important cardioavascular parameters such as coronary pressure and resistance?
Researchers will compare the sublingual nitroglycerin group to the placebo group to see if nitroglycerin leads to significant changes in coronary blood flow and microvascular function.
Participants will:
- Receive either sublingual nitroglycerin or a placebo during coronary angiography.
- Undergo coronary blood flow measurements before and after the intervention using standardized assessment techniques.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
INTRODUCTION
Nitrates remain a key drug class in the management of angina pectoris due to their capacity to decrease myocardial oxygen demand. Their principle mechanism of action relates to the relaxation of vascular smooth muscle leading to vasodilation. Nitrates are predominately venodilators resulting in a decrease in cardiac preload, left ventricular diastolic pressure, and thus myocardial wall stress and subendocardial compression. However, at low doses, nitrates also trigger arterial and arteriolar dilatation with an eventual reduction in systemic vascular resistance and cardiac afterload at higher doses.
At the coronary level, the direct action of nitrates is thought to be almost exclusively restricted to the epicardial vessels with significant vasodilatation demonstrated in both normal and stenotic epicardial coronary arteries. Furthermore, in a canine model, nitrates have been shown to increase absolute coronary blood. The limited direct effect of nitrates on coronary microcirculation relates to the resistance of arterioles with a diameter <100 μm to their action. However, coronary flow in these smaller vessels may be increased indirectly as decreased left ventricular end-diastolic pressure and wall stress induced by systemic venous dilatation has been shown to increase flow from the epicardium to endocardium.
Despite our understanding of the mechanisms behind the antianginal effects of nitrates, the quantification of their effect on absolute coronary flow has never been demonstrated in humans.
GOAL OF THE STUDY
In the present study, the investigators aim to use continuous thermodilution to asses the impact of sublingual nitroglycerin (NTG) on absolute coronary blood flow when compared with a placebo control.
DESIGN
This is an investigator-initiated, prospective, double-blinded randomised controlled study recruiting patients undergoing diagnostic coronary angiography for suspected angina pectoris from a single centre, and in whom coronary blood flow measurements are part of routine clinical practice, patients will be randomised between sublingual NTG and placebo.
OVERVIEW OF THE STUDY PROTOCOL
Critically, all recruited patients will have any pre-existing vasoactive medications stopped 24 hours before the protocol.
Upon completion of diagnostic coronary angiography, baseline and hyperemic, coronary pressures (Pd and Pa) and resting volumetric blood flow (Qrest) will be assessed by continuous thermodilution. These measurements necessitate the use of a pressure/temperature guidewire and a dedicated infusion catheter. They are performed routinely to evaluate the function of the microcirculation. The measurements are described in details hereunder (see paragraph 'Continuous thermodilution measurements').
During the measurement of resting flow, the patient will be randomised to either the intervention (2 puffs of sublingual NTG at a total dose of 800 µg) or a sublingual placebo by a research nurse. The research nurse will administer the sublingual spray with both the physicians and the patient blinded to patient randomisation. Once administered, continuous thermodilution will be continued for a further 7 minutes to permit enough time to capture any treatment effect as seen in the canine model. It is expected that the protocol, including recording of baseline values, will last ~10 minutes. The same protocol will then be repeated during hyperaemia.
The following parameters will be recorded/calculated at baseline as well as at 1, 3, 5, and 7 minutes post NTG administration, in order to capture the full effect of NTG on both coronary and systemic haemodynamics.
- Absolute coronary blood flow (Q)
- Microvascular resistance (Rµ)
- Epicardial resistance (Repi)
- Total resistance (Rtot)
- Aortic pressure (Pa)
- Distal coronary pressure (Pd)
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Flanders
-
Aalst, Flanders, Belgium, 9300
- OLV Cardiovascular Center Aalst
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Referred for invasive coronary angiography (ICA) for suspected coronary artery disease
Exclusion Criteria:
- ≥1 severe stenosis (defined as a diameter stenosis >70%)
- Clinical signs or symptoms of congestive heart failure
- Severe valvular heart disease requiring either surgical or percutaneous intervention
- History of coronary artery bypass grafting
- Tortuous coronary anatomy in which wire manipulation could be complex
- Significant arrhythmia
- Use of vasoactive medications within 24 hours of coronary angiography
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
2 puffs of sublingual saline
|
2 puffs of sublingual saline
|
|
Experimental: GTN
2 puffs for a total dose of 800 µg
|
2 sublingual puffs for a total dose of 800 µg
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change from baseline in the absolute coronary flow 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Absolute coronary flow will be measured using continuous intracoronary thermodilution
|
10 minutes from the administration of the sublingual intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Change from baseline in the absolute microvascular resistance 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Absolute microvascular resistance will be calculated using absolute coronary flow and distal coronary pressure
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in the absolute epicardial resistance 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Absolute epicardial resistance will be calculated using absolute coronary flow, aortic pressure and distal coronary pressure
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in aortic pressure 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Aortic pressure will be measured using the coronary guiding catheter
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in distal coronary pressure 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Distal coronary pressure will be measured using a standard coronary pressure wire
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in left ventricular end-diastolic pressure 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
LVEDP will be measured using a pigtail catheter at baseline, and at the end of the protocol
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in left ventricular work 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Left ventricular work will be estimated using the systolic pressure-time index (SPTI) derived from the aortic pressure curve.
|
10 minutes from the administration of the sublingual intervention
|
|
Change from baseline in myocardial perfusion 10 minutes after administration of the intervention
Time Frame: 10 minutes from the administration of the sublingual intervention
|
Myocardial perfusion will be estimated using the Buckberg Index.
It will be calculated by dividing the diastolic pressure-time index (i.e.
time of coronary perfusion) by the systolic pressure-time index (i.e.
time of myocardial oxygen demand).
|
10 minutes from the administration of the sublingual intervention
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- OLV2024/037; B1262024000004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.