A Validation Study of Nitroglycerin Induced Acute Drop of Pd/Pa (NTG-Pd/Pa) in Clinical Practice

Hyperemia with adenosine was an elemental process in FFR examination. Adenosine injection will induce some discomfort, and increase cost expenditure. Nitroglycerine will induce an acute drop of Pd/Pa, and this lowest Pd/Pa was determined as NTG-Pd/Pa. NTG-Pd/Pa has a linear relationship with FFR value and has a good diagnostic accuracy to predict FFR≤0.80 in our recent study. There is only one prospective study report on the relationship between NTG-Pd/Pa and FFR. In this study, we aim to evaluate the safety of NTG-Pd/Pa, the repeatability and dose-response of this novel index. Furthermore, we will investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 and Resting full-cycle ratio≤0.89 as ischemic threshold respectively.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Heart Disease; Hypotension Symptomatic
• Intervention / Treatment: Diagnostic test: Nitroglycerine

Detailed Description

Fractional flow reserve (FFR) is defined as the ratio of mean distal pressure (distal to the target lesion, Pd）to mean proximal pressure (aortic pressure, Pa) in the coronary artery(Pd/Pa) while the maximal hyperemic flow is achieved. Nowadays, FFR-guided PCI is highly recommended for the assessment of physiologic ischemia in intermediate coronary lesions. However, hyperemia with adenosine was an elemental process in FFR examination. Adenosine injection will induce some discomfort, and increase cost expenditure. Based on the clinical and physiologic outcome study, a lot of non-hyperemic indexes had been proposed, and adenosine injection could be waived. Whereas, these novel physiologic indexes are limited to the proprietary software of each vendor, curtailing clinical application. Intracoronary nitroglycerin injection was needed before each FFR assessment. Nitroglycerine will induce an acute drop of Pd/Pa, and this lowest Pd/Pa was determined as NTG-Pd/Pa. NTG-Pd/Pa has a linear relationship with FFR value and has a good diagnostic accuracy to predict FFR≤0.80 in our recent study. There is only one prospective study report on the relationship between NTG-Pd/Pa and FFR. In this study, we aim to evaluate the safety of NTG-Pd/Pa, the repeatability and dose-response of this novel index. Furthermore, we will investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 and Resting full-cycle ratio≤0.89 as ischemic threshold respectively.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Taiwan
  • Hsinchu, Taiwan, 300
    • Recruiting
    • National Taiwan University Hospital Hsin-Chu Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients who had intermediate lesion over the coronary artery and eligible for FFR examination

Description

Inclusion Criteria:

• Eligible for FFR examination

Exclusion Criteria:

• Hypersensitivity to adenosine or nitroglycerine
• Severe Valvular aortic stenosis
• Resting heart rate less than 50 beats per minutes
• Systolic blood pressure less than 100 mmHg or diastolic blood pressure less than 40 mmHg
• exposure to PDE-5 inhibitors within 48 hours.
• Recent intracranial hemorrhage or brain injury

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Repeatability group 1; The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 100 mcg nitroglycerine injection, with a time interval of 3 minutes apart.	Diagnostic test: Nitroglycerine; We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.
Repeatability group 2; The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 200 mcg nitroglycerine injection, with a time interval of 3 minutes apart.	Diagnostic test: Nitroglycerine; We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.
Repeatability group 3; The patient with systolic blood pressure above 120 mmHg, who will receive a repeatability test with 200mcg, then another 300 mcg nitroglycerine injection, with a time interval of 3 minutes apart.	Diagnostic test: Nitroglycerine; We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.
pressure-recommended doses of NTG; The patient with systolic blood pressure above 100 mmHg, who will receive the nitroglycerine injection with the dose of recommendation, adjusted according to the blood pressure.	Diagnostic test: Nitroglycerine; We aim to test the repeatability of NTG-Pd/Pa with different dosages of nitroglycerine injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The repeatability and dose response of NTG-Pd/Pa	Comparing the difference of NTG-Pd/Pa value after various dosage of nitroglycerine injection in the same coronary lesion	10 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiac event	MACE including target lesion failure, target vessel failure, target vessel-related myocardial infarction, and cardiac death	2 years
Diagnostic accuracy of NTG-Pd/Pa 1	Investigate the diagnostic accuracy of NTG-Pd/Pa, with FFR≤0.8 as ischemic threshold	30 minutes
Diagnostic accuracy of NTG-Pd/Pa 2	Investigate the diagnostic accuracy of NTG-Pd/Pa, with RFR≤0.89 as ischemic threshold	30 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitroglycerine related adverse events	Including symptomatic hypotension or severe headache	1 hour

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital Hsin-Chu Branch

Study record dates

Study Major Dates

• Study Start (Anticipated): January 2, 2021
• Primary Completion (Anticipated): February 29, 2024
• Study Completion (Anticipated): February 29, 2024

Study Registration Dates

• First Submitted: January 6, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 7, 2021

Study Record Updates

• Last Update Posted (Actual): January 7, 2021
• Last Update Submitted That Met QC Criteria: January 6, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: NTG-Pd/Pa, Fractional flow reserve, adenosine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Heart Diseases; Coronary Artery Disease; Myocardial Ischemia; Hypotension; Vasodilator Agents; Nitroglycerin
• Other Study ID Numbers: 109-081-E

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No