Myocardial Blood Flow by PET and N-13 Ammonia During Regadenoson vs Adenosine Stress

Coronary Artery Disease Clinical Trial

Official title:

Quantification of Myocardial Blood Flow by Positron Emission Tomography and N-13 Ammonia During Regadenoson vs Adenosine Stress

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01370265
• Other study ID #: 10-006377
• Status: Completed
• Phase: N/A
• First received: June 6, 2011
• Last updated: September 3, 2013
• Start date: February 2011
• Est. completion date: June 2012

Study information

• Verified date: September 2013
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Blockage of the heart arteries (coronary artery disease) can lead to angina (chest pain), heart attacks, heart failure, and/or death. Positron emission tomography (PET) stress myocardial perfusion imaging (MPI) is a powerful tool to help identify blockages in the coronary arteries. During the PET MPI test, a drug is given to mimic the effects of exercise on the heart. The study was done to measure blood flow to the heart using two similar drugs approved to mimic the effects of exercise on the heart in people during a heart stress test. The first drug, called adenosine, has been approved for this use for several decades. The second drug, called regadenoson, was approved in 2008. The investigators were looking at whether the increase in blood flow to the heart with the newer drug (regadenoson) was similar to the increase in blood flow with the older drug (adenosine). This information is important for the use of these drugs in patients and for interpreting the blood flow values.

Description:

The hypothesis for this study was that Regadenoson will produce a very similar degree of maximal hyperemia (increased blood flow) as adenosine, the other vasodilator agent. There were only 2 days on study for each subject.

On Day 1 of the study, subjects were interviewed and had a physical exam, including a resting 12-lead electrocardiogram (ECG) to exclude evidence of silent ischemia or myocardial infarction, and other cardiovascular disorders. Subjects were instructed to have a light meal at least 4 hours prior to the PET MPI. Subjects were instructed to abstain from caffeine-containing products for 24 hours prior to the PET scan. Day 1 of the study occurred less than or equal to 4 weeks of Day 2.

On Day 2 of the study, each subject underwent three PET N-13 ammonia (10-20 mCi) dynamic emission acquisitions: resting, regadenoson (0.4 mg/5 mL IV), and adenosine (140 microgram/kg/min; order of regadenoson vs adenosine was randomized according to subject's birth year), and three transmission acquisitions for attenuation correction. Each emission acquisition was separated by 50 min to allow for radioactive decay. At the end of the drug infusions, subjects were monitored for 5-30 min. Based on the known short biological half-lives of these stress agents, the pharmacologic effects of each drug should have dissipated by the time the next drug was administered.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: June 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 30 Years and older

Eligibility

Inclusion Criteria:

• Healthy male and female volunteers over the age of 30.

• Written informed consent will be obtained from each subject.

• Each subject will undergo a history and physical examination

Exclusion Criteria:

• Any cardiovascular or pulmonary symptoms or exam findings

• History of low blood pressure (< 90/50 mmHg)

• Prior cardiac history

• History of hypertension

• History of hyperlipidemia

• History of diabetes mellitus

• History of asthma or chronic obstructive pulmonary disease

• Weight of > 450 pounds

• Chronic kidney disease

• Other serious illness such as cancer

• Current smoking

• Medication use (with the exception of acetaminophen, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and thyroid hormone replacement)

• Illicit drug use

• Prior allergic reaction to adenosine, regadenoson, or aminophylline

• Pregnancy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Regadenoson
Regadenoson (0.4 mg/5 ml IV) was administered intravenously over 10 seconds, followed immediately by saline flush.
• Adenosine
Adenosine (140 µg/kg/min) was administered intravenously over 6 minutes.
• N-13 ammonia
Ammonia N-13 Injection is a radioactive diagnostic agent for Positron Emission Tomography (PET) indicated for diagnostic PET imaging of the myocardium under rest or pharmacologic stress conditions to evaluate myocardial perfusion in patients with suspected or existing coronary artery disease. The N-13 ammonia used in the study was synthesized by the Mayo Cyclotron Facility as per routine institutional clinical protocol.

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Astellas Pharma Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Hyperemic Myocardial Blood Flow (MBF)	MBF is the rate of blood supplied to the myocardium, or heart muscle. Hyperemic MBF is the rate of myocardial blood flow in the heart muscle during either regadenoson or adenosine stress. Myocardial blood flow was calculated using commercial software (PMOD Technologies, version 2.4).; The Hyperemic MBF was measured approximately 4 hours after arrival in the PET unit.	Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit	No
Secondary	Resting Global MBF and Resting Segmental MBF	MBF is the rate of blood supplied to the myocardium, or heart muscle. Global Myocardial blood flow was calculated using commercial software (PMOD Technologies, version 2.4).; Regional MBFs were calculated using commercial software (PMOD Technologies, version 2.4). After the apical and basal slices of the left ventricular myocardium were chosen, the software automatically defined 4 myocardial regions of interest (segments) in the apical planes.	Day 2, approximately 35 minutes after arrival in positron emission tomography (PET) unit	No
Secondary	Global Cardiac Flow Rate	Cardiac Flow Rate was calculated using the equation: hyperemic MBF/resting MBF.	Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit	No
Secondary	Hyperemic Segmental MBF	Regional MBFs were calculated using commercial software (PMOD Technologies, version 2.4). After the apical and basal slices of the left ventricular myocardium were chosen, the software automatically defined 4 myocardial regions of interest (segments) in the apical planes.; The hyperemic MBF was measured approximately 4 hours after arrival in the PET unit, depending on the randomization.	Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit	No
Secondary	Segmental CFR	CFR was calculated using the equation: hyperemic MBF/resting MBF.	Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit	No
Secondary	Heart Rate (Beats Per Minute (BPM))	The resting heart rate was measured approximately 35 minutes after arrival in the PET unit. The hyperemic heart rate was measured approximately 4 hours after arrival in the PET unit, depending on the randomization.	Day 2, approximately 35 minutes and approximately 4 hours after arrival in the PET unit	No
Secondary	Hyperemic Blood Pressure (mmHg)	Blood pressure was measured approximately 4 hours after arrival in the PET unit, depending on the randomization.	Day 2, approximately 4 hours after arrival in the PET unit	No