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

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Panithaya Chareonthaitawee, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01370265
First received: June 6, 2011
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
Coronary Artery Disease
Drug: Regadenoson
Drug: Adenosine
Drug: N-13 ammonia

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Quantification of Myocardial Blood Flow by Positron Emission Tomography and N-13 Ammonia During Regadenoson vs Adenosine Stress

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Global Hyperemic Myocardial Blood Flow (MBF) [ Time Frame: Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Resting Global MBF and Resting Segmental MBF [ Time Frame: Day 2, approximately 35 minutes after arrival in positron emission tomography (PET) unit ] [ Designated as safety issue: No ]

    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.


  • Global Cardiac Flow Rate [ Time Frame: Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit ] [ Designated as safety issue: No ]
    Cardiac Flow Rate was calculated using the equation: hyperemic MBF/resting MBF.

  • Hyperemic Segmental MBF [ Time Frame: Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit ] [ Designated as safety issue: No ]

    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.


  • Segmental CFR [ Time Frame: Day 2, approximately 4 hours after arrival in positron emission tomography (PET) unit ] [ Designated as safety issue: No ]
    CFR was calculated using the equation: hyperemic MBF/resting MBF.

  • Heart Rate (Beats Per Minute (BPM)) [ Time Frame: Day 2, approximately 35 minutes and approximately 4 hours after arrival in the PET unit ] [ Designated as safety issue: No ]
    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.

  • Hyperemic Blood Pressure (mmHg) [ Time Frame: Day 2, approximately 4 hours after arrival in the PET unit ] [ Designated as safety issue: No ]
    Blood pressure was measured approximately 4 hours after arrival in the PET unit, depending on the randomization.


Enrollment: 12
Study Start Date: February 2011
Study Completion Date: June 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Regadenoson, then Adenosine
Regadenoson (0.4 mg/5 ml IV) was administered intravenously over 10 seconds, followed immediately by saline flush and N-13 ammonia (10-20 MCi) injection and an additional saline flush in the first intervention period. Adenosine (140 μg/kg/min) was administered intravenously over 6 minutes in the second intervention period (after washout period). Three minutes after the start of adenosine infusion, N-13 ammonia (10-20 mCi) was administered.
Drug: Regadenoson
Regadenoson (0.4 mg/5 ml IV) was administered intravenously over 10 seconds, followed immediately by saline flush.
Other Name: Lexiscan
Drug: Adenosine
Adenosine (140 μg/kg/min) was administered intravenously over 6 minutes.
Other Name: Adenoscan
Drug: 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.
Active Comparator: Adenosine, then Regadenoson
Adenosine (140 μg/kg/min) was administered intravenously over 6 minutes in the first intervention period. Three minutes after the start of adenosine infusion, N-13 ammonia (10-20 mCi) was administered. After a washout period, Regadenoson (0.4 mg/5 ml IV) was administered intravenously over 10 seconds, followed immediately by saline flush and N-13 ammonia (10-20 MCi) injection and an additional saline flush in the second intervention period.
Drug: Regadenoson
Regadenoson (0.4 mg/5 ml IV) was administered intravenously over 10 seconds, followed immediately by saline flush.
Other Name: Lexiscan
Drug: Adenosine
Adenosine (140 μg/kg/min) was administered intravenously over 6 minutes.
Other Name: Adenoscan
Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01370265

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Astellas Pharma Inc
Investigators
Principal Investigator: Panithaya Chareonthaitawee, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Panithaya Chareonthaitawee, Consultant, Associate Professor, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01370265     History of Changes
Other Study ID Numbers: 10-006377
Study First Received: June 6, 2011
Results First Received: October 6, 2012
Last Updated: September 3, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Regadenoson (Lexiscan)
PET N-13 ammonia imaging
Myocardial Blood Flow (MBF)
Regadenoson Stress

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Adenosine
Regadenoson
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Cardiovascular Agents
Vasodilator Agents
Adenosine A2 Receptor Antagonists
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014