PET/MR-P: Development of a PET-MR Myocardial Perfusion Examination Using Regadenoson

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01779869
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 28.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The objective for this pilot study is to develop an optimized, clinically usable myocardial PET-MR perfusion protocol and to determine which of all data potentially available should be acquired for a clinical myocardial perfusion examination. Hypothesis: The hypothesis is that high resolution, high sensitivity DCE MRI could replace the rest PET myocardial perfusion imaging, significantly decreasing examination time and patient radiation dose while maintaining the comprehensive reference-quality PET myocardial stress perfusion coverage.

The primary outcome will be comparison of diagnostic accuracy of each combination of imaging to detect clinically significant coronary artery stenosis (≥70% diameter stenosis).

Condition or Disease	Intervention/Treatment	Phase
Ischemic Heart Disease	Drug: Regadenoson	Phase 4

Detailed Description

Simultaneous acquisition PET-MRI is a new technology that has the potential to significantly impact diagnostic patient care. It combines high signal resolution MRI anatomic imaging and PET biological measurements, with the added benefit of radiation dose reduction in comparison to PET-CT. As the incidence of false positive SPECT-MPI studies secondary to attenuation artifact is relatively high and MRI coverage of the left ventricular myocardium is limited, it is likely that one of the immediate applications of PET-MRI technology is myocardial ischemia assessment.

PET has long been considered the noninvasive reference standard for myocardial perfusion. However, delayed contrast enhanced (DCE) MRI is very sensitive for infarct detection. Indeed, both PET and MR imaging have the potential to provide comprehensive whole heart ischemia and infarct detection.

PET-MR technology, with its ability to obtain simultaneous perfusion information via both PET and MRI, has the potential to obtain multiple, possibly redundant, data sets. On the other hand, it also has the potential to combine the best of both techniques to provide a highly robust examination that is both shorter and of lower radiation dose than the standard myocardial PET perfusion examination. Optimization of a protocol is necessary to develop a comprehensive protocol without redundancy. Because of its single injection capability, regadenoson is ideally suited to a protocol that will assess and employ dual-modality myocardial perfusion data collection.

It is expected that the best candidates for PET-MR myocardial perfusion imaging will likely be a) patients whose body habitus suggests that their SPECT-MPI examination would be limited by attenuation artifact -- women with large breasts and patients (usually men) with abdominal obesity and/or b) patients who may have a smaller region of ischemia that might be missed on an MRI examinations with limited perfusion coverage.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Development of a PET-MR Myocardial Perfusion Examination Using Regadenoson
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Single group assignment - imaging All patients will undergo PET-MR myocardial perfusion imaging during rapid intravenous administration of 0.4 mg regadenoson.

Drug: Regadenoson; Regadenoson 400 micrograms will be administered in a single IV bolus (<10 seconds) via an antecubital cannula and followed by 5 mL of saline flush. 10-20 seconds after the regadenoson is administered, 10 mCi of 13N-ammonia as a bolus, and 0.075 mmol/Kg of gadobenate dimeglumine MR contrast agent at a rate of 5 mL/sec followed by a 15 mL normal saline flush will be administered simultaneous, each into an antecubital vein, and a 15 min list-mode PET acquisition will be acquired simultaneously with the MR perfusion imaging.; Other Names: Lexiscan

Outcome Measures

Primary Outcome Measures

1. Diagnostic Accuracy of Cardiac PET/MRI Examination [PET/MRI imaging was performed within 10 days after SPECT-MPI examination]

   The accuracy of the cardiac PET and cardiac MR examination components of the PET/MRI, and the accuracy of the combined PET/MR examination, for ischemic heart disease will be compared to the accuracy of cardiac SPECT in patients who have had ICA as "truth" or the reference standard. To assess the accuracy of an abbreviated PET/MR examination, an additional accuracy analysis was made using only the stress PET perfusion imaging and the MR LGE data sets. The accuracy of this combined data set was also determined with ICA as "truth" or the reference standard. Accuracy is calculated as % difference = (experimental - true) x 100%.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients who have had a clinically ordered rest/regadenoson single-isotope SPECT-MPI study within 10 days prior to cardiac PET-MRI examination

• Reversible perfusion abnormalities on SPECT imaging in at least 2 contiguous myocardial segments

• Patients for whom standard of care coronary ICA is planned

Exclusion Criteria:

• An clinical event (ie; worsening angina pectoris or myocardial infarction) occuring after the SPECT-MPI and before the cardiac MRI examination

• Myocardial revascularization occuring after the SPECT-MPI and before the cardiac MRI examination

• Contraindications to MR imaging (pacemaker, brain aneurysm clips, shrapnel, etc.)

• Renal insufficiency (GFR < 60 mL/min/1.73m2)

• Allergy or other contraindication to gadolinium-based MR contrast agent

• Second or third degree atrioventricular (AV) block

• Active asthma

• Seizures

• Current hypotension (<100/60)

• Current hypertension (>160/90)

• Pregnancy

• Breast feeding

• Use of caffeine, nicotine or over the counter cold medicines within 12 hours of the cardiac PET-MRI examination

• Use of the medication dipyridamole within 48 hrs of the cardiac PET-MRI examination

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Clinical Imaging Research at Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Astellas Pharma US, Inc.

Investigators

• Principal Investigator: Pamela K Woodard, MD, BA, Washington University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pamela Woodard, MD, Director of Center for Clinical Imaging Research (CCIR), Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01779869
• Other Study ID Numbers: PET/MR-Perfusion
• First Posted: Jan 30, 2013
• Last Update Posted: Jun 15, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Pamela Woodard, MD, Director of Center for Clinical Imaging Research (CCIR), Washington University School of Medicine: PET MR myocardial perfusion imaging
• Additional relevant MeSH terms: Heart Diseases; Myocardial Ischemia; Coronary Artery Disease; Regadenoson

Study Results

Participant Flow

Arm/Group Title	Single Group Assignment - Imaging
Arm/Group Description	All patients will undergo PET-MR myocardial perfusion imaging during rapid intravenous administration of 0.4 mg regadenoson. Regadenoson: Regadenoson 400 micrograms will be administered in a single IV bolus (<10 seconds) via an antecubital cannula and followed by 5 mL of saline flush. 10-20 seconds after the regadenoson is administered, 10 mCi of 13N-ammonia as a bolus, and 0.075 mmol/Kg of gadobenate dimeglumine MR contrast agent at a rate of 5 mL/sec followed by a 15 mL normal saline flush will be administered simultaneous, each into an antecubital vein, and a 15 min list-mode PET acquisition will be acquired simultaneously with the MR perfusion imaging.
Period Title: Overall Study
STARTED	16
COMPLETED	14
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Single Group Assignment - Imaging
Arm/Group Description	All patients will undergo PET-MR myocardial perfusion imaging during rapid intravenous administration of 0.4 mg regadenoson. Regadenoson: Regadenoson 400 micrograms will be administered in a single IV bolus (<10 seconds) via an antecubital cannula and followed by 5 mL of saline flush. 10-20 seconds after the regadenoson is administered, 10 mCi of 13N-ammonia as a bolus, and 0.075 mmol/Kg of gadobenate dimeglumine MR contrast agent at a rate of 5 mL/sec followed by a 15 mL normal saline flush will be administered simultaneous, each into an antecubital vein, and a 15 min list-mode PET acquisition will be acquired simultaneously with the MR perfusion imaging.
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55 (12.4)
Sex: Female, Male (Count of Participants)
Female	9 56.3%
Male	7 43.8%
Positive cardiac SPECT stress test (2 contiguous segments) (Count of Participants)
Count of Participants [Participants]	16 100%
Scheduled to undergo ICA (Count of Participants)
Count of Participants [Participants]	16 100%

Outcome Measures

1. Primary Outcome

Title	Diagnostic Accuracy of Cardiac PET/MRI Examination
Description	The accuracy of the cardiac PET and cardiac MR examination components of the PET/MRI, and the accuracy of the combined PET/MR examination, for ischemic heart disease will be compared to the accuracy of cardiac SPECT in patients who have had ICA as "truth" or the reference standard. To assess the accuracy of an abbreviated PET/MR examination, an additional accuracy analysis was made using only the stress PET perfusion imaging and the MR LGE data sets. The accuracy of this combined data set was also determined with ICA as "truth" or the reference standard. Accuracy is calculated as % difference = (experimental - true) x 100%.
Time Frame	PET/MRI imaging was performed within 10 days after SPECT-MPI examination

Outcome Measure Data

Analysis Population Description

Patients who completed the full PET-MR myocardial perfusion examination

Arm/Group Title	Single Group Assignment - Imaging
Arm/Group Description	All patients will undergo PET-MR myocardial perfusion imaging during rapid intravenous administration of 0.4 mg regadenoson. Regadenoson: Regadenoson 400 micrograms will be administered in a single IV bolus (<10 seconds) via an antecubital cannula and followed by 5 mL of saline flush. 10-20 seconds after the regadenoson is administered, 10 mCi of 13N-ammonia as a bolus, and 0.075 mmol/Kg of gadobenate dimeglumine MR contrast agent at a rate of 5 mL/sec followed by a 15 mL normal saline flush will be administered simultaneous, each into an antecubital vein, and a 15 min list-mode PET acquisition will be acquired simultaneously with the MR perfusion imaging.
Measure Participants	16
SPECT Accuracy	50
MR Accuracy	64
PET Accuracy	61
Combined PET/MR Accuracy	64
Abbreviated PET/MR	64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Single Group Assignment - Imaging
	Comments	Significance testing between the diagnostic accuracy of SPECT and PET, and SPECT and MR, and SPECT and PET/MR was performed by using chi square test. A P value < 0.05 was considered significant.
	Type of Statistical Test	Superiority
	Comments	Accuracy was assessed compared to an imaging reference standard.
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	24 hours after imaging
Arm/Group Title	Single Group Assignment - Imaging
Arm/Group Description	All patients will undergo PET-MR myocardial perfusion imaging during rapid intravenous administration of 0.4 mg regadenoson. Regadenoson: Regadenoson 400 micrograms will be administered in a single IV bolus (<10 seconds) via an antecubital cannula and followed by 5 mL of saline flush. 10-20 seconds after the regadenoson is administered, 10 mCi of 13N-ammonia as a bolus, and 0.075 mmol/Kg of gadobenate dimeglumine MR contrast agent at a rate of 5 mL/sec followed by a 15 mL normal saline flush will be administered simultaneous, each into an antecubital vein, and a 15 min list-mode PET acquisition will be acquired simultaneously with the MR perfusion imaging.
All Cause Mortality
	Single Group Assignment - Imaging
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Serious Adverse Events
	Single Group Assignment - Imaging
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Single Group Assignment - Imaging
	Affected / at Risk (%)	# Events
Total	0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.