Integrated Dual Exercise and Lexiscan Positron Emission Tomography: IDEALPET

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01109992
• Collaborator: (none)
• Enrollment: 43
• Location: 1
• Arms: 2
• Duration (Months): 76.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This is a single-center study of subjects undergoing clinically indicated heart scans for evaluation of known or suspected heart disease. We will also include 10 healthy subjects without known heart disease. We would like to study stress testing of the heart using exercise and a medication called regadenoson. Imaging of the heart will be performed.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Exercise plus Regadenoson (Lexercise); Drug: Regadenoson (Lexiscan)	Phase 4

Detailed Description

Regadenoson is stress agent approved by the FDA for use with myocardial perfusion imaging with technetium-99m single photon emission computed tomography (SPECT) in patients that are unable to exercise adequately. We would like to study Regadenoson in conjunction with Exercise Rubidium-82 positron emission tomography myocardial perfusion imaging (PET MPI). Regadenoson is not approved by FDA for use with Rubidium-82 PET MPI. Also, we would like to study a novel stress protocol of Regadenoson combined with symptom limited exercise stress (not FDA approved).

The objectives of this study are to assess the tolerability and safety of combined symptom limited exercise stress test with Lexiscan (Lexercise PET) compared to Lexiscan alone (Lexiscan PET), to assess image quality of Lexercise compared to Lexiscan PET and to compare relative and absolute myocardial perfusion imaging with Lexercise compared to Lexiscan PET to identify CAD.

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Integrated Dual Exercise and Lexiscan PET: IDEAL PET
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Jun 6, 2017
• Actual Study Completion Date: Jun 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Regadenoson (Lexiscan) Regadenoson Rubidium-82 Positron Emission Tomography	Drug: Regadenoson (Lexiscan); Regadenoson Rubidium-82 Positron Emission Tomography
Experimental: Exercise + Regadenoson (Lexercise) Exercise plus Regadenoson (Lexercise) Rubidium-82 Positron Emission Tomography	Drug: Exercise plus Regadenoson (Lexercise); Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography; Other Names: Exercise plus Lexiscan

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability of Combined Exercise and Regadenoson Stress [Day of the research scan during the stress test]

   Count of subjects with ischemic ECG changes is reported Count of subjects with systolic blood pressure decrease > 20 mm Hg is reported Count of subjects with abnormal serum troponin T levels is reported Radiation dose to the staff will be measured using personal dosimeters after the Lexiscan as well as the Lexercise PET study.

Secondary Outcome Measures

1. Image Quality: Heart to Liver Ratio of Counts [Week 1 (day of the clinical scan), and Week 2 (day of the research scan)]

   Sub-diaphragmatic activity: Heart to Liver Ratio was measured on the rubidium-82 and N-13 ammonia scans. Since this measure is a ratio it has no units. Mean and Standard Deviation of Ratio is reported for each group. This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.

2. Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET [Week 1 (day of the clinical scan), and Week 2 (day of the research scan)]

   Left ventricular ejection fraction (LVEF) at stress was measured at Stress scan 1 (regadenoson) and Stress scan 2 (regadenoson or exercise + regadenoson). This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.

3. Peak Stress Myocardial Blood Flow [Week 1 (day of the clinical scan), and Week 2 (day of the research scan)]

   Myocardial Blood Flow Measured at Peak Hyperemia With Regadenoson or Immediately After Exercise + Regadenoson This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age > 18 years

• Clinically indicated N-13 ammonia PET study or ten healthy volunteers

• Known coronary artery disease (prior percutaneous coronary intervention, prior coronary artery bypass surgery or Q wave MI on ECG) or intermediate to high pretest likelihood of CAD

• Able to exercise on a treadmill

• Able and willing to provide informed consent to participate in the study

Exclusion Criteria:

• Contraindications to exercise stress testing such as, unstable angina, known severe left main coronary artery stenosis, severe heart failure, uncontrolled arrhythmias, symptomatic hypotension or severe hypertension (systolic blood pressure < 90 or > 200 mmHg, respectively), or > 1st degree atrioventricular block in the absence of a functioning pacemaker.

• Subject requires emergent cardiac medical intervention or catheterization after the clinical study.

• Documented myocardial infarction (MI) ≤ 30 days prior to enrollment.

• History of percutaneous coronary intervention (PCI) ≤ 4weeks prior to enrollment.

• History of coronary artery bypass graft (CABG) ≤ 8 weeks prior to enrollment.

• History of heart transplantation.

• Allergy or intolerance to aminophylline or regadenoson

• Known severe or oxygen dependent bronchoconstrictive or bronchospastic lung disease [e.g., asthma, wheezing, chronic obstructive pulmonary disease (COPD), etc.].

• Severe LV dysfunction, with ejection fraction of < 30%

• Serious non-cardiac medical illness (e.g., disseminated malignancy, severe neurological dysfunction at time of baseline PET study) or a social situation which will preclude research study participation

• History of Seizures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Womens' Hospital	Boston	Massachusetts	United States	02421

Sponsors and Collaborators

• Brigham and Women's Hospital

Investigators

• Principal Investigator: Sharmila Dorbala, MBBS, Brigham and Women's Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 12, 2016

More Information

Publications

• Camici PG, Crea F. Coronary microvascular dysfunction. N Engl J Med. 2007 Feb 22;356(8):830-40. Review.
• Chow BJ, Ananthasubramaniam K, dekemp RA, Dalipaj MM, Beanlands RS, Ruddy TD. Comparison of treadmill exercise versus dipyridamole stress with myocardial perfusion imaging using rubidium-82 positron emission tomography. J Am Coll Cardiol. 2005 Apr 19;45(8):1227-34.
• Chow BJ, Beanlands RS, Lee A, DaSilva JN, deKemp RA, Alkahtani A, Ruddy TD. Treadmill exercise produces larger perfusion defects than dipyridamole stress N-13 ammonia positron emission tomography. J Am Coll Cardiol. 2006 Jan 17;47(2):411-6.
• Di Carli MF, Hachamovitch R. New technology for noninvasive evaluation of coronary artery disease. Circulation. 2007 Mar 20;115(11):1464-80. Review.
• El Fakhri G, Sitek A, Guérin B, Kijewski MF, Di Carli MF, Moore SC. Quantitative dynamic cardiac 82Rb PET using generalized factor and compartment analyses. J Nucl Med. 2005 Aug;46(8):1264-71.
• Klocke FJ, Baird MG, Lorell BH, Bateman TM, Messer JV, Berman DS, O'Gara PT, Carabello BA, Russell RO Jr, Cerqueira MD, St John Sutton MG, DeMaria AN, Udelson JE, Kennedy JW, Verani MS, Williams KA, Antman EM, Smith SC Jr, Alpert JS, Gregoratos G, Anderson JL, Hiratzka LF, Faxon DP, Hunt SA, Fuster V, Jacobs AK, Gibbons RJ, Russell RO; American College of Cardiology; American Heart Association Task Force on Practice Guidelines; American Society for Nuclear Cardiology. ACC/AHA/ASNC guidelines for the clinical use of cardiac radionuclide imaging--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging). Circulation. 2003 Sep 16;108(11):1404-18.

• Responsible Party: Sharmila Dorbala, MBBS, Director, Nuclear Cardiology, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01109992
• Other Study ID Numbers: BWH
• First Posted: Apr 23, 2010
• Last Update Posted: Oct 25, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Sharmila Dorbala, MBBS, Director, Nuclear Cardiology, Brigham and Women's Hospital: coronary artery disease; exercise; regadenoson; positron emission tomography
• Additional relevant MeSH terms: Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Regadenoson

Study Results

Participant Flow

Recruitment Details	43 subjects consented for the study and 41 subjects completed the study. One subject did not come for the study procedures. One subject could not cooperate with imaging and was moving during the rest scan. Regadenoson scan was not performed.

Arm/Group Title	Regadenoson	Exercise + Regadenoson
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson Rubidium-82 Positron Emission Tomography	Exercise plus Regadenoson Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson: Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography
Period Title: Overall Study
STARTED	11	32
Subjects Enrolled	11	32
COMPLETED	11	30
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Regadenoson	Exercise + Regadenoson	Total
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson: Regadenoson Rubidium-82 Positron Emission Tomography	Exercise plus Regadenoson Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson: Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography	Total of all reporting groups
Overall Participants	11	30	41
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66 (11)	54 (15)	57 (15)
Sex: Female, Male (Count of Participants)
Female	3 27.3%	14 46.7%	17 41.5%
Male	8 72.7%	16 53.3%	24 58.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 6.7%	2 4.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 18.2%	4 13.3%	6 14.6%
White	9 81.8%	22 73.3%	31 75.6%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	2 6.7%	2 4.9%
Region of Enrollment (Count of Participants)
United States	11 100%	30 100%	41 100%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability of Combined Exercise and Regadenoson Stress
Description	Count of subjects with ischemic ECG changes is reported Count of subjects with systolic blood pressure decrease > 20 mm Hg is reported Count of subjects with abnormal serum troponin T levels is reported Radiation dose to the staff will be measured using personal dosimeters after the Lexiscan as well as the Lexercise PET study.
Time Frame	Day of the research scan during the stress test

Outcome Measure Data

Analysis Population Description

Radiation dose to staff was not measured due to logistical difficulties.Three subjects had blood pressure changes in the Regadenoson (Lexiscan) arm; 3 subjects showed ischemic ECG changes in the exercise + regadenoson (Lexercise) arm; and, none of the subjects showed abnormal troponin levels.

Arm/Group Title	Regadenoson (Lexiscan)	Exercise + Regadenoson (Lexercise)
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson (Lexiscan): Regadenoson Rubidium-82 Positron Emission Tomography.	Exercise plus Regadenoson (Lexercise) Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson (Lexercise): Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography
Measure Participants	11	30
Count of ischemic ECG changes	0 0%	3 10%
Count of subjects systolic blood pressure decrease	3 27.3%	0 0%
Count of subjects with abnormal troponin	0 0%	0 0%

2. Secondary Outcome

Title	Image Quality: Heart to Liver Ratio of Counts
Description	Sub-diaphragmatic activity: Heart to Liver Ratio was measured on the rubidium-82 and N-13 ammonia scans. Since this measure is a ratio it has no units. Mean and Standard Deviation of Ratio is reported for each group. This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time Frame	Week 1 (day of the clinical scan), and Week 2 (day of the research scan)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Regadenoson (Lexiscan)	Exercise + Regadenoson (Lexiscan)
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson (Lexiscan): Regadenoson Rubidium-82 Positron Emission Tomography. No adverse events	Exercise plus Regadenoson (Lexiscan) Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson (Lexercise): Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography No adverse events
Measure Participants	11	30
Stress Scan 1	1.23 (0.55)	1.11 (0.58)
Stress Scan 2	1.25 (0.57)	1.37 (0.82)

3. Secondary Outcome

Title	Changes in Left Ventricular Function With Dual Exercise and Regadenoson PET
Description	Left ventricular ejection fraction (LVEF) at stress was measured at Stress scan 1 (regadenoson) and Stress scan 2 (regadenoson or exercise + regadenoson). This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time Frame	Week 1 (day of the clinical scan), and Week 2 (day of the research scan)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Regadenoson (Lexiscan)	Exercise + Regadenoson (Lexercise)
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson (Lexiscan): Regadenoson Rubidium-82 Positron Emission Tomography. No adverse events	Exercise plus Regadenoson (Lexercise) Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson (Lexercise): Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography No adverse events
Measure Participants	11	30
Stress 1 Scan	58 (15)	60 (14)
Stress 2 Scan	59 (15)	62 (14)

4. Secondary Outcome

Title	Peak Stress Myocardial Blood Flow
Description	Myocardial Blood Flow Measured at Peak Hyperemia With Regadenoson or Immediately After Exercise + Regadenoson This was measured on the clinical scan and on the research scan which were performed about 2 weeks apart in most subjects.
Time Frame	Week 1 (day of the clinical scan), and Week 2 (day of the research scan)

Outcome Measure Data

Analysis Population Description

Myocardial blood flow could not be accurately measured in one subject from each arm. Therefore we report information on 10/11 subjects in Regadenoson arm and 29/30 subjects in the Exercise + Regadenoson arm.

Arm/Group Title	Regadenoson (Lexiscan)	Exercise + Regadenoson (Lexiscan)
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson (Lexiscan): Regadenoson Rubidium-82 Positron Emission Tomography. No adverse events	Exercise plus Regadenoson (Lexiscan) Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson (Lexercise): Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography No adverse events
Measure Participants	10	29
Stress 1 Scan	1.82 (0.73)	2.04 (0.58)
Stress 2 Scan	1.85 (0.85)	2.34 (0.82)

Adverse Events

Time Frame	Adverse events were collected on the day of the research study which was in week 2 for most patients.
Arm/Group Title	Regadenoson (Lexiscan)		Exercise + Regadenoson (Lexiscan)
Arm/Group Description	Regadenoson Rubidium-82 Positron Emission Tomography Regadenoson (Lexiscan): Regadenoson Rubidium-82 Positron Emission Tomography		Exercise plus Regadenoson (Lexiscan) Rubidium-82 Positron Emission Tomography Exercise plus Regadenoson (Lexercise): Standard Bruce exercise stress test with regadenoson injection at maximal stress with Rubidium-82 Positron Emission Tomography
All Cause Mortality
	Regadenoson (Lexiscan)		Exercise + Regadenoson (Lexiscan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/30 (0%)
Serious Adverse Events
	Regadenoson (Lexiscan)		Exercise + Regadenoson (Lexiscan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/30 (0%)
Other (Not Including Serious) Adverse Events
	Regadenoson (Lexiscan)		Exercise + Regadenoson (Lexiscan)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/30 (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.