A Study of Regadenoson in Subjects Undergoing Stress Myocardial Perfusion Imaging (MPI) Using Multidetector Computed Tomography (MDCT) Compared to Single Photon Emission Computed Tomography (SPECT)
Study Details
Study Description
Brief Summary
The purpose of this study is to compare Multidetector Computed Tomography (MDCT) and Single Photon Emission Computed Tomography (SPECT) stress myocardial perfusion imaging (MPI) with regadenoson in order to detect the presence or absence of reversible defects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
All participants will be randomized to one of two imaging sequences: rest/stress SPECT on Day 1 followed by stress/rest MDCT on Day 2 or stress/rest MDCT on Day 1 followed by rest/stress SPECT on Day 2. All stress scans will involve the injection of regadenoson as the pharmacologic stress agent.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Single Photon Emission Computed Tomography (SPECT) Resting SPECT imaging was performed prior to regadenoson stress SPECT imaging. Imaging was conducted with one of two radiotracers (99mTc sestamibi or tetrofosmin). Regadenoson 0.4 mg was administered prior to stress SPECT as a single bolus injection. |
Drug: regadenoson
Administered by intravenous bolus.
Other Names:
Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin
Administered by intravenous infusion
Other Names:
Radiation: Contrast
Administered by intravenous infusion.
Procedure: Single Photon Emission Computed Tomography
Procedure/Surgery
Procedure: Multidetector Computed Tomography
Procedure/Surgery
|
| Experimental: Multidetector Computed Tomography (MDCT) Multidetector Computed Tomography (MDCT), composed of CCTA and regadenoson CTP. Regadenoson stress CTP was performed prior to rest CCTA/CTP imaging. Regadenoson 0.4 mg was administered prior to stress CTP as a single bolus injection. The rest CCTA/CTP was performed at least 30 minutes after completion of the stress CTP, after resolution of any symptoms brought on by the regadenoson infusion and after the participant's heart rate had returned to baseline. |
Drug: regadenoson
Administered by intravenous bolus.
Other Names:
Radiation: technetium Tc99m sestamibi /technetium Tc99m tetrafosmin
Administered by intravenous infusion
Other Names:
Radiation: Contrast
Administered by intravenous infusion.
Procedure: Single Photon Emission Computed Tomography
Procedure/Surgery
Procedure: Multidetector Computed Tomography
Procedure/Surgery
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Reversible Defects [Day 1 and Day 2]
The number of reversible defects categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from the 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of 2 or more segments with reversible defects, excluding segment 17.
Secondary Outcome Measures
- Overall Image Quality of Scans by Modality and Reviewer [Day 1 and Day 2]
Overall image quality was assessed by three independent blinded readers for each modality (single photon emission computed tomography (SPECT) and multidetector computed tomography (MDCT)). Image quality was rated on a 4-point scale as either excellent, good, fair or poor at rest using SPECT and MDCT and under stress using regadenoson SPECT and regadenoson stress computed tomography perfusion (CTP).
- Number of Participants With Reversible Defects in the Left Anterior Descending Coronary Artery (LAD) [Day 1 and Day 2]
The number of reversible defects in the LAD categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17.
- Number of Participants With Reversible Defects in the Right Coronary Artery (RCA) [Day 1 and Day 2]
The number of reversible defects in the RCA categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17.
- Number of Participants With Reversible Defects in the Left Circumflex Coronary Artery (LCX) [Day 1 and Day 2]
The number of reversible defects in the LCX categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17.
- Number of Participants With Fixed Defects [Day 1 and Day 2]
Using the 17-segment scoring system, a segment scored above 1 (i.e., 2 to 4) and equal at rest and stress was counted as having a fixed defect. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake.
- Percentage of Participants With Two or More Ischemic Segments on SPECT, But Less on CT [Day 1 and Day 2]
Using SPECT as the reference standard, the false negative percentage was calculated as the percentage of participants with two or more ischemic segments on SPECT, but less on CT.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male subjects must be ≥ 45 years of age
-
Female subjects must be ≥ 50 years of age
-
Subject has met at least one of the following three criteria:
-
has a suspected (clinical impression) or known diagnosis of coronary artery disease (CAD) with typical angina that has been referred from nuclear cardiology lab schedule or cardiac computed tomography (CT) schedule
-
has stable symptoms with possible elective catheterization procedure scheduled and where further imaging may be beneficial;
-
has known CAD from a previous invasive coronary angiography (ICA) performed more than 12 weeks prior to screening who now present with new cardiac symptoms
-
Subject has been referred for a clinically indicated myocardial perfusion imaging procedure or Cardiac CT procedure for suspected moderate or high risk CAD
-
Subject must abstain from eating and drinking 30 minutes prior and 30 minutes post study drug administration
-
Subject must abstain from smoking 3 hours prior and 8 hours post study drug administration
-
Subject must abstain from any intake of methylxanthine-containing foods and beverages within 12 hours prior to Day 1 visit through the Day 3 Follow-Up Visit, as these foods may alter regadenoson effects. Subject is able to safely abstain from theophylline use for 12 hours prior to study drug administration
Exclusion Criteria:
-
Subject is concurrently participating in another drug study or has received an investigational drug within 30 days prior to Screening
-
Subject has a history of a clinically significant illness (other than CAD), medical condition, or laboratory abnormality, which would preclude participation in the study
-
Subject has renal dysfunction demonstrated by a glomerular filtration rate (GFR) < 45 mL/min (calculated using Cockroft-Gault formula Note: Subjects with a GFR 45-60 mL/min will undergo a hydration procedure
-
Female subject who is pregnant, lactating or of childbearing potential that refuses to use a medically acceptable form of contraception until the Telephone Follow up Visit is complete
-
Female subject has a positive pregnancy test prior to randomization
-
Subject has a history of second or third degree heart block or sinus node dysfunction unless the subject has a functioning pacemaker
-
Subject has symptomatic hypotension (temporary and reversible conditions that no longer exist are allowed)
-
Subject is allergic or intolerant to aminophylline, nitroglycerin or metoprolol
-
Subject is allergic or intolerant to regadenoson or any of its excipients
-
Subject is unable or unwilling to comply with the procedure schedule
-
Subject has previously enrolled in this study or was enrolled in another regadenoson study sponsored by Astellas
-
Subject has atrial fibrillation or significant arrhythmias which may result in decreased image quality for the imaging studies (CT and SPECT)
-
Subject has high heart rate (> 65 beats per minute) and contra-indications to administer beta-blockers (severe chronic obstructive pulmonary disease (COPD) or asthma, second and third degree atrioventricular block)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sutter Roseville Medical Center | Roseville | California | United States | 95661 |
| 2 | Harbor UCLA Medical Center | Torrance | California | United States | 90502 |
| 3 | Cardiovascular Research Center of South Florida | Miami | Florida | United States | 33173 |
| 4 | Baptist Hospital of Miami | Miami | Florida | United States | 33176 |
| 5 | Midwest Cardiology Associates, P.C. | Overland Park | Kansas | United States | 66029 |
| 6 | Maine Research Associates | Auburn | Maine | United States | 04210 |
| 7 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 8 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 9 | Berkshire Medical Center | Pittsfield | Massachusetts | United States | 01201 |
| 10 | Henry Ford Health System | Detroit | Michigan | United States | 48202 |
| 11 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
Sponsors and Collaborators
- Astellas Pharma Inc
Investigators
- Study Director: Senior Medical Director, Astellas Pharma Global Development
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 3606-CL-2001
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Sequence 1: SPECT - MDCT | Sequence 2: MDCT - SPECT |
|---|---|---|
| Arm/Group Description | Day 1: a rest Single Photon Emission Computed Tomography (SPECT) and a regadenoson stress SPECT procedure. Day 2: a regadenoson stress Computed Tomography Perfusion (CTP) and a rest Coronary Computed Tomography Angiography (CCTA)/CTP procedure. Regadenoson 0.4 mg was administered prior to each stress procedure as a single bolus injection. | Day 1: a regadenoson stress CTP and a rest CCTA/CTP procedure. Day 2: a rest SPECT and a regadenoson stress SPECT procedure. Regadenoson 0.4 mg was administered prior to each stress procedure as a single bolus injection. |
| Period Title: Overall Study | ||
| STARTED | 63 | 61 |
| Randomized + 1 Stress Scan | 57 | 61 |
| COMPLETED | 55 | 60 |
| NOT COMPLETED | 8 | 1 |
Baseline Characteristics
| Arm/Group Title | Sequence 1: SPECT - MDCT | Sequence 2: MDCT - SPECT | Total |
|---|---|---|---|
| Arm/Group Description | Day 1: a rest Single Photon Emission Computed Tomography (SPECT) and a regadenoson stress SPECT procedure. Day 2: a regadenoson stress Computed Tomography Perfusion (CTP) and a rest Coronary Computed Tomography Angiography (CCTA)/CTP procedure. Regadenoson 0.4 mg was administered prior to each stress procedure as a single bolus injection. | Day 1: a regadenoson stress CTP and a rest CCTA/CTP procedure. Day 2: a rest SPECT and a regadenoson stress SPECT procedure. Regadenoson 0.4 mg was administered prior to each stress procedure as a single bolus injection. | Total of all reporting groups |
| Overall Participants | 57 | 61 | 118 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60.8
(9.19)
|
62.3
(9.41)
|
61.6
(9.29)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
18
31.6%
|
15
24.6%
|
33
28%
|
| Male |
39
68.4%
|
46
75.4%
|
85
72%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
52
91.2%
|
54
88.5%
|
106
89.8%
|
| Black or African American |
2
3.5%
|
5
8.2%
|
7
5.9%
|
| Asian |
3
5.3%
|
2
3.3%
|
5
4.2%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Not Hispanic or Latino |
37
64.9%
|
41
67.2%
|
78
66.1%
|
| Hispanic or Latino |
20
35.1%
|
20
32.8%
|
40
33.9%
|
Outcome Measures
| Title | Number of Participants With Reversible Defects |
|---|---|
| Description | The number of reversible defects categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from the 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of 2 or more segments with reversible defects, excluding segment 17. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set, defined as all randomized patients with interpretable SPECT and CTP scans as determined by at least two of the three blinded readers. |
| Arm/Group Title | CTP: 0 - 1 Reversible Defects | CTP: ≥ 2 Reversible Defects | CTP: All Reversible Defects |
|---|---|---|---|
| Arm/Group Description | Participants with 0 - 1 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | Participants with ≥ 2 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | All participants as assessed by regadenoson stress computed tomography perfusion (CTP). |
| Measure Participants | 85 | 25 | 110 |
| SPECT: 0-1 Reversible defects |
84
147.4%
|
16
26.2%
|
100
84.7%
|
| SPECT: ≥ 2 Reversible defects |
1
1.8%
|
9
14.8%
|
10
8.5%
|
| SPECT: All Reversible defects |
85
149.1%
|
25
41%
|
110
93.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CTP: 0 - 1 Reversible Defects, CTP: ≥ 2 Reversible Defects, CTP: All Reversible Defects |
|---|---|---|
| Comments | Analysis of agreement rate based on participants with 0 -1 and ≥ 2 reversible defects according to SPECT. Agreement is defined as the proportion of participants who had the same status from SPECT and MDCT, averaged across those with 2 or more reversible defects and those without, where SPECT is the reference standard. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Predefined noninferiority criterion: If the lower boundary of the 95% CI was within 0.15 of 0.78, MDCT would be determined to be noninferior to SPECT. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Agreement rate |
| Estimated Value | 0.87 | |
| Confidence Interval |
(2-Sided) 95% 0.77 to 0.97 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.051 |
|
| Estimation Comments | ||
| Title | Overall Image Quality of Scans by Modality and Reviewer |
|---|---|
| Description | Overall image quality was assessed by three independent blinded readers for each modality (single photon emission computed tomography (SPECT) and multidetector computed tomography (MDCT)). Image quality was rated on a 4-point scale as either excellent, good, fair or poor at rest using SPECT and MDCT and under stress using regadenoson SPECT and regadenoson stress computed tomography perfusion (CTP). |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set. |
| Arm/Group Title | SPECT: Reviewer 1 | SPECT: Reviewer 2 | SPECT: Reviewer 3 | MDCT: Reviewer 1 | MDCT: Reviewer 2 | MDCT: Reviewer 3 |
|---|---|---|---|---|---|---|
| Arm/Group Description | Analysis of image quality of single photon emission computed tomography (SPECT) images performed by SPECT Reviewer 1. | Analysis of image quality of single photon emission computed tomography (SPECT) images performed by SPECT Reviewer 2. | Analysis of image quality of single photon emission computed tomography (SPECT) images performed by SPECT Reviewer 3. | Analysis of image quality of multidetector computed tomography (MDCT) images performed by MDCT Reviewer 1. | Analysis of image quality of multidetector computed tomography (MDCT) images performed by MDCT Reviewer 2. | Analysis of image quality of multidetector computed tomography (MDCT) images performed by MDCT Reviewer 3. |
| Measure Participants | 110 | 110 | 110 | 110 | 110 | 110 |
| Rest: Excellent |
89
156.1%
|
25
41%
|
83
70.3%
|
30
NaN
|
40
NaN
|
56
NaN
|
| Rest: Good |
16
28.1%
|
53
86.9%
|
23
19.5%
|
56
NaN
|
37
NaN
|
43
NaN
|
| Rest: Fair |
4
7%
|
31
50.8%
|
4
3.4%
|
23
NaN
|
33
NaN
|
11
NaN
|
| Rest: Poor |
1
1.8%
|
1
1.6%
|
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
| Stress: Excellent |
89
156.1%
|
35
57.4%
|
78
66.1%
|
5
NaN
|
15
NaN
|
37
NaN
|
| Stress: Good |
16
28.1%
|
51
83.6%
|
27
22.9%
|
48
NaN
|
24
NaN
|
36
NaN
|
| Stress: Fair |
4
7%
|
24
39.3%
|
5
4.2%
|
56
NaN
|
62
NaN
|
34
NaN
|
| Stress: Poor |
1
1.8%
|
0
0%
|
0
0%
|
1
NaN
|
9
NaN
|
3
NaN
|
| Title | Number of Participants With Reversible Defects in the Left Anterior Descending Coronary Artery (LAD) |
|---|---|
| Description | The number of reversible defects in the LAD categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set where scans were available. |
| Arm/Group Title | CTP: 0 - 1 Reversible Defects | CTP: ≥ 2 Reversible Defects | CTP: All Reversible Defects |
|---|---|---|---|
| Arm/Group Description | Participants with 0 - 1 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | Participants with ≥ 2 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | All participants as assessed by regadenoson stress computed tomography perfusion (CTP). |
| Measure Participants | 90 | 15 | 105 |
| SPECT: 0 - 1 Reversible defects |
90
157.9%
|
11
18%
|
101
85.6%
|
| SPECT: ≥ 2 Reversible defects |
0
0%
|
4
6.6%
|
4
3.4%
|
| SPECT: All Reversible defects |
90
157.9%
|
15
24.6%
|
105
89%
|
| Title | Number of Participants With Reversible Defects in the Right Coronary Artery (RCA) |
|---|---|
| Description | The number of reversible defects in the RCA categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set where scans were available. |
| Arm/Group Title | CTP: 0 - 1 Reversible Defects | CTP: ≥ 2 Reversible Defects | CTP: All Reversible Defects |
|---|---|---|---|
| Arm/Group Description | Participants with 0 - 1 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | Participants with ≥ 2 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | All participants as assessed by regadenoson stress computed tomography perfusion (CTP). |
| Measure Participants | 93 | 5 | 98 |
| SPECT: 0 - 1 Reversible defects |
92
161.4%
|
5
8.2%
|
97
82.2%
|
| SPECT: ≥ 2 Reversible defects |
1
1.8%
|
0
0%
|
1
0.8%
|
| SPECT: All Reversible defects |
93
163.2%
|
5
8.2%
|
98
83.1%
|
| Title | Number of Participants With Reversible Defects in the Left Circumflex Coronary Artery (LCX) |
|---|---|
| Description | The number of reversible defects in the LCX categorized into absence or presence of ischemia (0-1 versus ≥2), as assessed by the central imaging laboratory for both SPECT and MDCT. The 17-segment model for standardized myocardial segmentation was used for myocardial perfusion readings for SPECT and MDCT. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. The median score from 3 blinded readers for each segment was used. If the stress score was ≥ 2 and the rest score was less than the stress score, the segment was counted as having a reversible defect. A participant was classified as ischemic in the presence of ≥ 2 segments with reversible defects, excluding segment 17. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set where scans were available. |
| Arm/Group Title | CTP: 0 - 1 Reversible Defects | CTP: ≥ 2 Reversible Defects | CTP: All Reversible Defects |
|---|---|---|---|
| Arm/Group Description | Participants with 0 - 1 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | Participants with ≥ 2 reversible defects as assessed by regadenoson stress computed tomography perfusion (CTP). | All participants as assessed by regadenoson stress computed tomography perfusion (CTP). |
| Measure Participants | 92 | 13 | 105 |
| SPECT: 0 - 1 Reversible defects |
90
157.9%
|
9
14.8%
|
99
83.9%
|
| SPECT: ≥ 2 Reversible defects |
2
3.5%
|
4
6.6%
|
6
5.1%
|
| SPECT: All Reversible defects |
92
161.4%
|
13
21.3%
|
105
89%
|
| Title | Number of Participants With Fixed Defects |
|---|---|
| Description | Using the 17-segment scoring system, a segment scored above 1 (i.e., 2 to 4) and equal at rest and stress was counted as having a fixed defect. At rest and stress, each segment was scored on a 0 to 4 scale according to the amount of contrast or radiotracer the myocardium in the segment absorbed: 0: normal perfusion 1: slightly reduced contrast/radiotracer uptake 2: moderately reduced contrast/radiotracer uptake 3: severely reduced contrast/radiotracer uptake 4: absent contrast/radiotracer uptake. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of participants analyzed represents the full analysis set. |
| Arm/Group Title | CTP: 0 Fixed Defects | CTP: ≥ 1 Fixed Defects | CTP: All Fixed Defects |
|---|---|---|---|
| Arm/Group Description | Participants with zero fixed defects as assessed by regadenoson stress computed tomography perfusion (CTP). | Participants with ≥ 1 fixed defects as assessed by regadenoson stress computed tomography perfusion (CTP). | All participants as assessed by regadenoson stress computed tomography perfusion (CTP). |
| Measure Participants | 95 | 15 | 110 |
| SPECT: 0 Fixed Defects |
92
161.4%
|
5
8.2%
|
97
82.2%
|
| SPECT: ≥ 1 Fixed Defects |
3
5.3%
|
10
16.4%
|
13
11%
|
| SPECT: All Fixed Defects |
95
166.7%
|
15
24.6%
|
110
93.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CTP: 0 - 1 Reversible Defects, CTP: ≥ 2 Reversible Defects, CTP: All Reversible Defects |
|---|---|---|
| Comments | Analysis of specificity based on participants with no fixed defects according to SPECT. Specificity is defined as a proportion of true negatives that are correctly identified, using SPECT as the reference standard. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Specificity |
| Estimated Value | 0.95 | |
| Confidence Interval |
(2-Sided) 95% 0.90 to 0.99 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.022 |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CTP: 0 - 1 Reversible Defects, CTP: ≥ 2 Reversible Defects, CTP: All Reversible Defects |
|---|---|---|
| Comments | Analysis of sensitivity based on participants with ≥ 1 fixed defect according to SPECT. Sensitivity is the proportion of true positives that are correctly identified using SPECT as the reference standard. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Sensitivity |
| Estimated Value | 0.77 | |
| Confidence Interval |
(2-Sided) 95% 0.54 to 1.00 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.117 |
|
| Estimation Comments | ||
| Title | Percentage of Participants With Two or More Ischemic Segments on SPECT, But Less on CT |
|---|---|
| Description | Using SPECT as the reference standard, the false negative percentage was calculated as the percentage of participants with two or more ischemic segments on SPECT, but less on CT. |
| Time Frame | Day 1 and Day 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with two or more reversible defects. |
| Arm/Group Title | SPECT + MDCT |
|---|---|
| Arm/Group Description | Participants underwent both a rest and stress SPECT series and a rest and stress MDCT series. |
| Measure Participants | 10 |
| Number [percentage of participants] |
10
17.5%
|
Adverse Events
| Time Frame | Treatment-emergent adverse events (TEAEs) were defined as adverse events observed from the time of administration of regadenoson to 24 hours after last study drug administration within each modality, i.e. from Day 1 to Day 3. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analysis Set composed of all randomized patients who received at least 1 dose of regadenoson. | |||
| Arm/Group Title | SPECT | MDCT | ||
| Arm/Group Description | Resting SPECT imaging was performed prior to regadenoson stress SPECT imaging. Imaging was conducted with one of two radiotracers (99mTc sestamibi or tetrofosmin). Regadenoson 0.4 mg was administered prior to stress SPECT as a single bolus injection. | Multidetector Computed Tomography (MDCT), composed of CCTA and regadenoson CTP. Regadenoson stress CTP was performed prior to rest CCTA/CTP imaging. Regadenoson 0.4 mg was administered prior to stress CTP as a single bolus injection. The rest CCTA/CTP was performed at least 30 minutes after completion of the stress CTP, after resolution of any symptoms brought on by the regadenoson infusion and after the participant's heart rate had returned to baseline. | ||
All Cause Mortality |
||||
| SPECT | MDCT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| SPECT | MDCT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/117 (0.9%) | 0/116 (0%) | ||
| Gastrointestinal disorders | ||||
| Gastritis | 1/117 (0.9%) | 0/116 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| SPECT | MDCT | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/117 (45.3%) | 59/116 (50.9%) | ||
| Cardiac disorders | ||||
| Angina pectoris | 4/117 (3.4%) | 9/116 (7.8%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 9/117 (7.7%) | 6/116 (5.2%) | ||
| General disorders | ||||
| Chest discomfort | 11/117 (9.4%) | 9/116 (7.8%) | ||
| Nervous system disorders | ||||
| Headache | 15/117 (12.8%) | 23/116 (19.8%) | ||
| Dizziness | 11/117 (9.4%) | 6/116 (5.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 13/117 (11.1%) | 10/116 (8.6%) | ||
| Vascular disorders | ||||
| Flushing | 18/117 (15.4%) | 26/116 (22.4%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
Results Point of Contact
| Name/Title | Senior Medical Director, Medical Affairs |
|---|---|
| Organization | Astellas Scientific and Medical Affairs, Inc. / Astellas Pharma Global Development, Inc. |
| Phone | |
| ClinicalTrials.Disclosure@us.astellas.com |
- 3606-CL-2001