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A Study to Assess Regadenoson Administration Following an Inadequate Exercise Stress Test as Compared to Regadenoson Alone for Myocardial Perfusion Imaging (MPI) Using Single Photon Emission Computed Tomography (SPECT) (EXERRT)

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ClinicalTrials.gov Identifier: NCT01618669
Recruitment Status : Completed
First Posted : June 13, 2012
Results First Posted : February 8, 2016
Last Update Posted : February 8, 2016
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label)
Condition Coronary Artery Disease (CAD)
Interventions Drug: Regadenoson
Procedure: Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)
Enrollment 1147
Recruitment Details This study was conducted at 49 sites in a total of 3 countries including the United States (44 sites), Argentina (4 sites) and Peru (1 site).
Pre-assignment Details At Baseline, patients meeting all inclusion/exclusion criteria completed single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) while at rest. Participants then underwent a Bruce or modified Bruce exercise protocol; those unable to reach 85% maximum predicted heart rate and/or 5 metabolic equivalents were randomized.
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT myocardial perfusion imaging (MPI). One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Period Title: Overall Study
Started 578 569
Received Treatment 575 567
Completed 544 546
Not Completed 34 23
Reason Not Completed
Lost to Follow-up             1             1
Randomized but Never Received Study Drug             3             2
Adverse Event             16             7
Protocol Violation             5             3
Withdrawal by Subject             9             9
Miscellaneous Reason             0             1
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone Total
Hide Arm/Group Description On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. Total of all reporting groups
Overall Number of Baseline Participants 575 567 1142
Hide Baseline Analysis Population Description
All randomized participants who took at least 1 dose of study drug (Safety Analysis Set).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 575 participants 567 participants 1142 participants
61.9  (11.45) 61.9  (11.19) 61.9  (11.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 575 participants 567 participants 1142 participants
Female
234
  40.7%
239
  42.2%
473
  41.4%
Male
341
  59.3%
328
  57.8%
669
  58.6%
Bruce Exercise Group   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 575 participants 567 participants 1142 participants
Standard Bruce Exercise 448 442 890
Modified Bruce Exercise 90 93 183
[1]
Measure Description:

The Bruce exercise test involves walking on a treadmill while the heart is monitored by an electrocardiograph. The protocol consists of several stages of progressively greater workloads.

The Modified Bruce protocol starts at a lower workload than the standard test and is typically used for elderly or sedentary patients.

Data are reported for all randomized participants with interpretable SPECT scans at all visits as determined by at least 2 of the 3 blinded independent expert readers (full analysis set; 538 and 534 participants in each treatment group respectively).

Maximum Metabolic Equivalents Achieved   [1] 
Mean (Standard Deviation)
Unit of measure:  Metabolic equivalents
Number Analyzed 575 participants 567 participants 1142 participants
5.45  (2.284) 5.37  (2.331) 5.41  (2.307)
[1]
Measure Description:

A metabolic unit used to quantify the intensity of physical activity, which is defined as the ratio of the metabolic rate during exercise to the metabolic rate at rest. One MET corresponds to an energy expenditure of approximately 1 kcal/kg/hour, or an oxygen uptake of 3.5 ml of O2 consumption/kg/hour.

Data are provided for the full analysis set (538 and 534 participants in each treatment group respectively).

1.Primary Outcome
Title Proportion of Participants With Majority Reader Self-agreement in Ischemia Assessment Between First and Second Stress Scans
Hide Description

SPECT scans were reviewed in a blinded fashion by 3 independent expert readers using the 17-segment model for standardized myocardial segmentation. At rest and stress, each segment was scored on a 0 (normal) to 4 (absent contrast/radiotracer uptake) scale by each of the 3 blinded readers according to the amount of contrast or radiotracer the myocardium in the segment absorbed. 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.

The number of segments with reversible defects was categorized as absence (0 - 1 reversible segments) or presence (≥ 2 defects reversible segments) of ischemia.

Each reader was defined as having self-agreement based upon identical categorization of a given participant as absent or present for ischemia for both the initial and second stress visits.

Majority agreement is if at least 2 out of the 3 blinded readers demonstrated self-agreement for a given participant.

Time Frame Day 1 (rest scan and first stress scan) and Day 2 -15 (second stress scan)
Show Outcome Measure DataHide Outcome Measure Data
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Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.92
(0.89 to 0.94)
0.95
(0.93 to 0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regadenoson After Peak Exercise, Regadenoson Alone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments If the lower confidence bound of the 1-sided alpha level of 0.025 of the difference in the proportion of participants with majority reader self-agreement exceeded -0.075, non-inferiority would be demonstrated.
Method of Estimation Estimation Parameter Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.06 to -0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.015
Estimation Comments Difference equals Regadenoson After Peak Exercise minus Regadenoson Alone
2.Secondary Outcome
Title Percentage of Participants With Treatment-emergent Clinically Significant Cardiac Events
Hide Description

A clinically significant cardiac event is defined as:

  • Any of the following events found on the Holter electrocardiogram (ECG)/12-Lead ECG within 1 hour after regadenoson administration:

    • ventricular arrhythmias (sustained ventricular tachycardia, ventricular fibrillation, torsade de pointes, ventricular flutter),
    • ST-T depression (> 2 mm),
    • ST-T elevation (≥1 mm),
    • Atrioventricular (AV) block (2:1 AV block, AV Mobitz I, AV Mobitz II, complete heart block)
    • sinus arrest > 3 seconds in duration

Or

  • a treatment-emergent adverse event (TEAE) per the Medical Dictionary for Regulatory Activities (MedDRA) Standardised MedDRA Queries (SMQ) (Narrow Scope) for myocardial infarction

Or

  • a TEAE preferred term of angina unstable within 24 hours of regadenoson administration.
Time Frame Within 1 hour for ECG events and up to 24 hours for adverse events after administration of regadenoson
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set (all randomized participants who received at least 1 dose of regadenoson study drug)
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 575 544 567 548
Measure Type: Number
Unit of Measure: percentage of participants
Any Event 3.0 0.9 0.5 0.4
Any Holter/12-Lead ECG Abnormality 2.8 0.9 0.5 0.4
Sustained Ventricular Tachycardia 0.0 0.0 0.0 0.0
Ventricular Fibrillation or Ventricular Flutter 0.0 0.0 0.0 0.0
Torsade de Pointes 0.0 0.0 0.0 0.0
ST-T Depression (≥ 2 mm) 2.3 0.6 0.4 0.4
ST-T Elevation (≥ 1 mm) 0.5 0.4 0.2 0.0
2:1 AV Block 0.0 0.0 0.0 0.0
Mobitz I Second Degree AV Block 0.0 0.0 0.0 0.0
Mobitz II Second Degree AV Block 0.0 0.0 0.0 0.0
Complete Heart Block 0.0 0.0 0.0 0.0
Pause > 3.0 seconds 0.0 0.0 0.0 0.0
Any TEAE per SMQ for Myocardial Infarction 0.3 0.0 0.0 0.0
Acute Coronary Syndrome 0.2 0.0 0.0 0.0
Myocardial Infarction 0.2 0.0 0.0 0.0
Adverse Event of Angina Unstable 0.0 0.0 0.0 0.0
3.Secondary Outcome
Title Proportion of Participants With Agreement in the Assessment of Absence or Presence of Ischemia Between First and Second Stress Scans
Hide Description The number of segments with reversible defects was assessed by each of the 3 blinded independent expert readers. Based on the median count of the number of reversible defects across the 3 readers, categorized as absence (0 to 1 reversible segments) or presence (≥ 2 reversible defects) of ischemia, the proportion of participants with agreement in the presence and absence of ischemia between the first and second stress scans was calculated.
Time Frame Day 1 (stress MPI 1) and Day 2 -15 (stress MPI 2)
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Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.75
(0.68 to 0.83)
0.77
(0.67 to 0.86)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regadenoson After Peak Exercise, Regadenoson Alone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The lower confidence bound of the 1-sided alpha level of 0.025 of the difference in agreement rates must exceed -0.10 in order to demonstrate non-inferiority.
Method of Estimation Estimation Parameter Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.14 to 0.11
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.063
Estimation Comments Difference equals Regadenoson After Peak Exercise minus Regadenoson Alone
4.Secondary Outcome
Title Proportion of Participants With Agreement in the Assessment of Reversible Defects in 3 Categories of Ischemia Between First and Second Stress Scans
Hide Description The number of segments with reversible defects was assessed by each of the 3 blinded independent expert readers. Based on the median count of the number of reversible defects across the 3 readers, categorized as 0 to 1, 2 to 4, or ≥ 5 reversible segments, the proportion of participants with agreement in the three ischemia categories between the first and second stress scans was to be calculated. In the reported data, these proportions only include the 0-1 and 2-4 categories; the ≥ 5 category was not included because there were no participants in this category for the Regadenoson Alone group for the initial stress MPI.
Time Frame Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: proportion of participants
0.73
(0.69 to 0.77)
0.75
(0.71 to 0.78)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regadenoson After Peak Exercise, Regadenoson Alone
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The lower confidence bound of the 1-sided alpha level of 0.025 of the difference in agreement rates must exceed -0.133 in order to demonstrate non-inferiority. Non-inferiority could not be assessed because of insufficient data in the Regadenoson Alone group.
Method of Estimation Estimation Parameter Difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.07 to 0.04
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.027
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Proportion of Participants With Agreement in the Summed Stress Score (SSS) Between First and Second Stress Scans
Hide Description

The 17-segment model for standardized myocardial segmentation was used to analyze MPI scans. 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 Summed Stress Score (SSS) was calculated as the sum of the stress scores across the 17 segments. The mean value (rounded to the nearest integer) across the 3 readers was computed and the SSS was categorized into 4 group categorical variables based on the score: 0 to 3, 4 to 7, 8 to 11, and ≥ 12. The proportion of participants with agreement in respect to these categories between the two stress scans was calculated.

Time Frame Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Unit of Measure: proportion of participants
0.86 0.84
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Regadenoson After Peak Exercise, Regadenoson Alone
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.03 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.022
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Proportion of Participants With Agreement in the Summed Difference Score (SDS) Between First and Second Stress Scans
Hide Description

The 17-segment model for standardized myocardial segmentation was used to analyze MPI scans. 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/ uptake
  • 2: moderately reduced contrast/uptake
  • 3: severely reduced contrast/uptake
  • 4: absent contrast/uptake.

SSS was calculated as the sum of the stress scores across the 17 segments and the Summed Rest Score (SRS) was calculated as the sum of the rest scores across the 17 segments. The Summed Difference Score (SDS) is the difference in the SSS and SRS (SSS – SRS).

The mean value (rounded to the nearest integer) across the 3 readers was computed and the SDS was categorized into 3 categorical variables based on the score: 0 to 6, 7 to 13 and ≥ 14. The proportion of participants with agreement in respect to these categories between the two stress scans was calculated.

Time Frame Day 1 (rest MPI and stress MPI 1) and Day 2 - 15 (stress MPI 2)
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Full Analysis Set
Arm/Group Title REG APEX: MPI 2 SDS 0-6 REG APEX: MPI 2 7-13 REG APEX: MPI 2 SDS ≥ 14 REG Alone: MPI 2 SDS 0-6 REG Alone: MPI 2 SDS 7-13 REG Alone: MPI 2 SDS ≥ 14
Hide Arm/Group Description:
Participants in the Regadenoson After Peak Exercise (APEX) group who had an SDS from 0 to 6 on their second stress scan.
Participants in the Regadenoson After Peak Exercise (REG APEX) group who had an SDS from 7 to 13 on their second stress scan.
Participants in the Regadenoson After Peak Exercise (REG APEX) group who had an SDS ≥ 14 on their second stress scan.
Participants in the Regadenoson (REG) Alone group who had an SDS from 0 to 6 on their second stress scan.
Participants in the Regadenoson (REG) Alone group who had an SDS from 7 to 13 on their second stress scan.
Participants in the Regadenoson (REG) Alone group who had an SDS ≥ 14 on their second stress scan.
Overall Number of Participants Analyzed 538 538 538 535 535 535
Measure Type: Number
Unit of Measure: participants
MPI 1 SDS 0-6 531 4 0 527 3 0
MPI 1 SDS 7-13 0 3 0 2 3 0
MPI 1 SDS ≥ 14 0 0 0 0 0 0
7.Secondary Outcome
Title Participants With Less, the Same, or More Reversible Perfusion Defects Shown by the First Stress Scan When Compared to the Second Stress Scan
Hide Description Each reader evaluated the initial stress SPECT MPI scan compared to the participant's second stress SPECT MPI scan (blinded at time of the evaluation) for whether there was Less (-1), the Same (0) or More (1) reversible perfusion defects. The median assessment of the 3 blinded readers was used to summarize the number of participants in each category.
Time Frame Day 1 (stress MPI 1) and Day 2-15 (stress MPI 2)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Unit of Measure: participants
Less Reversible Perfusion Defects 57 49
Same Number of Reversible Perfusion Defects 441 459
More Reversible Perfusion Defects 40 27
8.Secondary Outcome
Title Overall Assessment of Image Quality
Hide Description The image quality for each scan was rated by each independent reader as 1 = Poor, 2 = Fair, 3 = Good, 4 = Excellent. Based on the median rating of overall image quality across the three readers, the number of participants with each rating is reported for each scan.
Time Frame Day 1 (rest MPI and stress MPI 1) and Day 2 - 15 (stress MPI 2)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise Regadenoson Alone
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 535
Measure Type: Number
Unit of Measure: participants
Rest MPI: Excellent 140 157
Rest MPI: Good 307 308
Rest MPI: Fair 91 70
Rest MPI: Poor 0 0
Stress MPI 1: Excellent 224 211
Stress MPI 1: Good 287 291
Stress MPI 1: Fair 27 33
Stress MPI 1: Poor 0 0
Stress MPI 2: Excellent 192 205
Stress MPI 2: Good 303 293
Stress MPI 2: Fair 43 37
Stress MPI 2: Poor 0 0
9.Secondary Outcome
Title Target to Background Radiotracer Uptake Ratios From the First and Second Stress Scans
Hide Description Image quality was assessed through radiotracer uptake in the heart (target organ) compared to liver, gut and combined liver plus gut (background interference).
Time Frame Day 1 (stress MPI 1) and Day 2 - 15 (stress MPI 2)
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Hide Analysis Population Description
Full analysis set participants who have planar images available for each scan
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 514 525 518 523
Mean (Standard Deviation)
Unit of Measure: ratio
Heart-to-Liver 1.05  (0.399) 0.94  (0.373) 0.96  (0.365) 0.95  (0.362)
Heart-to-Gut 1.12  (0.436) 0.99  (0.399) 1.05  (0.428) 0.99  (0.387)
Heart-to-(Liver/Gut) 1.02  (0.296) 0.90  (0.260) 0.94  (0.274) 0.91  (0.259)
10.Secondary Outcome
Title Percentage of Scans With Subdiaphragmatic Interference
Hide Description Each reader assessed the sub-diaphragmatic radiotracer interference with cardiac image quality using a 4-point scale of 0 = none, 1 = slight, 2 = moderate or 3 = severe for each stress SPECT MPI. The median rating across the 3 readers was used to summarize the percentage of scans with interference.
Time Frame Day 1 (stress MPI 1) and Day 2 -15 (stress MPI 2)
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Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 284 284 270 270
Measure Type: Number
Unit of Measure: percentage of stress MPI scans
None 0.4 0.0 0.0 0.0
Slight 71.8 63.7 68.1 67.4
Moderate 27.5 36.3 31.5 32.6
Severe 0.4 0.0 0.4 0.0
11.Secondary Outcome
Title Percentage of Cardiac Segments Obscured by Subdiaphragmatic Activity
Hide Description The number of cardiac segments obscured by the sub-diaphragmatic activity by group by stress SPECT MPI scan and by reader is reported.
Time Frame Day 1 (stress MPI 1) and Day - 15 (stress MPI 2)
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Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 538 538 535 535
Measure Type: Number
Unit of Measure: percentage of segments
Reader 1: Segment 1 0.0 0.0 0.0 0.0
Reader 1: Segment 2 0.0 0.0 0.0 0.0
Reader 1: Segment 3 0.0 0.0 0.0 0.0
Reader 1: Segment 4 33.6 37.2 34.2 37.4
Reader 1: Segment 5 9.7 8.4 7.9 7.7
Reader 1: Segment 6 0.0 0.0 0.0 0.0
Reader 1: Segment 7 0.0 0.0 0.0 0.0
Reader 1: Segment 8 0.0 0.0 0.0 0.0
Reader 1: Segment 9 0.0 0.0 0.0 0.0
Reader 1: Segment 10 31.6 35.5 32.3 36.3
Reader 1: Segment 11 9.5 8.2 7.5 7.5
Reader 1: Segment 12 0.0 0.0 0.0 0.0
Reader 1: Segment 13 0.0 0.0 0.0 0.0
Reader 1: Segment 14 0.0 0.0 0.0 0.0
Reader 1: Segment 15 1.7 0.9 2.4 2.1
Reader 1: Segment 16 0.0 0.0 0.2 0.2
Reader 1: Segment 17 0.0 0.0 0.0 0.0
Reader 2: Segment 1 0.0 0.0 0.0 0.0
Reader 2: Segment 2 0.0 0.0 0.2 0.0
Reader 2: Segment 3 0.0 0.0 0.2 0.6
Reader 2: Segment 4 34.4 35.1 32.5 32.5
Reader 2: Segment 5 1.1 0.4 0.7 0.7
Reader 2: Segment 6 0.0 0.0 0.0 0.0
Reader 2: Segment 7 0.0 0.0 0.0 0.0
Reader 2: Segment 8 0.0 0.2 0.0 0.0
Reader 2: Segment 9 0.0 0.0 0.4 0.4
Reader 2: Segment 10 12.6 11.9 13.8 13.1
Reader 2: Segment 11 0.0 0.2 0.6 0.2
Reader 2: Segment 12 0.0 0.0 0.0 0.0
Reader 2: Segment 13 0.0 0.0 0.0 0.0
Reader 2: Segment 14 0.0 0.0 0.0 0.0
Reader 2: Segment 15 9.1 8.7 10.5 9.5
Reader 2: Segment 16 0.0 0.2 0.0 0.0
Reader 2: Segment 17 0.4 0.0 0.0 0.0
Reader 3: Segment 1 0.0 0.2 0.0 0.0
Reader 3: Segment 2 0.0 0.0 0.0 0.0
Reader 3: Segment 3 0.0 0.0 0.0 0.0
Reader 3: Segment 4 14.1 16.7 17.9 17.2
Reader 3: Segment 5 0.6 0.4 0.7 0.2
Reader 3: Segment 6 0.0 0.0 0.0 0.0
Reader 3: Segment 7 0.0 0.0 0.0 0.0
Reader 3: Segment 8 0.0 0.0 0.0 0.0
Reader 3: Segment 9 0.0 0.0 0.0 0.0
Reader 3: Segment 10 16.0 17.8 18.5 18.9
Reader 3: Segment 11 0.7 0.2 0.6 0.2
Reader 3: Segment 12 0.0 0.0 0.0 0.0
Reader 3: Segment 13 0.2 0.0 0.0 0.0
Reader 3: Segment 14 0.0 0.0 0.0 0.0
Reader 3: Segment 15 13.9 13.8 13.1 14.6
Reader 3: Segment 16 0.4 0.7 0.4 0.2
Reader 3: Segment 17 0.9 0.9 0.7 0.6
12.Secondary Outcome
Title Number of Participants With Adverse Events Within 24 Hours After Administration of Regadenoson
Hide Description

An adverse event is considered “serious” if, in the view of either the investigator or sponsor, it results in any of the following outcomes:

  • Results in death,
  • Is life threatening,
  • Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions,
  • Results in congenital anomaly, or birth defect,
  • Requires inpatient hospitalization or leads to prolongation of hospitalization
  • Other medically important events.

Relationship to study drug was assessed by the investigator.

Time Frame Up to 24 hours after study drug administration for each stress MPI (Day 1 and Day 2-15)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set.
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description:
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
Overall Number of Participants Analyzed 575 544 567 548
Measure Type: Number
Unit of Measure: participants
Any adverse event 302 317 329 323
Drug-related adverse event 291 298 319 308
Deaths 0 0 0 0
Serious adverse events 5 2 1 1
Drug-related serious adverse events 2 0 0 0
Adverse events leading to discontinuation 13 0 5 1
Drug-related AEs leading to discontinuation 9 0 5 0
Time Frame From the time of administration of regadenoson to within 24 hours of administration of regadenoson for each stress MPI.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Hide Arm/Group Description On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, 3 minutes after exercise while in walk recovery and then a stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI. On Day 1 participants received regadenoson, 0.4 mg in a 5 mL intravenous bolus, (1 hour after exercise recovery) and then stress SPECT MPI. One to 14 days later participants received regadenoson at rest and then a stress SPECT MPI.
All-Cause Mortality
Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/575 (0.87%)   2/544 (0.37%)   1/567 (0.18%)   1/548 (0.18%) 
Cardiac disorders         
Acute coronary syndrome  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Cardiac failure congestive  1  0/575 (0.00%)  0/544 (0.00%)  1/567 (0.18%)  0/548 (0.00%) 
Myocardial infarction  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Myocardial ischaemia  1  1/575 (0.17%)  1/544 (0.18%)  0/567 (0.00%)  0/548 (0.00%) 
Eye disorders         
Vision blurred  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Gastrointestinal disorders         
Pancreatitis  1  0/575 (0.00%)  1/544 (0.18%)  0/567 (0.00%)  0/548 (0.00%) 
Investigations         
Anticoagulation drug level below therapeutic  1  0/575 (0.00%)  0/544 (0.00%)  0/567 (0.00%)  1/548 (0.18%) 
Hepatic enzyme abnormal  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Nervous system disorders         
Dizziness  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Speech disorder  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Syncope  1  1/575 (0.17%)  0/544 (0.00%)  0/567 (0.00%)  0/548 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Regadenoson After Peak Exercise: MPI 1 Regadenoson After Peak Exercise: MPI 2 Regadenoson Alone: MPI 1 Regadenoson Alone: MPI 2
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   277/575 (48.17%)   274/544 (50.37%)   307/567 (54.14%)   290/548 (52.92%) 
Gastrointestinal disorders         
Abdominal pain upper  1  31/575 (5.39%)  35/544 (6.43%)  35/567 (6.17%)  34/548 (6.20%) 
Nausea  1  43/575 (7.48%)  44/544 (8.09%)  45/567 (7.94%)  41/548 (7.48%) 
General disorders         
Chest discomfort  1  37/575 (6.43%)  33/544 (6.07%)  54/567 (9.52%)  43/548 (7.85%) 
Nervous system disorders         
Dizziness  1  106/575 (18.43%)  75/544 (13.79%)  89/567 (15.70%)  81/548 (14.78%) 
Headache  1  85/575 (14.78%)  108/544 (19.85%)  137/567 (24.16%)  118/548 (21.53%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  141/575 (24.52%)  125/544 (22.98%)  161/567 (28.40%)  152/548 (27.74%) 
Vascular disorders         
Flushing  1  47/575 (8.17%)  78/544 (14.34%)  79/567 (13.93%)  69/548 (12.59%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or 18 months after data-lock, whichever is first. Sponsor must receive a site’s manuscript at least 45 days prior to publication for review and comment. Sponsor may delay the publication for up to 60 days to seek patent protection.
Results Point of Contact
Name/Title: Senior Medical Director, Medical Affairs
Organization: Astellas Pharma Global Development, Inc. (APGD)
Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01618669     History of Changes
Other Study ID Numbers: 3606-CL-3004
First Submitted: May 29, 2012
First Posted: June 13, 2012
Results First Submitted: December 14, 2015
Results First Posted: February 8, 2016
Last Update Posted: February 8, 2016