Patients With Severe Chronic Kidney Disease Being Evaluated With Nuclear Stress Testing of the Heart Using the Stress Agent Regadenoson
Conditions
Keywords
regadenoson, chronic kidney disease, renal failure, lexiscan, aminophylline, SPECT, Myocardial Perfusion Imaging, pharmacologic stress test, Patients with stage IV or V chronic kidney disease being assessed with nuclear stress testing of the heart using the stress agent regadenoson (Lexiscan ®)
Brief summary
The routine administration of 75 mg of intravenous aminophylline in patients with severe chronic kidney disease undergoing a nuclear stress test with regadenoson (Lexiscan®) can reduce or eliminate the incidence of diarrhea and other side effects related to regadenoson.
Detailed description
Approximately 300 patients with severe chronic kidney disease who are referred for a nuclear stress testing of the heart with regadenoson (Lexiscan®) will be recruited to participate in the study. Following regadenoson (administered as part of a stress routine test protocol) participants will receive either aminophylline (75 mg - intravenously) or a matching inactive placebo (sterile salt water) injection. Participants will be surveyed for gastrointestinal symptoms and other side effects related to regadenoson. The frequency and severity of such side effects will be compared between the two study groups (aminophylline vs. placebo).
Interventions
DRUGAminophylline
75 mg of intravenous aminophylline
DRUGPlacebo
Matching 0.9 Normal Saline (sterile salt water)administered intravenously.
Sponsors
Cook County Health
Rush University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients referred to undergo a clinically-indicated regadenoson-stress myocardial perfusion imaging at Rush University Medical Center * Stage IV or V chronic kidney disease (GFR \< 30, hemodialysis, and/or peritoneal dialysis).
Exclusion criteria
* Patient refusal to participate * Known allergic reaction to aminophylline. * Pre-existing headache or acute/subacute GI illness with symptoms of diarrhea, abdominal discomfort, nausea or vomiting. * Any contraindication to aminophylline: hypotension, unstable cardiac arrhythmias and acute coronary symptoms. * Uncontrolled seizure disorder defined as more than 2 seizure episodes in the past 12 months or any seizure in the past week. * Pregnant or breast-feeding women. * Patients receiving anti-platelet agent dipyridamole (Persantine® or Aggrenox®).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Diarrhea (as Reported by the Patient) | Within 2 hours from the intervention | Number of patients who report any incident of diarrhea. Patients will be surveyed for incidents of diarrhea following to the completion of the cardiac stress testing procedure and prior to discharge from the laboratory (typically within 2 hours from stress completion). The primary endpoint encompasses the number of patients with reported symptoms of diarrhea, not the number of bowel movements. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Any (One or More) Regadenoson-related Adverse-effect | Within 2 hours from the intervention. | Regadenoson-related adverse-effects include: flushing, feeling hot, chest pain, chest discomfort, angina, headache, dizziness, abdominal cramps or discomfort, diarrhea, nausea. When multiple adverse effects are reported, only one event is counted. |
| Global Symptom Score (GSS) of Regadenoson Related Adverse-effects | Within 2 hours from the intervention. | GSS is the sum of severity-weighted (0 = none, 1 = mild, 2 = moderate, 3 = severe) regadenosnon-related adverse-effects of flushing, feeling hot, chest pain, chest discomfort, angina, headache, dizziness, abdominal cramps or discomfort, diarrhea, nausea. GSS is calculated by weighting each side effect from 0 - 3 (as above) then add the severity weighted scores of all adverse effects (total of 10 as above). The number of adverse effects contributing to the score is 10, each has a potential severity weight of 0 (absent) to 3 (severe). Thus: Minimum possible Global Symptom Score (GSS) = 0 Maximum possible Global Symptom Score (GSS) = 30 |
| Patients With Recorded Aminophylline Related Major Adverse Events | Within 24 hours from the intervention. | Aminophylline related adverse effects include: systemic hypotension (systolic blood pressure \< 90 mmHg), any thachyarrhythmia (ventricular or supraventricular) and seizure. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited in the period from June 14, 2011 to May 14, 2012 in the stress testing laboratories of Rush University medical center and John H. Stroger, Jr. Hospital of Cook County (Chicago, IL.
Pre-assignment details
427 patients were recruited. 122 patients were excluded: 50 refused; 35 met an exclusion criteria; 1 was previously enrolled in the trial; 26 had a contraindication to aminophylline. 5 consenting subjects were excluded: 3 had their regadenoson-stress clinically cancelled; 2 treatment assignment could not be verified (labeling error).
Participants by arm
| Arm | Count |
|---|---|
| Aminophylline 75 mg of intravenous aminophylline. | 150 |
| Placebo Matching 0.9 Normal Saline (sterile salt water)administered intravenously. | 150 |
| Total | 300 |
Baseline characteristics
| Characteristic | Total | Aminophylline | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 64 Participants | 25 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 236 Participants | 125 Participants | 111 Participants |
| Age, Continuous | 55 years STANDARD_DEVIATION 13 | 54 years STANDARD_DEVIATION 13 | 56 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 300 participants | 150 participants | 150 participants |
| Sex: Female, Male Female | 107 Participants | 53 Participants | 54 Participants |
| Sex: Female, Male Male | 193 Participants | 97 Participants | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 150 | 0 / 150 |
| other Total, other adverse events | 0 / 150 | 0 / 150 |
| serious Total, serious adverse events | 0 / 150 | 0 / 150 |
Outcome results
Primary
Diarrhea (as Reported by the Patient)
Number of patients who report any incident of diarrhea. Patients will be surveyed for incidents of diarrhea following to the completion of the cardiac stress testing procedure and prior to discharge from the laboratory (typically within 2 hours from stress completion). The primary endpoint encompasses the number of patients with reported symptoms of diarrhea, not the number of bowel movements.
Time frame: Within 2 hours from the intervention
Population: All patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aminophylline | Diarrhea (as Reported by the Patient) | 9 participants |
| Placebo | Diarrhea (as Reported by the Patient) | 26 participants |
Comparison: We calculated that a minimum of 248 subjects are needed to attain 80% power to detect 70% reduction in the incidence of the primary endpoint (diarrhea), assuming an event rate of 15% in the control group (2-tailed α = 0.05). We targeted enrolling 300 patients to allow some room for error in our assumptions.~null hypothesis: incidence of diarrhea is no different between the aminophylline arm and the placebo arm.p-value: 0.002Chi-squared
Secondary
Global Symptom Score (GSS) of Regadenoson Related Adverse-effects
GSS is the sum of severity-weighted (0 = none, 1 = mild, 2 = moderate, 3 = severe) regadenosnon-related adverse-effects of flushing, feeling hot, chest pain, chest discomfort, angina, headache, dizziness, abdominal cramps or discomfort, diarrhea, nausea. GSS is calculated by weighting each side effect from 0 - 3 (as above) then add the severity weighted scores of all adverse effects (total of 10 as above). The number of adverse effects contributing to the score is 10, each has a potential severity weight of 0 (absent) to 3 (severe). Thus: Minimum possible Global Symptom Score (GSS) = 0 Maximum possible Global Symptom Score (GSS) = 30
Time frame: Within 2 hours from the intervention.
Population: All patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Aminophylline | Global Symptom Score (GSS) of Regadenoson Related Adverse-effects | 1.7 Global Symptom Score | Standard Deviation 0.8 |
| Placebo | Global Symptom Score (GSS) of Regadenoson Related Adverse-effects | 2.1 Global Symptom Score | Standard Deviation 1.6 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Patients With Any (One or More) Regadenoson-related Adverse-effect
Regadenoson-related adverse-effects include: flushing, feeling hot, chest pain, chest discomfort, angina, headache, dizziness, abdominal cramps or discomfort, diarrhea, nausea. When multiple adverse effects are reported, only one event is counted.
Time frame: Within 2 hours from the intervention.
Population: All patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aminophylline | Number of Patients With Any (One or More) Regadenoson-related Adverse-effect | 47 Participants |
| Placebo | Number of Patients With Any (One or More) Regadenoson-related Adverse-effect | 96 Participants |
p-value: <0.001Chi-squared
Secondary
Patients With Recorded Aminophylline Related Major Adverse Events
Aminophylline related adverse effects include: systemic hypotension (systolic blood pressure \< 90 mmHg), any thachyarrhythmia (ventricular or supraventricular) and seizure.
Time frame: Within 24 hours from the intervention.
Population: All patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aminophylline | Patients With Recorded Aminophylline Related Major Adverse Events | 0 participant |
| Placebo | Patients With Recorded Aminophylline Related Major Adverse Events | 0 participant |
p-value: 1Chi-squared