Attenuation of the Side Effect Profile of Regadenoson: Study With Aminophylline in Patients With Severe Kidney Disease Undergoing Myocardial Perfusion Imaging

Study Overview
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Brief Summary
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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
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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).

Official Title
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Attenuation of the Side Effect Profile Of Regadenoson: A Randomized Double-Blind Placebo-Controlled Study With Aminophylline in Patients Undergoing Myocardial Perfusion Imaging and Have Severe Chronic Kidney Disease (ASSUAGE-CKD Trial)

Conditions
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Patients With Severe Chronic Kidney Disease Being Evaluated With Nuclear Stress Testing of the Heart Using the Stress Agent Regadenoson

Intervention / Treatment
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* Drug: Aminophylline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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®).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aminophylline<br>75 mg of intravenous aminophylline. | Drug: Aminophylline<br>* 75 mg of intravenous aminophylline<br>|
| Placebo Comparator: Placebo<br>Matching 0.9 Normal Saline (sterile salt water)administered intravenously. | Drug: Placebo<br>* Matching 0.9 Normal Saline (sterile salt water)administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Within 2 hours from the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Within 2 hours from the intervention. | 
| 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 | Within 2 hours from the intervention. | 
| 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. | Within 24 hours from the intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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 ®)