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

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)

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.

Study Overview

• Status: Completed
• Conditions: Patients With Severe Chronic Kidney Disease Being Evaluated With Nuclear Stress Testing of the Heart Using the Stress Agent Regadenoson
• Intervention / Treatment: Drug: Aminophylline; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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®).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Collaborators: John H. Stroger Hospital
• Investigators: Principal Investigator: Rami Doukky, MD, Rush University Medical Center

Publications and helpful links

General Publications

• Doukky R, Rangel MO, Dick R, Wassouf M, Alqaid A, Margeta B. 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--the ASSUAGE-CKD trial. Int J Cardiovasc Imaging. 2013 Jun;29(5):1029-37. doi: 10.1007/s10554-012-0166-6. Epub 2012 Dec 11.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: April 11, 2011
• First Submitted That Met QC Criteria: April 14, 2011
• First Posted (Estimate): April 15, 2011

Study Record Updates

• Last Update Posted (Actual): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 3, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: chronic kidney disease; Myocardial Perfusion Imaging; renal failure; SPECT; regadenoson; lexiscan; aminophylline; 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 ®)
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Purinergic Antagonists; Purinergic Agents; Protective Agents; Cardiotonic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Aminophylline
• Other Study ID Numbers: ASSUAGE-CKD; 110129 (Other Identifier: FDA - IND)