Chronic Renal Insufficiency, Congestive Heart Failure, Diabete Mellitus
Conditions
Keywords
CATH Catheterization, CI-AKI Contrast-induced acute kidney injury, DM Diabetes mellitus, eGFR Estimated glomerular filtration rate, MDRD Modification of Diet in Renal Disease, NYHA New York Heart Association, PCI Percutaneous coronary intervention, SCr Serum creatinine
Brief summary
To evaluate cardio-renal and overall safety profile of GE 145 320 mg I/ml Injection when compared to iopamidol 370 mg I/mL. The study will focus on elderly subjects with either chronic renal insufficiency, or diabetes mellitus (DM) requiring drug therapy, or congestive heart failure (CHF) NYHA Class III or greater, who are referred for a coronary catheterization procedure with or without PCI.
Interventions
DRUGGE-145
GE-145-320 mg I/mL as a single iv. administration. Comparator agent Isovue (iopamidol) 370 mg I/mL as a single iv. administration.
Sponsors
i3 Statprobe
Medpace, Inc.
Biomedical Systems
Rules-Based Medicine, Inc.
GE Healthcare
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females 65 years of age with cardiovascular disease who are referred for a coronary catheterization procedure with or without PCI. * The subject has at least one of the following comorbidities: * 1\) Chronic renal insufficiency, (eGFR \<60 but 15 mL/min/1.73 m2 according to the MDRD equation) as measured within 2 weeks or at the screening visit; * 2\) DM diagnosed greater than 6 months prior to study entry and which requires either insulin or anti-hyperglycemic drug therapy; * 3\) CHF (NYHA) class III or greater measured within 2 weeks of enrollment or at the screening visit.
Exclusion criteria
* The subject has known allergies to either iodine or any ICM. * The subject has severe renal insufficiency (eGFR \<15 mL/min/1.73 m2 according to the MDRD equation) or is on dialysis. * The subject has acute coronary syndrome requiring emergency coronary angiography and/or intervention. * The subject is not willing or unable to discontinue metformin (e.g., Glucophage) at the time of the study procedure.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | After the imaging date for either Ioforminol or Iopamidol. | Overall image quality (excellent, adequate or poor) and diagnostic usefulness (diagnostic or non-diagnostic) were assessed using qualitative scales. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Time zero equals the date of contrast imaging and for up to 7 days for safety monitoring post contrast administration. | To determine incidence rates of the overall AEs, organ-specific AEs (i.e., delayed skin reactions, general subject comfort, and allergic/immunologic reactions, etc.) and SAEs following administration of GE-145 or iopamidol. To determine incidence rates and onset time of biomarker-based and SCr-based CI-AKI following administration of GE-145 or iopamidol. Summary of Treatment-Emergent Adverse Events (TEAE) in greater than of equal to 2% of Subjects. |
| Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | 2, 6 and 24 hours post Ioforminol and Iopamidol adminstration | Analyzing the number of subjects with renal biomarker-based contrast-induced acute kidney injury (CI-AKI). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ioforminol 320mg I/ml Injection Ioforminol 320 mg I/mL as a single iv. administration. | 137 |
| Iopamidol 370mg I/ml Injection Iopamidol 370 mg I/mL as a single iv. administration. | 141 |
| Total | 278 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Physician Decision | 2 | 1 |
| Overall Study | Various reasons | 8 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | Ioforminol 320mg I/ml Injection | Iopamidol 370mg I/ml Injection | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 109 Participants | 111 Participants | 220 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 30 Participants | 58 Participants |
| Region of Enrollment Canada | 9 participants | 7 participants | 16 participants |
| Region of Enrollment United States | 128 participants | 134 participants | 262 participants |
| Sex: Female, Male Female | 48 Participants | 53 Participants | 101 Participants |
| Sex: Female, Male Male | 89 Participants | 88 Participants | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 137 | 9 / 141 |
| serious Total, serious adverse events | 13 / 137 | 10 / 141 |
Outcome results
Primary
Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader.
Overall image quality (excellent, adequate or poor) and diagnostic usefulness (diagnostic or non-diagnostic) were assessed using qualitative scales.
Time frame: After the imaging date for either Ioforminol or Iopamidol.
Population: The measured values are looking at 1) Overall Image Quality and, 2) Diagnostic Usefulness.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ioforminol 320mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overall Image Quality-Adequate | 57 Number of subjects |
| Ioforminol 320mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Diagnostic Usefulness-Diagnostic | 123 Number of subjects |
| Ioforminol 320mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overal Image Quality-Poor | 15 Number of subjects |
| Ioforminol 320mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Diagnostic Usefulness-Non-Diagnostic | 14 Number of subjects |
| Ioforminol 320mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overall Image Quality-Excellent | 65 Number of subjects |
| Iopamidol 370mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Diagnostic Usefulness-Non-Diagnostic | 7 Number of subjects |
| Iopamidol 370mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overall Image Quality-Excellent | 71 Number of subjects |
| Iopamidol 370mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overall Image Quality-Adequate | 59 Number of subjects |
| Iopamidol 370mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Overal Image Quality-Poor | 11 Number of subjects |
| Iopamidol 370mg I/ml Injection | Comparison of Overall Image Quality Between Ioforminol and Iopamidol-enhanced Images as Determined by an Independent Reader. | Diagnostic Usefulness-Diagnostic | 134 Number of subjects |
Secondary
Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections
Analyzing the number of subjects with renal biomarker-based contrast-induced acute kidney injury (CI-AKI).
Time frame: 2, 6 and 24 hours post Ioforminol and Iopamidol adminstration
Population: Summary of subjects with renal biomarker-based CI-AKI by time point (Per Protocol Population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ioforminol 320mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 2 hours | 24 Subjects |
| Ioforminol 320mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 6 hours | 48 Subjects |
| Ioforminol 320mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 24 hourss | 61 Subjects |
| Iopamidol 370mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 2 hours | 21 Subjects |
| Iopamidol 370mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 6 hours | 33 Subjects |
| Iopamidol 370mg I/ml Injection | Assessing the Incidence of Renal Biomarker-based Contrast-induced Acute Kidney Injury (CI-AKI) in Subjects Post Administration of Ioforminol or Iopamidol Injections | Time- Post Contrast, 24 hourss | 49 Subjects |
Secondary
To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration
To determine incidence rates of the overall AEs, organ-specific AEs (i.e., delayed skin reactions, general subject comfort, and allergic/immunologic reactions, etc.) and SAEs following administration of GE-145 or iopamidol. To determine incidence rates and onset time of biomarker-based and SCr-based CI-AKI following administration of GE-145 or iopamidol. Summary of Treatment-Emergent Adverse Events (TEAE) in greater than of equal to 2% of Subjects.
Time frame: Time zero equals the date of contrast imaging and for up to 7 days for safety monitoring post contrast administration.
Population: Summary of Treatment-Emergent Adverse Events (TEAE) in greater than of equal to 2% of Subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Angina Pectoris | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Urinary Tract Infection | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Coronary Artery Disease | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Diarrhea | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Nausea | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Hematoma | 9 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Hemorrhage | 4 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Pain | 4 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Chest Pain | 3 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Blood Creatinine Increased | 2 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Pain In Extremity | 2 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Dizziness | 0 Number of events |
| Ioforminol 320mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Headache | 11 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Dizziness | 3 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Pain | 3 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Angina Pectoris | 2 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Pain In Extremity | 5 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Coronary Artery Disease | 3 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Chest Pain | 2 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Diarrhea | 1 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Urinary Tract Infection | 4 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Nausea | 3 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Headache | 1 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Hematoma | 8 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Blood Creatinine Increased | 4 Number of events |
| Iopamidol 370mg I/ml Injection | To Determine Incidence Rates of the Overall AEs, Organ-specific AEs (i.e., Delayed Skin Reactions, General Subject Comfort, and Allergic/Immunologic Reactions, Etc.) and SAEs Following Administration | Catheter-Site Hemorrhage | 6 Number of events |