Cardiorenal Syndrome
Conditions
Brief summary
The objective of this study is to determine the safety and effectiveness of intrarenal administration of brain natriuretic peptide (BNP) in improving renal function as measured by glomerular filtration rate (GFR) and sodium excretion in patients hospitalized with acute congestive heart failure (CHF) and deterioration of kidney function (cardiorenal syndrome).
Interventions
DRUGNesiritide
Nesiritide 0.005 ug/kg/min IV for 6 hours, then to 0.01 ug/kg/min for 6 hours then to 0.02ug/kg/min for 6 hours then to 0.03 ug/kg/min for the last 6 hours.
Sponsors
FlowMedica, Inc.
Horng Chen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older * Clinical diagnosis of class III-IV CHF requiring hospitalization * Current acute CHF decompensation * Systolic BP \> 90 mmHg * Stable cardiac rhythm * Estimated creatinine clearance by the Cockcroft-Gault equation of less than or equal to 60 mL/min. * Worsening renal function after greater than or equal to 24 hours of standard therapy as defined by a plasma creatinine concentration greater than their admission of 0.3 mg/dL and a 10% increase from hospital admission creatinine OR creatinine which remains at 0.3 mg/dL and 10% increase from baseline draw done within 4 weeks of hospitalization * Ability to provide informed consent
Exclusion criteria
* Patients needing emergency coronary revascularization or those who may have rapidly changing cardiac function (i.e., patients with acute myocardial infarction or shock) * Peritoneal or hemodialysis within 90 days or anticipation that dialysis or ultrafiltration of any form will be required during the study period * Systolic blood pressure \< 90 mmHg or cardiogenic shock * Requirement of pressors for maintenance of blood pressure * Intra-aortic blood pump use * History of significant uncorrected renal artery stenosis as defined by \>50% stenosis * Severe aortic or mitral stenosis or significant LV outflow tract obstruction * Pregnant or nursing women * Prisoners * Contraindication to nesiritide * Contraindication to heparin * Cause of acute renal dysfunction can be reasonably ascribed to factors other than heart failure or its treatment * Inability to have NSAID dose held for up to 30 hours, if being treated with these medications * Ongoing treatment with calcineurin inhibitors (cyclosporine or tacrolimus) * Administration of radiocontrast medium within 7 days of enrollment or anticipated use of such agents during the study (other than the minimal contrast required to place the renal infusion catheter) * Known bleeding diathesis * Known condition that would increase the likelihood of vascular perforation or trauma, dissection such as Marfan's syndrome, cystic medial necrosis, abdominal or thoracoabdominal aortic dissection, mycotic aneurysm, abdominal aneurysm, thoracoabdominal aneurysm, renal artery aneurysm, thoracic aneurysm involving the visceral region of the aorta, and severe calcification in the area of the renal arteries * Solitary kidney or solitary functioning kidney * Iodine allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glomerular Filtration Rate (GFR) at 24 Hours | baseline, 24 hours after start of infusion | Kidney function was to be measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m\^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m\^2 of body surface area is considered to be impaired kidney function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Sodium Excretion at 24 Hours | baseline, 24 hours after start of infusion | The fractional excretion of sodium (FENa) measures the percent of filtered sodium that is excreted in the urine. This calculation is widely used to help differentiate prerenal disease (decreased renal perfusion) from acute tubular necrosis (ATN) as the cause of acute kidney injury (AKI, formerly called acute renal failure). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the Mayo Clinic in Rochester, MN.
Participants by arm
| Arm | Count |
|---|---|
| Nesiritide Subjects received an intrarenal infusion of nesiritide at 0.005 microgram/kg/min for 6 hours, 0.01 microgram/kg/min for 6 hours, 0.02 microgram/kg/min for 6 hours, and 0.03 microgram/kg/min for 6 hours. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Nesiritide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 4 |
| other Total, other adverse events | 1 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
Change in Glomerular Filtration Rate (GFR) at 24 Hours
Kidney function was to be measured by GFR determined by iothalamate clearance. GFR describes the flow rate of filtered fluid through the kidney measured in milliliters per minute per 1.73 m\^2 of body surface area. A lower GFR means the kidney is not filtering normally. An estimated GFR of less than 60 mg/min/1.73 m\^2 of body surface area is considered to be impaired kidney function.
Time frame: baseline, 24 hours after start of infusion
Population: The data from the 3 subjects were incomplete and could not be analyzed.
Secondary
Change in Urinary Sodium Excretion at 24 Hours
The fractional excretion of sodium (FENa) measures the percent of filtered sodium that is excreted in the urine. This calculation is widely used to help differentiate prerenal disease (decreased renal perfusion) from acute tubular necrosis (ATN) as the cause of acute kidney injury (AKI, formerly called acute renal failure).
Time frame: baseline, 24 hours after start of infusion
Population: The data from the 3 subjects were incomplete and could not be analyzed.