Partial Nephrectomy
Conditions
Keywords
nephrectomy, fenoldopam, atrophic minimally functioning kidney
Brief summary
This trial will study the effects of fenoldopam on renal function in patients who have a single kidney undergoing surgery to remove part of that kidney secondary to renal cell carcinoma. The investigators will monitor and evaluate throughout the perioperative course the kidney function. Normally kidney function is predicted to show a worsening followed by an improvement after surgery. The investigators want to specifically identify if the use of fenoldopam lessens the injury to the kidney with this surgery.
Detailed description
Prospective, randomized, blinded study-dividing patients into one of two groups: fenoldopam or placebo. The infusion will commence after placing the patient in a lateral/flex position during the operation. The infusion will continue for a total of 24 hours.Study time period will be approximately six weeks from the date of surgery. Specifically, the following pre- and post operative laboratory results will be recorded if available: . Basic metabolic panel - pre-op, post op days 1, 2, 3, 4, and 6 weeks * Serum osmolality, urine osmolality, urine sodium - pre-op, post op days 1, 3 * Glomerular filtration rate - pre-op, post op days 1, 3, and 6 weeks
Interventions
DRUGFenoldopam
Fenoldopam (0.1 \ g/kg/min)started during surgery and lasting for a total of 24 hours
DRUGPlacebo
Placebo infusion(0.9% Nacl) beginning during surgery and lasting for up 24 hours post surgery
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients who have a solitary kidney and present for a partial nephrectomy * Patients who have one atrophic minimally functioning kidney and present for partial nephrectomy on the other kidney
Exclusion criteria
* History of current renal disease beyond the diagnosis of renal malignancy * Insulin dependent diabetes mellitus, myocardial infarction without subsequent coronary artery bypass or angioplasty * History of congestive heart failure, renovascular occlusion greater than 45 minutes or less than 15 minutes, greater than one half of the solitary kidney resected * A major perioperative complication that would potentially affect postoperative renal function (myocardial infarction, congestive heart failure, pulmonary embolus, massive hemorrhage and hypotension, ureteral obstruction or vascular thrombosis), and evidence of nephrotoxicity due to antibiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glomerular Filtration Rate (GFR) Percentage of Change From Baseline | percentage of change from baseline to post-operatively day 3 | Our intended primary analysis was to assess the effect of fenoldopam vs placebo on the GFR at post-operative day (POD) 3 with an analysis of covariance adjusting for the baseline GFR. However, because the intervention-by-baseline GFR interaction using GFR at POD 3 as the outcome was significant (P ¼ .006), the analysis of covariance was not valid. We, therefore, used the GFR percentage of change from baseline to POD 3 as the primary outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Creatinine (mg/dL) | immediately postoperative, postoperative day 1, postoperative day 2, postoperative day 3, postoperative day 4 | assessed the effect of fenoldopam on creatinine over time (immediately postoperatively and on postoperative day 1, 2, 3, 4) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (0.9% Nacl)infusion beginning during surgery and lasting for up to 24 hours
Placebo: Placebo infusion(0.9% Nacl) beginning during surgery and lasting for up 24 hours post surgery | 34 |
| Fenoldopam Fenoldopam (0.1 \
g/kg/min)infusion will commence after placing the patient in a lateral/flex position during the operation. The infusion will continue for a total of 24 hours.
Fenoldopam: Fenoldopam (0.1 \
g/kg/min)started during surgery and lasting for a total of 24 hours | 43 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Met intraoperative exclusion criterion | 8 | 5 |
Baseline characteristics
| Characteristic | Placebo | Fenoldopam | Total |
|---|---|---|---|
| Age, Continuous | 59 years STANDARD_DEVIATION 9 | 59 years STANDARD_DEVIATION 10 | 59 years STANDARD_DEVIATION 10 |
| creatinine | 1.2 mg/dL | 1.2 mg/dL | 1.2 mg/dL |
| GFR | 59 mL/min STANDARD_DEVIATION 19 | 59 mL/min STANDARD_DEVIATION 19 | 59 mL/min STANDARD_DEVIATION 19 |
| Race/Ethnicity, Customized Others | 3 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized White | 31 participants | 42 participants | 73 participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 15 Participants |
| Sex: Female, Male Male | 29 Participants | 33 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 42 |
| serious Total, serious adverse events | 0 / 34 | 0 / 42 |
Outcome results
Primary
Glomerular Filtration Rate (GFR) Percentage of Change From Baseline
Our intended primary analysis was to assess the effect of fenoldopam vs placebo on the GFR at post-operative day (POD) 3 with an analysis of covariance adjusting for the baseline GFR. However, because the intervention-by-baseline GFR interaction using GFR at POD 3 as the outcome was significant (P ¼ .006), the analysis of covariance was not valid. We, therefore, used the GFR percentage of change from baseline to POD 3 as the primary outcome.
Time frame: percentage of change from baseline to post-operatively day 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Glomerular Filtration Rate (GFR) Percentage of Change From Baseline | -39 percentage change | Standard Deviation 28 |
| Fenoldopam | Glomerular Filtration Rate (GFR) Percentage of Change From Baseline | -28 percentage change | Standard Deviation 38 |
p-value: 0.1595% CI: [-31, 9]Wilcoxon (Mann-Whitney)
Secondary
Postoperative Creatinine (mg/dL)
assessed the effect of fenoldopam on creatinine over time (immediately postoperatively and on postoperative day 1, 2, 3, 4)
Time frame: immediately postoperative, postoperative day 1, postoperative day 2, postoperative day 3, postoperative day 4
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Postoperative Creatinine (mg/dL) | postoperative day 1 | 2.14 mg/dL | Standard Error 0.11 |
| Placebo | Postoperative Creatinine (mg/dL) | postoperative day 3 | 2.65 mg/dL | Standard Error 0.25 |
| Placebo | Postoperative Creatinine (mg/dL) | postoperative day 2 | 2.66 mg/dL | Standard Error 0.23 |
| Placebo | Postoperative Creatinine (mg/dL) | postoperative day 4 | 2.76 mg/dL | Standard Error 0.3 |
| Placebo | Postoperative Creatinine (mg/dL) | immediately postoperative | 1.44 mg/dL | Standard Error 0.07 |
| Fenoldopam | Postoperative Creatinine (mg/dL) | postoperative day 4 | 2.61 mg/dL | Standard Error 0.33 |
| Fenoldopam | Postoperative Creatinine (mg/dL) | immediately postoperative | 1.37 mg/dL | Standard Error 0.06 |
| Fenoldopam | Postoperative Creatinine (mg/dL) | postoperative day 1 | 2.04 mg/dL | Standard Error 0.12 |
| Fenoldopam | Postoperative Creatinine (mg/dL) | postoperative day 2 | 2.38 mg/dL | Standard Error 0.19 |
| Fenoldopam | Postoperative Creatinine (mg/dL) | postoperative day 3 | 2.46 mg/dL | Standard Error 0.25 |
Comparison: We assessed the effect of fenoldopam on creatinine over time (immediately postoperatively and on PODs 1-4). A linear mixed effects model was used to assess the main effect of fenoldopam on the postoperative log-transformed (base 2) serum creatinine, adjusting for baseline serum creatinine.p-value: 0.7895% CI: [0.79, 1.19]Mixed Models Analysis