Renal Cancer
Conditions
Keywords
Kidney, MANNITOL, PLACEBO, Partial Nephrectomy, 12-079
Brief summary
The purpose of this study is to determine if a medication called mannitol, can help the kidney maintain its function after kidney surgery. Mannitol is used to cause an increase in urine production (it is a diuretic). For many years, mannitol has been given to patients in the hope it would improve the kidney's circulation, and in doing so reduce the impact of the surgery on the kidney. Mannitol is given during the surgery before the blood supply to the kidney is stopped. The blood supply to the kidney is stopped in order to minimize any blood loss during the removal of the tumor, and also to assist the surgeons view of the kidney anatomy. Once the tumor is removed the blood supply to the kidney is resumed. Sometimes a side effect of this temporary reduction in blood supply to the kidney is the loss of some kidney function. This may happen either in the short term (right away) or long term (months or years later). In studies done on animals, mannitol was able to lessen this damage to kidney function. However, no human study has ever confirmed that mannitol has the same helpful effect in humans. There is some suggestion that it may have no effect. Because sufficient research has yet to be done on humans, many surgeons do not give mannitol. A recent study, conducted at Memorial Sloan Kettering which looked back at patients who had undergone partial nephrectomies, an operation where only the portion of the kidney that contains the tumor is removed and enables the normal, unaffected portion of the kidney to be preserved. The results of this study demonstrated no significant difference in kidney function when the investigators compared patients who were given mannitol to those who were not. The investigators hope that this study will help clarify the effectiveness or not of mannitol on kidney function. During the surgery to remove the kidney tumor, patients will receive either mannitol or a placebo. A placebo, is a harmless medication that has no effects. The impact of mannitol compared to the placebo will be assessed by routine blood tests and imaging (kidney scan) 6 months after your surgery.
Interventions
DRUGmannitol
After induction of general anesthesia Normosol or Lactated Ringers , at a target infusion rate of 10cc/kg (+/- 1cc/kg), will be administered over the first hour of surgery. After the first hour of surgery IV fluid will be administered at 6cc/kg (+/- 1cc/kg) intended to maintain a minimum systolic blood pressure of 90-100mmHg and a minimum urine output of 0.5cc/kg/hour. The treatment arm will receive a standard dose of 12.5 grams of mannitol (200 cc of a 6.25% mannitol solution) intravenously completely infused through an existing intravenous access catheter within 30 minutes prior to renal artery clamping.
OTHERplacebo
After induction of general anesthesia Normosol or Lactated Ringers at a target infusion rate of 10cc/kg (+/- 1cc/kg), will be administered over the first hour of surgery. After the first hour of surgery IV fluid will be administered at 6cc/kg (+/- 1cc/kg) intended to maintain a minimum systolic blood pressure of 90-100mmHg and a minimum urine output of 0.5cc/kg/hour. The placebo arm will receive 200cc of normal saline completely infused within 30 minutes prior to renal artery clamping.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \> or = to 18 years * Scheduled for partial nephrectomy at MSKCC (open or minimally invasive technique) during which renal ischemia is anticipated * Preoperative eGFR \> 45 cc/min/1.73m2 as measured by the CKD-EPI study equation
Exclusion criteria
* Allergy to mannitol * Severe renal impairment (stage 3B) defined as eGFR \< 45 cc/min/1.73m2 as measured by the CKD-EPI calculation. * Combined major surgical cases that include a partial nephrectomy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months | 6 months | The difference will be assessed with an ANCOVA model with eGFR 6 months after surgery (+/- 2 months) as the outcome and treatment group, surgical technique, and preoperative eGFR as covariates. We will report a two-tailed p-value and a 95% confidence interval for the difference between groups. If a patient does not have an eGFR measurement between 5-7 months after surgery and has both a measurement between 3-5 months and 7-12 months after surgery, then the 6 month eGFR measurement will be linearly interpolated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks | 6 weeks | between treatment groups at 6 weeks (+/- 4 weeks) after surgery with postoperative eGFR as the outcome, and treatment group, surgical technique, and preoperative eGFR as covariates. We will also use the ANCOVA on the absolute level of eGFR because this has the greatest statistical power. However, the estimate produced by ANCOVA - a mean difference in eGFR levels - is of incomplete clinical interpretability. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mannitol Arm This study is a prospective randomized double blind placebo controlled trial comparing renal function outcomes in patients undergoing partial nephrectomy for renal tumors. Patients will be randomized in 1:1 fashion to receive mannitol or saline provided intravenously within 30 minutes prior to renal vascular clamping for performing partial nephrectomy.
mannitol: After induction of general anesthesia Normosol or Lactated Ringers , at a target infusion rate of 10cc/kg (+/- 1cc/kg), will be administered over the first hour of surgery. After the first hour of surgery IV fluid will be administered at 6cc/kg (+/- 1cc/kg) intended to maintain a minimum systolic blood pressure of 90-100mmHg and a minimum urine output of 0.5cc/kg/hour. The treatment arm will receive a standard dose of 12.5 grams of mannitol (200 cc of a 6.25% mannitol solution) intravenously completely infused through an existing intravenous access catheter within 30 minutes prior to renal artery clamping. | 101 |
| Placebo Arm This study is a prospective randomized double blind placebo controlled trial comparing renal function outcomes in patients undergoing partial nephrectomy for renal tumors. Patients will be randomized in 1:1 fashion to receive mannitol or saline provided intravenously within 30 minutes prior to renal vascular clamping for performing partial nephrectomy.
placebo: After induction of general anesthesia Normosol or Lactated Ringers at a target infusion rate of 10cc/kg (+/- 1cc/kg), will be administered over the first hour of surgery. After the first hour of surgery IV fluid will be administered at 6cc/kg (+/- 1cc/kg) intended to maintain a minimum systolic blood pressure of 90-100mmHg and a minimum urine output of 0.5cc/kg/hour. The placebo arm will receive 200cc of normal saline completely infused within 30 minutes prior to renal artery clamping. | 98 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Surgery canceled | 0 | 2 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Mannitol Arm | Total | Placebo Arm |
|---|---|---|---|
| Age, Continuous | 60 years | 58 years | 56 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 15 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 13 Participants | 3 Participants |
| Race (NIH/OMB) White | 81 Participants | 161 Participants | 80 Participants |
| Region of Enrollment United States | 101 Participants | 199 Participants | 98 Participants |
| Sex: Female, Male Female | 36 Participants | 73 Participants | 37 Participants |
| Sex: Female, Male Male | 65 Participants | 126 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 101 | 2 / 98 |
| other Total, other adverse events | 2 / 101 | 7 / 98 |
| serious Total, serious adverse events | 19 / 101 | 11 / 98 |
Outcome results
Primary
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months
The difference will be assessed with an ANCOVA model with eGFR 6 months after surgery (+/- 2 months) as the outcome and treatment group, surgical technique, and preoperative eGFR as covariates. We will report a two-tailed p-value and a 95% confidence interval for the difference between groups. If a patient does not have an eGFR measurement between 5-7 months after surgery and has both a measurement between 3-5 months and 7-12 months after surgery, then the 6 month eGFR measurement will be linearly interpolated.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mannitol Arm | Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months | -8.5 % change from preoperative eGFR | Standard Deviation 14 |
| Placebo Arm | Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months | -8.4 % change from preoperative eGFR | Standard Deviation 12 |
Secondary
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks
between treatment groups at 6 weeks (+/- 4 weeks) after surgery with postoperative eGFR as the outcome, and treatment group, surgical technique, and preoperative eGFR as covariates. We will also use the ANCOVA on the absolute level of eGFR because this has the greatest statistical power. However, the estimate produced by ANCOVA - a mean difference in eGFR levels - is of incomplete clinical interpretability.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mannitol Arm | Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks | -6.2 % change from preoperative eGFR | Standard Deviation 13 |
| Placebo Arm | Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks | -9.4 % change from preoperative eGFR | Standard Deviation 14 |