Trial Outcomes & Findings for Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes (NCT NCT01606787)
NCT ID: NCT01606787
Last Updated: 2018-10-15
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
210 participants
Primary outcome timeframe
6 months
Results posted on
2018-10-15
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
105
|
105
|
|
Overall Study
COMPLETED
|
101
|
98
|
|
Overall Study
NOT COMPLETED
|
4
|
7
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
4
|
5
|
|
Overall Study
Surgery canceled
|
0
|
2
|
Baseline Characteristics
Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes
Baseline characteristics by cohort
| Measure |
Mannitol Arm
n=101 Participants
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.
|
Placebo Arm
n=98 Participants
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.
|
Total
n=199 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
56 years
n=7 Participants
|
58 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
81 Participants
n=5 Participants
|
80 Participants
n=7 Participants
|
161 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
10 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
101 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
199 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsThe 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.
Outcome measures
| Measure |
Mannitol Arm
n=101 Participants
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.
|
Placebo Arm
n=99 Participants
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.
|
|---|---|---|
|
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months
|
-8.5 % change from preoperative eGFR
Standard Deviation 14
|
-8.4 % change from preoperative eGFR
Standard Deviation 12
|
SECONDARY outcome
Timeframe: 6 weeksbetween 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.
Outcome measures
| Measure |
Mannitol Arm
n=101 Participants
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.
|
Placebo Arm
n=99 Participants
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.
|
|---|---|---|
|
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks
|
-6.2 % change from preoperative eGFR
Standard Deviation 13
|
-9.4 % change from preoperative eGFR
Standard Deviation 14
|
Adverse Events
Mannitol Arm
Serious events: 19 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo Arm
Serious events: 11 serious events
Other events: 7 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Mannitol Arm
n=101 participants at risk
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.
|
Placebo Arm
n=98 participants at risk
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.
|
|---|---|---|
|
Metabolism and nutrition disorders
Dehydration
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Gastrointestinal disorders
Enterocolitis
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
General disorders
Fever
|
2.0%
2/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Flank Pain
|
2.0%
2/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Vascular disorders
Hematoma
|
2.0%
2/101 • 6 months
|
2.0%
2/98 • 6 months
|
|
Renal and urinary disorders
Hematuria
|
2.0%
2/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Injury, poisoning and procedural complications
Postoperative Hemorrhage
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Renal and urinary disorders
Urinary Fistula
|
0.99%
1/101 • 6 months
|
2.0%
2/98 • 6 months
|
|
Renal and urinary disorders
Urinary Retention
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Infections and infestations
Urinary tract infection
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Infections and infestations
Wound infection
|
3.0%
3/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Injury, poisoning and procedural complications
Injury/poison & proced complications Other, spec
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Nervous system disorders
Seizure
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
Other adverse events
| Measure |
Mannitol Arm
n=101 participants at risk
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.
|
Placebo Arm
n=98 participants at risk
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.
|
|---|---|---|
|
Renal and urinary disorders
Urinary Fistula
|
0.99%
1/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
General disorders
Fever
|
0.99%
1/101 • 6 months
|
0.00%
0/98 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Injury, poisoning and procedural complications
Injury/poison & proced complications Other, spec
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Infections and infestations
Wound infection
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
|
General disorders
Edema limbs
|
0.00%
0/101 • 6 months
|
1.0%
1/98 • 6 months
|
Additional Information
Dr. Jonathan Coleman, MD
Memorial Sloan Kettering Cancer Center
Phone: 646-422-4432
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place