Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01606787
First received: May 24, 2012
Last updated: August 19, 2014
Last verified: August 2014

May 24, 2012
August 19, 2014
May 2012
May 2015   (final data collection date for primary outcome measure)
difference in eGFR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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.
difference in eGFR [ Time Frame: 6 months ] [ Designated as safety issue: No ]
The difference will be assessed with an ANCOVA model with eGFR 6 months after surgery (+/- 1 month) 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.
Complete list of historical versions of study NCT01606787 on ClinicalTrials.gov Archive Site
difference in eGFR [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
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.
difference in eGFR [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
between treatment groups at 6 weeks (+/- 2 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.
Not Provided
Not Provided
 
Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes
Phase 3 Trial of Intravenous Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Renal Cancer
  • Drug: 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.
  • Other: 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.
  • Experimental: 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.
    Intervention: Drug: mannitol
  • Placebo Comparator: 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.
    Intervention: Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
192
May 2015
May 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Jonathan Coleman, MD 646-422-4432
Contact: Karim Touijer, MD 646-422-4486
United States
 
NCT01606787
12-079
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Not Provided
Principal Investigator: Jonathan Coleman, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP