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

NCT01606787 | Completed Phase 3 Results

• 1 other identifier: 12-079
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cancer

Keywords

Kidney; MANNITOL; PLACEBO; Partial Nephrectomy; 12-079

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (1)

• Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks

  6 weeks

Study Arms (2)

mannitol arm

EXPERIMENTAL

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.

Drug: mannitol

placebo arm

PLACEBO COMPARATOR

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.

Other: placebo

Interventions

mannitol DRUG

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.

mannitol arm

placebo OTHER

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.

placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Spaliviero M, Power NE, Murray KS, Sjoberg DD, Benfante NE, Bernstein ML, Wren J, Russo P, Coleman JA. Intravenous Mannitol Versus Placebo During Partial Nephrectomy in Patients with Normal Kidney Function: A Double-blind, Clinically-integrated, Randomized Trial. Eur Urol. 2018 Jan;73(1):53-59. doi: 10.1016/j.eururo.2017.07.038. Epub 2017 Aug 16.

  PMID: 28822586 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Mannitol

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Dr. Jonathan Coleman, MD
• Organization: Memorial Sloan Kettering Cancer Center

colemanj@mskcc.org

646-422-4432

Study Officials

• Jonathan Coleman, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2012
• First Posted: May 28, 2012
• Study Start: May 22, 2012
• Primary Completion: February 1, 2018
• Study Completion: February 1, 2018
• Last Updated: October 15, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-02

Locations

US (1)