Renal CancerPhase 3NCT01606787
Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes
A Phase 3 study testing mannitol in people with Renal Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cancer
- What is being tested?
- mannitol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 210 participants
- Where
- 1 siteUnited States
- Study dates
- 22 May 2012to Feb 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: 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.
- Conditions
- Renal Cancer
- Being tested
- mannitol, placebo
- Keywords
- Kidney, MANNITOL, PLACEBO, Partial Nephrectomy, 12-079
- Medical subject headings
- Kidney Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
mannitolDrug
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.
placeboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (1)
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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2012 (estimated)
- Study start22 May 2012
- Primary completionFeb 2018
- Study completionFeb 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Renal CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 210 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jonathan Coleman, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01606787
- Sponsor's protocol ID
- 12-079
- Status last verified
- Feb 2018
- First submitted
- 24 May 2012
- Last updated
- 15 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 28822586
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 3 Trial of Intravenous Mannitol Use During Partial Nephrectomy Prior to Renal Ischemia and Impact on Renal Function Outcomes
- ClinicalTrials.gov ID
- NCT01606787
- Acronym / sponsor ID
- 12-079
- Conditions
- Renal Cancer
- Keywords
- Kidney, MANNITOL, PLACEBO, Partial Nephrectomy, 12-079
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 210 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 22 May 2012 (actual)
- Primary completion
- Feb 2018 (actual)
- Study completion
- Feb 2018 (actual)
- First posted
- 28 May 2012 (estimated)
- Results
- Posted 12 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| mannitol arm | Experimental | Drug: mannitolThis 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 arm | Placebo comparator | Other: placeboThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| mannitolAfter 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. | Drug | mannitol arm |
| placeboAfter 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. | Other | placebo arm |
Primary outcome
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months
Time frame: 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.
1 secondary outcome
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Weeks
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28822586Spaliviero 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.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
Related trials for Renal Cancer
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruitingObservational study
Federated Learning in Renal Tumor Model
Renal Tumors
RecruitingPhase 2
Testing the Effectiveness of Two Immunotherapy Drugs (Nivolumab and Ipilimumab) With One Anti-cancer Targeted Drug (Cabozantinib) for Rare Genitourinary Tumors
Bladder Adenocarcinoma, Bladder Clear Cell Adenocarcinoma
Active, not recruiting
App-Based Mindfulness Intervention for the Improvement of Quality of Life in Patients With Metastatic Renal Cell Cancer
Metastatic Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8
RecruitingPhase 2/3
Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer
Renal Pelvis and Ureter Urothelial Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan Coleman, MD principal investigator
Memorial Sloan Kettering Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing mannitol in people with Renal Cancer, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01606787, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2018.