Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery

Effects of Endothelin Receptor Antagonist on Ischemic Kidney Injury During Nephron Sparing Surgery for Renal Mass Excision: Assessment by Ischemia Biomarkers, NGAL, KIM-1

Based on animal studies, it was found that administration of endothelial receptor antagonists before and after renal blood vessels clamp and release results in a significantly reduced renal function injury.

On the basis of these results, we chose to divide the study population into 2 groups: control group that would be treated the standard accepted preventive treatment: intravenous injection of Mannitol, cooling of the kidney surface, compared to the treatment group that in addition would receive pre- and post-operative treatment of endothelial receptor antagonists (Ambrisentan (Volibris (10mg).

To be noticed that the drug is recognized and is given as a primary indication for patients with pulmonary hypertension.

The differences between the renal function and biomarkers for pre- and post-operative renal ischemic injury would be examined in order to disclose if the kidney injury of the treated group was indeed smaller.

This information will enable us to protect the operated kidneys from the ischemic damage, especially in those patients with poor basic renal function.

Study Overview

• Status: Unknown
• Conditions: Kidney Failure, Acute
• Intervention / Treatment: Drug: Ambrisentan 10 MG

Detailed Description

This is a study aimed at examining the protective effect of endothelin antagonism on the ischemic damage the kidney undergoes during partial nephrectomy for kidney lesion removal.

In such procedure, it is common to clamp the kidney blood vessels in order to eliminate blood flow in the surgical field that will enable clear visibility to differentiate the tumor tissue from the normally kidney parenchyma.

Later, after removing the tumor lesion and suturing the tumor bed, the blockage is released and the renal blood flow returns.

The blockage itself and its release causes damage to the kidney tissue that is usually reduced by the kidney's cooling (through ice crystals)and as well as intravenous injection of mannitol.

In this study, patients were divided into 2 groups randomly, assigned the receipt in the order of recruitment.

The first group will receive the standard treatment and the other will be given before and after surgery endothelin antagonists in addition to the standard treatment. The drug will be given once a day for 5 days, starting 48 hours before surgery. Treatment efficacy assessment will be based on comparison of renal function (serum creatinine level and glomerular filtration) as well as biomarkers of acute renal damage (NGAL, KIM-1, and others) that will be taken from patients before and at different time points after surgery: urine samples to be taken at the following time points: - 3 , 8,24,48,72 hours after surgery. Blood samples will be taken at the following time points: - 8, 24, 48, 72 hours after surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 3339419
    • Bnai-Zion Medical Center
  • Haifa, Israel, 3525408
    • Department of Physiology, The Bruce and Ruth Rapapport Faculty of Medicine, Technion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with a single kidney lesion who undergo Contrast enhancement (by CT scan)
2. Normal contra-lateral kidney as illustrated by imaging tests
3. Patients eligible for anesthesia and surgery

Exclusion Criteria:

1. Patients with chronic kidney infections
2. Blood clot disorders
3. End-stage renal failure
4. Patients sensitive to the study drug
5. Patients with cardiac heart failure, EF <40%
6. Patients with hyperkalemia
7. Patients with systolic blood pressure under 90 mmHg

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treated group; Tab. Volibris 10mg given once a day for 5 days, starting 48 hours before surgery (in addition for the standard treatment for partial nephrectomy)	Drug: Ambrisentan 10 MG; be given once a day for 5 days, starting 48 hours before surgery
No Intervention: Control group; Treated with the standard treatment for partial nephrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RENAL FUNCTION INJURY	quantified by serum CRE, KIM-1,NGAL and urine markers KIM-1 NGAL	2 YEARS

Collaborators and Investigators

• Sponsor: Bnai Zion Medical Center
• Collaborators: Rambam Health Care Campus
• Investigators: Principal Investigator: Ofir Avitan, M.D., Bnai-Zion Medical Center, Haifa, Israel

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2018
• Primary Completion (Actual): February 1, 2020
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Acute Kidney Injury; Antihypertensive Agents; Ambrisentan
• Other Study ID Numbers: 0048-18-BNZ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Only the Patients index and the collected data will be provided without private names or ID numbers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No