Delayed Renal Allograft Function and Furosemide Treatment — DRAFFT  

Delayed Graft Function Clinical Trial

Official title: DRAFFT Trial: Delayed Renal Allograft Function and Furosemide Treatment: A Randomized Prospective Double-blinded Placebo-controlled Clinical Pilot Trial

Status Withdrawn

Clinical Trial Summary

This study will be a randomized prospective double-blind placebo-controlled clinical pilot trial. This will be a single center project that will take place at Loma Linda University Medical Center. All adult kidney recipients will be informed of the study prior to operation. The Nephrology fellows or attending physicians will attempt to obtain informed consent from all eligible patients, pre-transplant. Those patients who consent will be screened post operation for enrollment. Patients who do not meet all eligibility criteria and/or who meet some exclusion criteria will be deemed ineligible for the trial, and will be excluded. The Nephrology and Transplant teams will be blinded of patient assignment and only the pharmacy will know the patient's assignment.

Clinical Trial Description

1. Background/ Rationale Kidney Transplantation is a lifesaving modality in patients with end-stage renal disease (ESRD), and the numbers of transplants have been skyrocketing since the first successful trials. In 2013 alone, there were over 18,000 kidney transplants done in the United States of America. Of those, 11,161 were from a deceased donor (NKUDIC 2011, One Legacy 2014, USRDS 2013). One common complication of renal transplants is Delayed Graft Function (DGF). DGF is a serious complication, which is best defined as the need for renal replacement therapy, such as dialysis, within the first week after renal transplant (Mallon et al. 2013). DGF greatly increases the risk of acute and chronic transplant rejection, which decreases patient survival and quality of life, for those patients who do survive (Perico et al. 2004, Weber et al. 2014). Additionally, the rate of DGF is highest in patients who have received deceased donor transplants (One Legacy 2014). Therefore, it is crucial to the well-being of this large population to reduce the incidence of DGF. Our approach is to investigate current treatment modalities for patients post-deceased donor renal transplant, to understand how best to prevent DGF before it even starts. Currently, administration of loop diuretics such as furosemide is a common practice in order to prevent and treat oliguria in renal transplant patients. However, only animal models have been able to show a benefit in treating acute kidney injury (AKI), which occurs in the transplant kidney due to cold ischemia time, with furosemide. There is a lack of evidence that furosemide use leads to improved patient outcomes in patients with AKI (Nadeau-Fredette et al. 2013). Given that side effects of furosemide administration include ototoxicity, hypotension, electrolyte abnormalities, and hypersensitivity reactions, and the investigators hypothesize, may not significantly reduce the incidence of DGF from placebo, it is important to investigate if the benefits of furosemide administration truly outweigh the harms (Strom et al. 2003). The investigators intend to achieve this by way of a randomized, double-blinded, pilot clinical trial in adult oliguric patients, post-deceased donor renal transplant.

2. Objectives

I.Primary Objective:

i.To test the hypothesis that DGF rate is the same in adult oliguric post-deceased donor renal transplant patients administered furosemide vs. placebo.

II.Secondary Objectives:

i.To compare the following within the two treatment groups:

• 30-day, 90-day and 12-month creatinine levels and estimated glomerular filtration rate (eGFR)

• The need for RRT (Hemodialysis or Peritoneal dialysis) 30 days, 90 days and 12 months post-transplant

• The time from transplant to DGF development

• The incidence of DGF

• The incidence of primary graft non-function

• Overall hospital length of stay

• The KDPI score in relation to primary graft non-function

ii. To quantify the association between furosemide administration and relevant patient centered outcomes, such as hospital length of stay and acquired complications, in order to decrease patient morbidity and mortality.

c. Study Outline

All patients that have been admitted for a deceased donor kidney transplant will be seen by the Nephrology service for pre-transplant evaluation. The Nephrology Fellow/Attending physician will go over a checklist that determines if the patient will be eligible for the study and will obtain the informed consent if the patient is eligible. Informed consent will be obtained from all eligible patients. All eligible patients' urine output will be monitored as soon as they return to the unit from the operating room. If the patient remains oliguric or anuric for 6 hours, the bedside nurse will alert the on-call study coordinator for randomization and enrollment per protocol.

Study Intervention Patients assigned to the furosemide infusion group will receive furosemide infusions, as outlined in figure 2. This has been adapted from Ostermann et al. (2007) and the SPARK study protocol (Bagshaw et al. 2010).

Furosemide will be prepared in bags that contain 1000 mg of furosemide per 250 mL of saline reaching a concentration of 4 mg/mL. All medication and placebo bags will have no identifiers that show what type of drug is being administered, for blinding purposes. Medication and placebo bags will have randomly generated study identifier numbers. The protocol in figure 2 will be followed to achieve a total urine output of 1mL/kg/h. The furosemide infusion rate will not exceed 4mg/min IV as this is the maximum set by the manufacturer. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Delayed Graft Function

• NCT number: NCT02312115
• Study type: Interventional
• Source: Loma Linda University
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 2016
• Completion date: October 2016