Vasodilators and Anti-Oxidant Therapy in Early ATN

March 25, 2016 updated by: Southeast Renal Research Institute

Combination Fenoldopam Mesylate and Intravenous MESNA (2-mercaptoethane Sulphonate)in Early Acute Kidney Injury (AKD): A Randomized, Double-Blind Placebo Controlled Clinical Trial

Patients developing kidney failure after open heart surgery experience an abrupt decrease in blood flow to the kidney. The investigators hypothesize that administration of fenoldopam mesylate (a drug that increases blood flow to the kidney) to patients early in the course of their disease could reduce progression to dialysis-dependent acute renal failure. The investigators also hypothesize that restoring blood flow could induce additional injury to the kidney through the release of reactive oxygen species. Therefore, patients in this protocol will be randomized to receive a fenoldopam or the anti-oxidant MESNA. The investigators hypothesize that combination treatment with Fenoldopam and MESNA will decrease the incidence of death or dialysis at 21 days in patients with early post-operative acute renal failure.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Primary Hypotheses:

  • Combination therapy with intravenous fenoldopam mesylate and MESNA will reduce the incidence of dialysis and all cause mortality at 21 days in patients with established acute tubular necrosis (ATN).
  • The combination of fenoldopam mesylate and Intravenous MESNA reduces the level of reactive oxygen species released following restoration of renal blood flow in patients with ischemic ATN.

Specific Aims

  1. To conduct a multicenter, double blind, trial comparing the efficacy of a 72-hour infusion of fenoldopam mesylate or combination of fenoldopam plus intravenous MESNA to reduce the incidence of dialysis or all-cause mortality at 21 days in patients with ischemic ATN.
  2. To determine the effects of fenoldopam mesylate alone or in combination with MESNA on reperfusion injury as evidenced by changes in the level of urinary 15-F2t-isoprostanes The rational is that failure of parenteral vasodilators to reduce the incidence of death or dialysis among patients with ATN may involve the extension of tubular injury through normalization of renal blood flow and subsequent reperfusion injury. Moreover, the generation of reactive oxidative species in areas of hypoxia could blunt impair regional blood flow in the kidney through inhibition of nitric oxide production.
  3. To serially measure the urinary content of ICAM-1, VCAM-1, KIM-1, P-selectin, E-selectin, MCP-1and Cyr-61 and determine the ability of specific markers to identify patients progressing to dialysis dependent ATN.

The rational is that ICAM-1 is expressed by ischemic endothelium and facilitates neutrophile migration into areas of necrotic epithelium. We will determine whether rising urinary ICAM-1 will identify patients with progressive dialysis-dependent ATN. Specific aim #3 will also examine whether a reduction in dialysis or all cause mortality by fenoldopam mesylate correlates with reduced urinary expression of ICAM-1 or other cell adhesion molecules. The serum, plasma, urine supernatant and urinary casts obtained from patients enrolled in this trial will be made available to other investigators involved in the study of early ATN.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, District of Columbia, United States, 20037
        • Chawala, M. MD
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Mandeep Grewal

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Post-operative patients with serum creatinine (Cr) rising 0.3 mg/dl or more than 25% above admission levels within a single 24-hour period will be considered eligible.
  • Central Venous Access: [CVP > 6 cm H2O without mechanical ventilation] [CVP > 9 cm H2O with mechanical ventilation]

  • Mean arterial pressure > 70 mm Hg receiving up to two vasopressors including:

    • Nor-epinephrine (0.01-1.5g/kg/min)
    • Phenylephrine (0.1-7.0g/kg/min
    • Vasopressin (0.1-1.5 mU/kg/min)

Exclusion Criteria:

  • Patients with APACHE scores greater than 30 (or felt by the principal investigators to be unlikely survive more than 24 hours).
  • Patients requiring 3 or more presser agents to maintain a MAP of 70 mm Hg or greater.
  • Patients on two vasopressors with a MAP < 70 mm Hg will not be considered for enrollment
  • Patient with baseline serum Cr > 3.0 mg/dl
  • Patients with known bacteremia and/or the Systemic Inflammatory Response Syndrome (SIRS)
  • Patients ATN secondary to aminoglycosides or amphotericin B or equivalent anti-fungal drug
  • Patients on chronic peritoneal or hemodialysis
  • Patients receiving acute peritoneal or hemodialysis during current hospitalization
  • Patients on dopamine infusion within the previous 12 hours
  • Patients with known HIV seropositivity and past history of opportunistic infection
  • Pregnant or lactating women
  • Patients with history of uncontrolled atrial or ventricular cardiac arrhythmia
  • Patients under the influence of alcohol or other drugs
  • Patients enrolled in a previous investigational study within15 days of enrollment
  • Patients with a known hypersensitivity to fenoldopam mesylate
  • Patients with a known history of glaucoma.
  • Patients with cirrhosis of the liver and/or portal hypertension
  • Patients with toxic levels of calcineurin inhibitors (FK-506 or CsA) or acute allograft rejection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of Death or Dialysis at 21 days

Secondary Outcome Measures

Outcome Measure
Peak serum Cr and Duration of ICU stay

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southeast Renal Research Institute

Collaborators

Dialysis Clinic, Inc.

Investigators

  • Principal Investigator: James A Tumlin, MD, Southeast Renal Research Institute
  • Study Director: Micheal Kutner, Ph.D., Rollins School Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

October 1, 2008

Study Completion (Actual)

October 1, 2008

Study Registration Dates

First Submitted

February 1, 2006

First Submitted That Met QC Criteria

February 1, 2006

First Posted (Estimate)

February 3, 2006

Study Record Updates

Last Update Posted (Estimate)

March 28, 2016

Last Update Submitted That Met QC Criteria

March 25, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MCAT-1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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