Vasodilators and Anti-Oxidant Therapy in Early ATN

This study has been withdrawn prior to enrollment.
(The study was terminated due to logistics at a local hospital.)
Sponsor:
Collaborator:
Dialysis Clinic, Inc.
Information provided by:
Southeast Renal Research Institute
ClinicalTrials.gov Identifier:
NCT00286403
First received: February 1, 2006
Last updated: July 20, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Acute Renal Failure
Drug: Fenoldopam Mesylate and/or MESNA
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Combination Fenoldopam Mesylate and Intravenous MESNA (2-mercaptoethane Sulphonate)in Early Acute Kidney Injury (AKD): A Randomized, Double-Blind Placebo Controlled Clinical Trial

Resource links provided by NLM:


Further study details as provided by Southeast Renal Research Institute:

Primary Outcome Measures:
  • Incidence of Death or Dialysis at 21 days

Secondary Outcome Measures:
  • Peak serum Cr and Duration of ICU stay

Estimated Enrollment: 630
Study Start Date: August 2008
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00286403

Locations
United States, District of Columbia
Chawala, M. MD
Washington, District of Columbia, United States, 20037
United States, Tennessee
Mandeep Grewal
Chattanooga, Tennessee, United States, 37403
Sponsors and Collaborators
Southeast Renal Research Institute
Dialysis Clinic, Inc.
Investigators
Principal Investigator: James A Tumlin, MD Southeast Renal Research Institute
Study Director: Micheal Kutner, Ph.D. Rollins School Public Health
  More Information

Publications:
Responsible Party: James A. Tumlin, MD, Southeast Renal Research Institute
ClinicalTrials.gov Identifier: NCT00286403     History of Changes
Other Study ID Numbers: MCAT-1
Study First Received: February 1, 2006
Last Updated: July 20, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Southeast Renal Research Institute:
Acute Tubular Necrosis
antioxidants
Fenoldopam

Additional relevant MeSH terms:
Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Mesna
Antioxidants
Fenoldopam
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Vasodilator Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 24, 2014