Acute Renal Failure Trial Network (ATN) Study (ATN)

August 16, 2013 updated by: US Department of Veterans Affairs

CSP #530 - Intensive vs. Conventional Renal Support in Acute Renal Failure

This is a multi-center, prospective, randomized, parallel-group trial of an intensive strategy vs conventional strategy of renal replacement therapy for the treatment of acute renal failure secondary to acute tubular necrosis in critically ill patients. The primary hypothesis is that the intensive strategy will reduce 60-day all cause mortality by 10% compared to the conventional strategy - i.e.,a reduction from 55% in the conventional arm to 45% in the intensive arm. Secondary outcomes are 60-day in-hospital all-cause mortality, 1-year all cause mortality, and recovery of renal function by day 28. The study will recruit 1164 patients over a period of 3 years, 8 months and each patient will be actively followed for 60 days.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Hypothesis: An intensive management strategy for renal support in critically ill patients with acute renal failure decreases mortality as compared to less intensive (conventionally recommended) management strategies for renal replacement therapy.

Secondary Hypotheses: An intensive management strategy for renal support in critically ill patients with acute renal failure will shorten the duration of ARF, decrease the incidence and duration of non-renal complications and is cost-effective as compared to less intensive (conventionally recommended) management strategies for renal replacement therapy.

Primary Outcomes: 60-day all-cause mortality.

Secondary Outcomes: All-cause hospital mortality; 1-year all cause mortality; recovery of renal function; duration of renal support (dialysis-free days); ICU and hospital length of stay (ICU-and hospital-free days); non-renal organ system failures (organ-failure-free days); and discharge to "home" not on dialysis.

Study Abstract: The optimal management of renal replacement therapy (RRT) in acute renal failure (ARF) is uncertain. The VA/NIH Acute Renal Failure Trial Network (ATN Study) is designed to test the hypothesis that a strategy of intensive renal support will decrease mortality in critically ill patients with ARF as compared to less intensive (conventionally recommended) management. In this multicenter, prospective trial, patients with ARF due to acute tubular necrosis will be randomized equally to intensive or conventional management strategies for RRT.

In both arms, RRT will be initiated using the same criteria. Hemodynamically stable patients (SOFA cardiovascular score: 0-2) will receive intermittent hemodialysis (IHD) while hemodynamically unstable patients (SOFA cardiovascular score: 3-4) will be treated with continuous venovenous hemodiafiltration (CVVHDF) or sustained low-efficiency hemodialysis (SLED). Patients will convert between modalities of therapy as hemodynamic status changes over time. The intensity of therapy in IHD and SLED will vary between groups based on treatment frequency; with treatments provided 6-times per week in the intensive management strategy arm and 3-times per week in the conventional management strategy arm. In CVVHDF, intensity of therapy will vary based on effluent flow rate with a prescribed flow rate of 35 mL/kg/hour in the intensive management strategy arm and 20 mL/kg/hour in the conventional management strategy arm.

Protocol therapy will be continued until renal function recovers or until day 28. The primary study end-point will be 60-day all-cause mortality. Other end-points will include hospital and 1-year mortality, recovery of renal function, duration of renal support, ICU and hospital length of stay, hospital discharge off of dialysis and development/recovery of non-renal organ failure. An economic analysis will be performed to assess the costs and relative cost effectiveness of the two strategies.

The planned total enrollment of 1164 patients at 27 institutions over 44 months was selected to provide a power of 0.90 to detect a reduction in mortality from 55% to 45% with alpha=0.05 assuming a dropout/loss-to-follow-up rate of 10%.

Study enrollment began in November 2003 and closed after 44 months on July 2, 2007. Total enrollment was 1124 subjects. Fewer than 3% of subjects withdrew from protocol therapy. Follow-up for the primary study endpoint (60-day all-cause mortality) concluded on August 31, 2007; one-year follow-up will conclude in July 2008.

A type of dialysis solution used in the study was under IND with No. 67,631 and granted by Center for Drug Evaluation and Research in FDA.

Study Type

Interventional

Enrollment (Actual)

1124

Phase

  • 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
    • Arkansas
      • No. Little Rock, Arkansas, United States, 72114-1706
        • Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
    • California
      • San Francisco, California, United States, 94121
        • VA Medical Center, San Francisco
      • West Los Angeles, California, United States, 90073
        • VA Greater Los Angeles Healthcare System, West LA
    • Colorado
      • Denver, Colorado, United States, 80220
        • VA Eastern Colorado Health Care System, Denver
    • Connecticut
      • West Haven, Connecticut, United States, 06516
        • VA Connecticut Health Care System (West Haven)
    • Florida
      • Miami, Florida, United States, 33125
        • VA Medical Center, Miami
    • Georgia
      • Augusta, Georgia, United States, 30904
        • VA Medical Center, Augusta
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
        • Richard Roudebush VA Medical Center, Indianapolis
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • VA Maryland Health Care System, Baltimore
    • Massachusetts
      • Boston, Massachusetts, United States, 02130
        • VA Medical Center, Jamaica Plain Campus
    • Michigan
      • Ann Arbor, Michigan, United States, 48113
        • VA Ann Arbor Healthcare System
    • Missouri
      • St Louis, Missouri, United States, 63106
        • VA Medical Center, St Louis
    • New York
      • Buffalo, New York, United States, 14215
        • VA Western New York Healthcare System at Buffalo
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157-1053
        • Wake Forest University School of Medicine
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • VA Medical Center, Cleveland
    • Oregon
      • Portland, Oregon, United States, 97201
        • VA Medical Center, Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Health Care System
    • Tennessee
      • Nashville, Tennessee, United States, 37212-2637
        • VA Medical Center
    • Texas
      • Dallas, Texas, United States, 75216
        • VA North Texas Health Care System, Dallas
      • Houston, Texas, United States, 77030
        • Michael E. DeBakey VA Medical Center (152)
    • Virginia
      • Richmond, Virginia, United States, 23249
        • Hunter Holmes McGuire VA Medical Center
    • Washington
      • Seattle, Washington, United States, 98108
        • VA Puget Sound Health Care System, Seattle

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:

  • Acute renal failure clinically consistent with a diagnosis of acute tubular necrosis
  • Plan for renal replacement therapy by clinical team
  • Receiving care in a critical care unit
  • One non-renal organ failure or sepsis
  • Age 18 or older
  • Patient or surrogate provides informed consent

Exclusion Criteria:

  • Baseline serum creatinine > 2 mg/dL (177 mol/L) in males, > 1.5 mg/dL (133 mol/L) in females
  • Acute renal failure clinically believed to be due to an etiology other than acute tubular necrosis

  • More than 72 hours since meeting both of the following conditions:

    1. Fulfillment of the definition of ARF; and
    2. BUN > 100 mg/dL (36 mmol/L)
  • More than 1 hemodialysis treatment or more than 24 hours since starting continuous renal replacement therapy
  • Prior kidney transplant
  • Pregnancy
  • Prisoner
  • Weight > 128.5 kg
  • Non-candidacy for renal replacement therapy
  • Moribund state
  • Patient not expected to survive 28 days because of underlying terminal chronic medical condition
  • Comfort-measures-only status
  • Participation in a concurrent interventional study
  • Patient/surrogate refusal
  • Physician refusal

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intensive renal replacement therapy
In the intensive management strategy, intermittent hemodialysis and sustained low-efficiency dialysis were provided 6 times per week, and continuous venovenous hemodiafiltration was provided at 35 mL/kg/hour.
Procedure: renal replacement therapy
renal replacement therapy
Active Comparator: Less-intensive renal replacement therapy
In the less-intensive management strategy, intermittent hemodialysis and sustained low-efficiency dialysis were provided 3 times per week, and continuous venovenous hemodiafiltration was provided at 20 mL/kg/hour.
Procedure: renal replacement therapy
renal replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
60-day All-cause Mortality
Time Frame: 60 days
60-day all-cause mortality
60 days

Collaborators and Investigators

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

Sponsor

US Department of Veterans Affairs

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Study Chair: Paul M. Palevsky, VA Pittsburgh Health Care System

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

October 1, 2003

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

July 1, 2008

Study Registration Dates

First Submitted

January 15, 2004

First Submitted That Met QC Criteria

January 16, 2004

First Posted (Estimate)

January 19, 2004

Study Record Updates

Last Update Posted (Estimate)

August 23, 2013

Last Update Submitted That Met QC Criteria

August 16, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 530

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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