ATN is a multi-center, prospective, randomized, parallel-group trial of an intensive strategy versus conventional strategy of renal replacement therapy for the treatment of acute renal failure (ARF) 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 and each patient will be actively followed for 60 days.

Condition	Treatment or Intervention	Phase
Acute Renal Failure	Procedure: Renal replacement therapy	Phase III

Further Study Details: 

Expected Total Enrollment:  1164

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

Primary Outcomes: 60-day all-cause mortality.

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 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 3 years will provide a power of 0.90 to detect a reduction in mortality from 55% to 45% with a=0.05. Study enrollment began in November 2003.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

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

Arkansas
      Central Arkansas Veterans Healthcare System, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      VA San Diego Healthcare System, San Diego,  California,  92161,  United States; Recruiting
      San Francisco VAMC, San Francisco,  California,  94121,  United States; Not yet recruiting
      West Los Angeles VA Healthcare Center, Los Angeles,  California,  90073,  United States; Recruiting
      University of California, San Francisco, San Francisco,  California,  94118-1211,  United States; Not yet recruiting
Connecticut
      VACT Healthcare System, West Haven,  Connecticut,  06516,  United States; Recruiting
Florida
      University of Miami, Miami,  Florida,  33136,  United States; Recruiting
      Miami VAMC, Miami,  Florida,  33125-1693,  United States; Recruiting
Indiana
      Richard L. Roudebush VAMC, Indianapolis,  Indiana,  46202,  United States; Recruiting
Louisiana
      New Orleans VAMC, New Orleans,  Louisiana,  70146,  United States; Recruiting
Maryland
      Johns Hopkins University School of Medicine, Baltimore,  Maryland,  21205,  United States; Recruiting
Massachusetts
      Massachusetts General Hospital, Boston,  Massachusetts,  02114,  United States; Not yet recruiting
Michigan
      VA Ann Arbor Healthcare System, Ann Arbor,  Michigan,  48105,  United States; Recruiting
Missouri
      Washington University School of Medicine, St. Louis,  Missouri,  63110,  United States; Recruiting
New York
      VA Western New York Healthcare System, Buffalo,  New York,  14215,  United States; Recruiting
North Carolina
      Wake Forest University School of Medicine, Winston Salem,  North Carolina,  27157-1053,  United States; Recruiting
Ohio
      The Cleveland Clinic Foundation, Cleveland,  Ohio,  44195,  United States; Recruiting
Oregon
      Portland VAMC, Portland,  Oregon,  97207,  United States; Recruiting
Pennsylvania
      University of Pittsburgh Medical Center, Pittsburgh,  Pennsylvania,  15261,  United States; Recruiting
      VA Pittsburgh Healthcare System, Pittsburgh,  Pennsylvania,  15240,  United States; Recruiting
Tennessee
      VA Tennessee Valley Healthcare System, Nashville,  Tennessee,  37212-2637,  United States; Not yet recruiting
Texas
      University of Texas Medical School @ Houston, Houston,  Texas,  77030,  United States; Recruiting
      MD Anderson Cancer Center, Houston,  Texas,  77030,  United States; Recruiting
      VA North Texas Healthcare System, Dallas,  Texas,  75216,  United States; Recruiting
      Houston VAMC, Houston,  Texas,  77030-4298,  United States; Recruiting
Virginia
      Hunter Holmes McGuire VAMC, Richmond,  Virginia,  23249,  United States; Recruiting
Washington
      Puget Sound Healthcare System, Seattle,  Washington,  98108-1597,  United States; Recruiting
Puerto Rico
      San Juan VAMC, San Juan,  00921-3201,  Puerto Rico; Recruiting

Study ID Numbers:  530
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  January 15, 2004
ClinicalTrials.gov Identifier:  NCT00076219
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08