Acute Renal Failure Trial Network (ATN) Study

Phase 3

Completed

Conditions: Acute Renal Failure

Interventions: Procedure: renal replacement therapy

Registration Number: NCT00076219

Lead Sponsor: US Department of Veterans Affairs

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1124

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive renal replacement therapy	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.
Less-intensive renal replacement therapy	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.

Primary Outcome Measures

Name	Time	Method
60-day All-cause Mortality	60 days	60-day all-cause mortality

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (22): VA Pittsburgh Health Care System
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Pittsburgh, Pennsylvania, United States
VA Connecticut Health Care System (West Haven)
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West Haven, Connecticut, United States
Richard Roudebush VA Medical Center, Indianapolis
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Indianapolis, Indiana, United States
VA Medical Center, Cleveland
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Cleveland, Ohio, United States
Michael E. DeBakey VA Medical Center (152)
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Houston, Texas, United States
VA Puget Sound Health Care System, Seattle
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Seattle, Washington, United States
Hunter Holmes McGuire VA Medical Center
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Richmond, Virginia, United States
Wake Forest University School of Medicine
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Winston-Salem, North Carolina, United States
VA North Texas Health Care System, Dallas
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Dallas, Texas, United States
VA Medical Center, Augusta
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Augusta, Georgia, United States
VA Medical Center, Miami
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Miami, Florida, United States
VA Medical Center, San Francisco
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San Francisco, California, United States
VA Eastern Colorado Health Care System, Denver
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Denver, Colorado, United States
VA Maryland Health Care System, Baltimore
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Baltimore, Maryland, United States
VA Medical Center, St Louis
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St Louis, Missouri, United States
VA Ann Arbor Healthcare System
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Ann Arbor, Michigan, United States
VA Western New York Healthcare System at Buffalo
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Buffalo, New York, United States
VA Medical Center, Portland
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Portland, Oregon, United States
VA Greater Los Angeles Healthcare System, West LA
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West Los Angeles, California, United States
Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
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No. Little Rock, Arkansas, United States
VA Medical Center, Jamaica Plain Campus
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Boston, Massachusetts, United States
VA Medical Center
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Nashville, Tennessee, United States