Acute Renal Failure Trial Network (ATN) Study

Acute Renal Failure Clinical Trial

— ATN  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00076219
• Other study ID #: 530
• Status: Completed
• Phase: Phase 3
• First received: January 15, 2004
• Last updated: August 16, 2013
• Start date: October 2003
• Est. completion date: July 2008

Study information

• Verified date: August 2013
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1124
• Est. completion date: July 2008
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Renal Failure
• Renal Insufficiency

Intervention

Procedure:
• renal replacement therapy
renal replacement therapy

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Johansen KL, Smith MW, Unruh ML, Siroka AM, O'Connor TZ, Palevsky PM; VA/NIH Acute Renal Failure Trial Network. Predictors of health utility among 60-day survivors of acute kidney injury in the Veterans Affairs/National Institutes of Health Acute Renal Fa — View Citation

Joyce VR, Smith MW, Johansen KL, Unruh ML, Siroka AM, O'Connor TZ, Palevsky PM; Veteran Affairs/National Institutes of Health Acute Renal Failure Trial Network. Health-related quality of life as a predictor of mortality among survivors of AKI. Clin J Am S — View Citation

Palevsky PM, O'Connor T, Zhang JH, Star RA, Smith MW. Design of the VA/NIH Acute Renal Failure Trial Network (ATN) Study: intensive versus conventional renal support in acute renal failure. Clin Trials. 2005;2(5):423-35. — View Citation

Palevsky PM, O'Connor TZ, Chertow GM, Crowley ST, Zhang JH, Kellum JA; US Department of Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network. Intensity of renal replacement therapy in acute kidney injury: perspective from withi — View Citation

VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O'Connor TZ, Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM, Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	60-day All-cause Mortality	60-day all-cause mortality	60 days	Yes