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

Tracking Information
First Submitted Date ICMJE	January 15, 2004
First Posted Date ICMJE	January 19, 2004
Results First Submitted Date	June 12, 2013
Results First Posted Date	August 16, 2013
Last Update Posted Date	August 23, 2013
Study Start Date ICMJE	October 2003
Actual Primary Completion Date	September 2007 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 5, 2013)	60-day All-cause Mortality [ Time Frame: 60 days ]; 60-day all-cause mortality
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00076219 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Acute Renal Failure Trial Network (ATN) Study
Official Title ICMJE	CSP #530 - Intensive vs. Conventional Renal Support in Acute Renal Failure
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Acute Renal Failure
Intervention ICMJE	Procedure: renal replacement therapy; renal replacement therapy
Study Arms	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. Intervention: Procedure: 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. Intervention: Procedure: renal replacement therapy
Publications *	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 support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20. doi: 10.1056/NEJMoa0802639. Epub 2008 May 20. Erratum in: N Engl J Med. 2009 Dec 10;361(24):2391.; 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 within the Acute Renal Failure Trial Network Study. Crit Care. 2009;13(4):310. doi: 10.1186/cc7901. Epub 2009 Aug 11.; 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.; 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 Failure Trial Network Study. Clin J Am Soc Nephrol. 2010 Aug;5(8):1366-72. doi: 10.2215/CJN.02570310. Epub 2010 May 27.; 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 Soc Nephrol. 2012 Jul;7(7):1063-70. doi: 10.2215/CJN.00450112. Epub 2012 May 17.; Ng YH, Ganta K, Davis H, Pankratz VS, Unruh M. Vascular Access Site for Renal Replacement Therapy in Acute Kidney Injury: A Post hoc Analysis of the ATN Study. Front Med (Lausanne). 2017 Apr 11;4:40. doi: 10.3389/fmed.2017.00040. eCollection 2017.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 5, 2013)	1124
Original Enrollment ICMJE; (submitted: June 23, 2005)	1164
Actual Study Completion Date	July 2008
Actual Primary Completion Date	September 2007 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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: Fulfillment of the definition of ARF; and 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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00076219
Other Study ID Numbers ICMJE	530
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	VA Office of Research and Development
Study Sponsor ICMJE	VA Office of Research and Development
Collaborators ICMJE	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators ICMJE	Study Chair: Paul M. Palevsky VA Pittsburgh Health Care System
PRS Account	VA Office of Research and Development
Verification Date	August 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP