Clinical trial NCT00076219: Acute Renal Failure Trial Network (ATN) Study
Official title: CSP #530 - Intensive vs. Conventional Renal Support in Acute Renal Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Renal Failure
Keywords: Acute Renal Failure
Renal Replacement Therapy
multi-site randomization trial
Hemodialysis
Hemofiltration
Critical Illness
Hemodiafiltration
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2004-01-19
Enrollment: 1124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 60-day All-cause Mortality
timeFrame: 60 days
Secondary outcomes:
Other outcomes:
Locations:
city: No. Little Rock
country: United States
facility: Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock
state: Arkansas
city: San Francisco
country: United States
facility: VA Medical Center, San Francisco
state: California
city: West Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, West LA
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Health Care System, Denver
state: Colorado
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
city: Miami
country: United States
facility: VA Medical Center, Miami
state: Florida
city: Augusta
country: United States
facility: VA Medical Center, Augusta
state: Georgia
city: Indianapolis
country: United States
facility: Richard Roudebush VA Medical Center, Indianapolis
state: Indiana
city: Baltimore
country: United States
facility: VA Maryland Health Care System, Baltimore
state: Maryland
city: Boston
country: United States
facility: VA Medical Center, Jamaica Plain Campus
state: Massachusetts
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: St Louis
country: United States
facility: VA Medical Center, St Louis
state: Missouri
city: Buffalo
country: United States
facility: VA Western New York Healthcare System at Buffalo
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cleveland
country: United States
facility: VA Medical Center, Cleveland
state: Ohio
city: Portland
country: United States
facility: VA Medical Center, Portland
state: Oregon
city: Pittsburgh
country: United States
facility: VA Pittsburgh Health Care System
state: Pennsylvania
city: Nashville
country: United States
facility: VA Medical Center
state: Tennessee
city: Dallas
country: United States
facility: VA North Texas Health Care System, Dallas
state: Texas
city: Houston
country: United States
facility: Michael E. DeBakey VA Medical Center (152)
state: Texas
city: Richmond
country: United States
facility: Hunter Holmes McGuire VA Medical Center
state: Virginia
city: Seattle
country: United States
facility: VA Puget Sound Health Care System, Seattle
state: Washington
Study officials:
affiliation: VA Pittsburgh Health Care System
name: Paul M. Palevsky
role: STUDY_CHAIR
References:
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 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.
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 within the Acute Renal Failure Trial Network Study. Crit Care. 2009;13(4):310. doi: 10.1186/cc7901. Epub 2009 Aug 11.
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. doi: 10.1191/1740774505cn116oa.
citation: 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.
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 Soc Nephrol. 2012 Jul;7(7):1063-70. doi: 10.2215/CJN.00450112. Epub 2012 May 17.
citation: Naorungroj T, Neto AS, Wang A, Gallagher M, Bellomo R. Renal outcomes according to renal replacement therapy modality and treatment protocol in the ATN and RENAL trials. Crit Care. 2022 Sep 6;26(1):269. doi: 10.1186/s13054-022-04151-5.
citation: Tsujimoto Y, Miki S, Shimada H, Tsujimoto H, Yasuda H, Kataoka Y, Fujii T. Non-pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2021 Sep 14;9(9):CD013330. doi: 10.1002/14651858.CD013330.pub2.
citation: Sharma S, Kelly YP, Palevsky PM, Waikar SS. Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation: Secondary Analysis of the Acute Renal Failure Trial Network Study. Chest. 2020 Oct;158(4):1473-1481. doi: 10.1016/j.chest.2020.05.542. Epub 2020 May 26.
citation: 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.