Acute Renal Failure Trial Network (ATN) Study

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-10-31

Study Completion Date

2008-07-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Renal Failure

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Acute Renal Failure Renal Replacement Therapy multi-site randomization trial Hemodialysis Hemofiltration Critical Illness Hemodiafiltration

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Group Type EXPERIMENTAL

renal replacement therapy

Intervention Type PROCEDURE

renal replacement therapy

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.

Group Type ACTIVE_COMPARATOR

renal replacement therapy

Intervention Type PROCEDURE

renal replacement therapy

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

renal replacement therapy

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Paul M. Palevsky

Role: STUDY_CHAIR

VA Pittsburgh Health Care System

PMID: 28443283 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

530

Identifier Type: -

Identifier Source: org_study_id

Acute Renal Failure Trial Network (ATN) Study

Study Results

Basic Information

Brief Summary

Detailed Description

Conditions

Keywords

Study Design

Study Groups

Intensive renal replacement therapy

renal replacement therapy

Less-intensive renal replacement therapy

renal replacement therapy

Interventions

renal replacement therapy

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

US Department of Veterans Affairs

Responsible Party

Principal Investigators

Paul M. Palevsky

Locations

Central Arkansas VHS Eugene J. Towbin Healthcare Ctr, Little Rock

VA Medical Center, San Francisco

VA Greater Los Angeles Healthcare System, West LA

VA Eastern Colorado Health Care System, Denver

VA Connecticut Health Care System (West Haven)

VA Medical Center, Miami

VA Medical Center, Augusta

Richard Roudebush VA Medical Center, Indianapolis

VA Maryland Health Care System, Baltimore

VA Medical Center, Jamaica Plain Campus

VA Ann Arbor Healthcare System

VA Medical Center, St Louis

VA Western New York Healthcare System at Buffalo

Wake Forest University School of Medicine

VA Medical Center, Cleveland

VA Medical Center, Portland

VA Pittsburgh Health Care System

VA Medical Center

VA North Texas Health Care System, Dallas

Michael E. DeBakey VA Medical Center (152)

Hunter Holmes McGuire VA Medical Center

VA Puget Sound Health Care System, Seattle

Countries

References

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.

Kwong YD, Liu KD, Hsu CY, Cooper B, Palevsky PM, Kellum JA, Johansen KL, Miaskowski C. Subgroups of Patients with Distinct Health Utility Profiles after AKI. Kidney360. 2023 Jul 1;4(7):881-889. doi: 10.34067/KID.0000000000000201. Epub 2023 Jun 26.

Fayad AI, Buamscha DG, Ciapponi A. Timing of kidney replacement therapy initiation for acute kidney injury. Cochrane Database Syst Rev. 2022 Nov 23;11(11):CD010612. doi: 10.1002/14651858.CD010612.pub3.

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.

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.

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.

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.

Other Identifiers

530