Standard vs. Accelerated Initiation of RRT in Acute Kidney Injury (STARRT-AKI: Principal Trial)

STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI): A Multi-Centre, Randomized, Controlled Trial (Principal Trial)

The objectives of this trial are to determine whether, in critically ill patients with severe acute kidney injury (AKI), randomization to accelerated initiation of renal replacement therapy (RRT), compared to standard initiation, leads to:

1. Improved survival (primary outcome); and
2. Recovery of kidney function (principal secondary outcome), defined as independence from RRT at 90 days

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Other: Standard RRT initiation; Other: Accelerated RRT initiation

Detailed Description

Acute kidney injury (AKI) is a common and devastating complication of critical illness. Once AKI is established, treatment is largely supportive and no intervention has been found to restore kidney function or improve overall survival. Renal replacement therapy (RRT), usually in the form of hemodialysis, is frequently needed to manage patients with severe AKI. Such patients have an in-hospital mortality that consistently exceeds 50% with delays in RRT initiation implicated as a possible contributor. A recent meta-analysis suggested that earlier initiation of RRT may improve survival, but this is based on data derived overwhelmingly from observational studies. The investigators recently completed a multi-centre randomized controlled pilot trial that confirmed the feasibility of allocating patients to two different strategies of RRT initiation. Patient recruitment and follow-up, as well as patient safety, were successfully demonstrated during the pilot phase of this research program. The optimal timing of RRT initiation is an existing knowledge gap and a clear priority for investigation.

• Study Type: Interventional
• Enrollment (Actual): 3019
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Ballarat, Australia, 3350
    • Ballarat Hospital
  • Bedford Park, Australia, 5042
    • Flinder Medical Centre
  • Bendigo, Australia, 3550
    • Bendigo Hospital
  • Box Hill, Australia
    • Eastern Hospital (Box Hill and Maroondah Hospital)
  • Concord, Australia, 2139
    • Concord Hospital
  • Epping, Australia, 3076
    • The Northern Hospital
  • Geelong, Australia, 3220
    • Geelong Hospital
  • Heidelberg, Australia, 3084
    • Austin Hospital
  • Kingswood, Australia, NSW 2747
    • Nepean Hospital
  • Melbourne, Australia
    • The Alfred Hospital
  • Nambour, Australia, QLD 4560
    • Nambour General Hospital
  • St Albans, Australia, VIC 3021
    • Western Health (Footscray Hospital & Sunshine Hospital)
  • Sydney, Australia
    • Royal Prince Alfred Hospital
  • Sydney, Australia, 2065
    • Royal North Shore Hospital
  • Sydney, Australia, 2010
    • St. Vincent's Hospital
  • Woolloongabba, Australia
    • Princess Alexandra Hospital
• Austria
  • Graz, Austria, 8036
    • Medical University Graz
  • Innsbruck, Austria
    • Medical University Innsbruck
  • Wien, Austria, 1090
    • Vienna General Hospital
• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Ghent, Belgium
    • Ghent University Hospital
• Brazil
  • Rio Branco, Brazil
    • Hospital de Clínicas de Porto Alegre - Rio Grande do Sul
• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Foothills Hospital
    • Calgary, Alberta, Canada, T1Y 6J4
      • Peter Lougheed Centre
    • Edmonton, Alberta, Canada
      • Royal Alexandra Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
    • Edmonton, Alberta, Canada, T5R 4H5
      • Misericordia Community Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • Mazankowski Alberta Heart Institute
    • Edmonton, Alberta, Canada
      • Grey Nuns Community Hospital
    • Red Deer, Alberta, Canada, T4N 4E7
      • Red Deer Regional Hospital
    • St. Albert, Alberta, Canada, T8N 6C4
      • Sturgeon Community Hospital
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Surrey Memorial Hospital, Fraser Health
    • Vancouver, British Columbia, Canada
      • St. Paul's Hospital - Providence Health Care
    • Victoria, British Columbia, Canada, V8R 1J8
      • Royal Jubilee Hospital
    • Victoria, British Columbia, Canada, V8Z 6R5
      • Victoria General Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Health Sciences Centre
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3X9
      • Memorial University of Newfoundland
  • Ontario
    • Hamilton, Ontario, Canada
      • Hamilton General Hospital
    • Hamilton, Ontario, Canada
      • Juravinski Hospital
    • Hamilton, Ontario, Canada
      • St. Joseph's Healthcare Hamilton
    • Kingston, Ontario, Canada
      • Kingston General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre, University Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre, Victoria Hospital
    • Mississauga, Ontario, Canada
      • Trillium Health Partners - Credit Valley Hospital
    • Mississauga, Ontario, Canada
      • Trillium Health Partners - Mississauga Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital, Civic Campus
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital, General Campus
    • Sudbury, Ontario, Canada
      • Health Sciences North
    • Toronto, Ontario, Canada
      • Mount Sinai Hospital
    • Toronto, Ontario, Canada
      • St. Michael's Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada
      • Toronto General Hospital
    • Toronto, Ontario, Canada
      • Toronto Western Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Hôpital Maisonneuve-Rosemont
    • Montreal, Quebec, Canada
      • Centre hospitalier de l'université de Montréal (Notre Dame)
    • Montreal, Quebec, Canada
      • Centre hospitalier de l'université de Montréal (St. Luc)
    • Montreal, Quebec, Canada
      • CHUM - Hôtel Dieu Montreal
    • Montreal, Quebec, Canada
      • McGill University Health Centre (MUHC)
    • Quebec City, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ)
    • Quebec City, Quebec, Canada
      • Centre Hospitalier Universitaire de Quebec (CHUQ)
    • Sherbrooke, Quebec, Canada
      • Centre hospitalier universitaire de Sherbrooke (CHUS)
    • Trois-Rivières, Quebec, Canada
      • Centre de sante et de services sociaux de Trois-Rivieres (CIUSSS MCQ)
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • Regina Qu'Appelle Health Region
• China
  • Beijing, China
    • Beijing Friendship Hospital, Capital Medical University
  • Beijing, China
    • Peking Union Medical College Hospital
  • Changchun, China
    • The First Hospital of Jilin University
  • Changsha, China
    • Xiangya Hospital Central South University
  • Guiyang, China
    • Guizhou Provincial People's Hospital
  • Jinan, China
    • Shandong Provincial Hospital
  • Nanjing, China
    • Zhongda Hospital Southeast University
  • Wuhan, China
    • Renmin Hospital of Wuhan University
  • Wuhan, China
    • Zhongnan Hospital of Wuhan University
  • Xi'an, China
    • The First Affiliated Hospital of Xi'an Jiaotong University
  • Xiamen, China
    • The first affiliated hospital of xiamen university
  • Zhengzhou, China
    • Henan Provincial People's Hospital
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Central Hospital
  • Tampere, Finland, 33521
    • Tampere University Hospital
  • Turku, Finland, 20521
    • Turku University Hospital
• France
  • Colombes, France, 92700
    • Hôpital Louis Mourier
• Germany
  • Coburg, Germany, 96450
    • Klinikum Coburg
  • Münster, Germany, 48149
    • University Hospital Münster
• Ireland
  • Dublin, Ireland
    • St. Vincent'S University Hospital
• Italy
  • Milano, Italy, 20132
    • San Raffaele Hospital
• New Zealand
  • Auckland, New Zealand
    • Auckland Hospital DCCM
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
  • Hastings, New Zealand
    • Hawke's Bay Hospital
  • Rotorua, New Zealand
    • Rotorua Hospital
  • Wellington, New Zealand, 6021
    • Wellington Hospital
  • Auckland
    • Grafton, Auckland, New Zealand, 1148
      • Auckland City Hospital
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois (CHUV)
• United Kingdom
  • Aylesbury, United Kingdom, HP21 8AL
    • Stoke Mandeville Hospital
  • High Wycombe, United Kingdom, HP11 2TT
    • Wycombe General Hospital
  • Leeds, United Kingdom
    • Leeds Teaching Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, SE13 6LH
    • Lewisham Hospital
  • London, United Kingdom
    • Guy's and St. Thomas Hospital
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospital
  • Orpington, United Kingdom, BR6 8ND
    • Princess Royal University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University Of Kentucy
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years
2. Admission to an intensive care unit (ICU)
3. Evidence of kidney dysfunction [serum creatinine ≥100 µmol/L (women) and ≥ 130 µmol/L (men)]

4. Evidence of severe AKI defined by at least 1 of the following 3 criteria:

   i) ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during the current hospitalization; OR ii) Achievement of a serum creatinine ≥ 354 µmol/L with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during the current hospitalization; OR iii) Urine output < 6.0 mL/kg over the preceding 12 hours

Exclusion Criteria:

1. Serum potassium > 5.5 mmol/L
2. Serum bicarbonate < 15 mmol/L
3. Presence of a drug overdose that necessitates initiation of RRT
4. Lack of commitment to ongoing life support (including RRT)
5. Any RRT within the previous 2 months (either acute or chronic RRT)
6. Kidney transplant within the past 365 days
7. Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate < 20 mL/min/1.73 m2
8. Presence or clinical suspicion of renal obstruction, rapidly progressive glomerulonephritis, vasculitis, thrombotic microangiopathy or acute interstitial nephritis
9. Clinician(s) caring for patient believe(s) that immediate RRT is mandated

10. Clinician(s) caring for patient believe(s) that deferral of RRT initiation is mandated

    • at their discretion, clinicians may administer a bolus of intravenous furosemide (ie, "furosemide stress test") and evaluate the subsequent urine output to help guide decision making regarding the likelihood of AKI progression

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard RRT initiation; RRT initiation will be guided by the presence of one or more clinical indications. Even in the absence of one of these indications, RRT may be commenced at the discretion of the treating physician.	Other: Standard RRT initiation; In the absence of kidney function recovery, the initiation of RRT will be permitted if one of the following develops: serum potassium ≥ 6.0 mmol/L; pH ≤ 7.20 or serum bicarbonate ≤ 12 mmol/L; evidence of severe respiratory failure, based on a PaO2/FiO2 ≤ 200 and clinical perception of volume overload; and/or persistent AKI > 72 hours following the time of randomization.
Experimental: Accelerated RRT initiation; A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of the patient meeting the eligibility criteria.	Other: Accelerated RRT initiation; A dialysis catheter will be placed and RRT initiated as soon as possible and within 12 hours of eligibility. This 12 hour window includes the time needed to obtain consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
All-cause Mortality.	90 days following study randomization.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death in ICU		Measured in-hospital and at day 28.
EuroQoL EQ-5D-5L.	A measure of health-related quality of life and patient utility.	Measured at day 90 and at day 365.
RRT Dependence		90 days following study randomization.
Composite of Death or RRT Dependence.		90 days following study randomization.
Measurement of Estimated Glomerular Filtration Rate.		90 days following study randomization.
Measurement of Albuminuria.		90 days following study randomization.
Major Adverse Kidney Outcomes.	Defined as death, RRT dependence or sustained reduction in kidney function (defined as eGFR < 75% baseline eGFR).	90 days following study randomization.
Mechanical Ventilation-free Days.		Measured from randomization through day 28.
Vasoactive Therapy-free Days		Measured from randomization through day 28.
ICU-free Days		Measured from randomization through day 28.
Hospitalization-free Days		Measured from randomization through day 90.
Health Care Costs.		Measured from baseline through day 365.
Composite of Death or RRT Dependence.		Measured at day 365.

Collaborators and Investigators

• Sponsor: Unity Health Toronto
• Collaborators: National Health and Medical Research Council, Australia; Canadian Institutes of Health Research (CIHR); Baxter Healthcare Corporation; National Institute for Health Research, United Kingdom; The George Institute; Health Research Council, New Zealand; Medical Research Institute of New Zealand
• Investigators: Principal Investigator: Ron Wald, MDCM MPH, Unity Health Toronto; Principal Investigator: Sean M Bagshaw, MD MSc, University of Alberta

Publications and helpful links

General Publications

• STARRT-AKI Investigators. Statistical analysis plan for the Standard versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial. Crit Care Resusc. 2019 Sep;21(3):162-170.
• STARRT-AKI Investigators. STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial. Can J Kidney Health Dis. 2019 Jun 10;6:2054358119852937. doi: 10.1177/2054358119852937. eCollection 2019.
• STARRT-AKI Investigators; Canadian Critical Care Trials Group; Australian and New Zealand Intensive Care Society Clinical Trials Group; United Kingdom Critical Care Research Group; Canadian Nephrology Trials Network; Irish Critical Care Trials Group; Bagshaw SM, Wald R, Adhikari NKJ, Bellomo R, da Costa BR, Dreyfuss D, Du B, Gallagher MP, Gaudry S, Hoste EA, Lamontagne F, Joannidis M, Landoni G, Liu KD, McAuley DF, McGuinness SP, Neyra JA, Nichol AD, Ostermann M, Palevsky PM, Pettila V, Quenot JP, Qiu H, Rochwerg B, Schneider AG, Smith OM, Thome F, Thorpe KE, Vaara S, Weir M, Wang AY, Young P, Zarbock A. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med. 2020 Jul 16;383(3):240-251. doi: 10.1056/NEJMoa2000741. Erratum In: N Engl J Med. 2020 Jul 30;383(5):502. doi: 10.1056/NEJMx200016.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: October 4, 2015
• First Posted (Estimated): October 6, 2015

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: July 27, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Critical illness; Dialysis; Renal replacement therapy; Hemodialysis; Acute kidney injury
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: STARRT-AKI: Principal Trial