Clinical trial NCT02568722: Standard vs. Accelerated Initiation of RRT in Acute Kidney Injury (STARRT-AKI: Principal Trial)
Official title: STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI): A Multi-Centre, Randomized, Controlled Trial (Principal Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Keywords: Renal replacement therapy
Acute kidney injury
Dialysis
Hemodialysis
Critical illness
Lead sponsor: Unity Health Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: National Health and Medical Research Council, Australia
name: Baxter Healthcare Corporation
name: The George Institute
name: National Institute for Health Research, United Kingdom
name: Medical Research Institute of New Zealand
name: Health Research Council, New Zealand
First posted: 2015-10-06
Enrollment: 3019
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: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause Mortality.
timeFrame: 90 days following study randomization.
Secondary outcomes:
measure: RRT Dependence
timeFrame: 90 days following study randomization.
measure: Composite of Death or RRT Dependence.
timeFrame: 90 days following study randomization.
measure: Measurement of Estimated Glomerular Filtration Rate.
timeFrame: 90 days following study randomization.
measure: Measurement of Albuminuria.
timeFrame: 90 days following study randomization.
measure: Major Adverse Kidney Outcomes.
timeFrame: 90 days following study randomization.
measure: Mechanical Ventilation-free Days.
timeFrame: Measured from randomization through day 28.
measure: Vasoactive Therapy-free Days
timeFrame: Measured from randomization through day 28.
measure: ICU-free Days
timeFrame: Measured from randomization through day 28.
measure: Hospitalization-free Days
timeFrame: Measured from randomization through day 90.
measure: Death in ICU
timeFrame: Measured in-hospital and at day 28.
measure: EuroQoL EQ-5D-5L.
timeFrame: Measured at day 90 and at day 365.
measure: Health Care Costs.
timeFrame: Measured from baseline through day 365.
measure: Composite of Death or RRT Dependence.
timeFrame: Measured at day 365.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Lexington
country: United States
facility: University of Kentucy
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Ballarat
country: Australia
facility: Ballarat Hospital
city: Bedford Park
country: Australia
facility: Flinder Medical Centre
city: Bendigo
country: Australia
facility: Bendigo Hospital
city: Box Hill
country: Australia
facility: Eastern Hospital (Box Hill and Maroondah Hospital)
city: Concord
country: Australia
facility: Concord Hospital
city: Epping
country: Australia
facility: The Northern Hospital
city: Geelong
country: Australia
facility: Geelong Hospital
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Kingswood
country: Australia
facility: Nepean Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Nambour
country: Australia
facility: Nambour General Hospital
city: St Albans
country: Australia
facility: Western Health (Footscray Hospital & Sunshine Hospital)
city: Sydney
country: Australia
facility: St. Vincent's Hospital
city: Sydney
country: Australia
facility: Royal North Shore Hospital
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Graz
country: Austria
facility: Medical University Graz
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Wien
country: Austria
facility: Vienna General Hospital
city: Edegem
country: Belgium
facility: Antwerp University Hospital
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Rio Branco
country: Brazil
facility: Hospital de Clínicas de Porto Alegre - Rio Grande do Sul
city: Calgary
country: Canada
facility: Peter Lougheed Centre
state: Alberta
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Misericordia Community Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Mazankowski Alberta Heart Institute
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Community Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Red Deer
country: Canada
facility: Red Deer Regional Hospital
state: Alberta
city: St. Albert
country: Canada
facility: Sturgeon Community Hospital
state: Alberta
city: Surrey
country: Canada
facility: Surrey Memorial Hospital, Fraser Health
state: British Columbia
city: Vancouver
country: Canada
facility: St. Paul's Hospital - Providence Health Care
state: British Columbia
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Victoria
country: Canada
facility: Victoria General Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre
state: Manitoba
city: St. John's
country: Canada
facility: Memorial University of Newfoundland
state: Newfoundland and Labrador
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare Hamilton
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre, University Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre, Victoria Hospital
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Mississauga Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, Civic Campus
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital, General Campus
state: Ontario
city: Sudbury
country: Canada
facility: Health Sciences North
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Toronto Western Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre hospitalier de l'université de Montréal (Notre Dame)
state: Quebec
city: Montreal
country: Canada
facility: Centre hospitalier de l'université de Montréal (St. Luc)
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Hôtel Dieu Montreal
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre (MUHC)
state: Quebec
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ)
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec (CHUQ)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre Hôspitalier universitaire de Sherbrooke (CHUS)
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre de sante et de services sociaux de Trois-Rivieres (CIUSSS MCQ)
state: Quebec
city: Saskatoon
country: Canada
facility: Regina Qu'Appelle Health Region
state: Saskatchewan
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
city: Jinan
country: China
facility: Shandong Provincial Hospital
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'An Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Colombes
country: France
facility: Hopital Louis Mourier
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Münster
country: Germany
facility: University Hospital Münster
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Milano
country: Italy
facility: San Raffaele Hospital
city: Grafton
country: New Zealand
facility: Auckland City Hospital
state: Auckland
city: Auckland
country: New Zealand
facility: Auckland Hospital DCCM
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Hastings
country: New Zealand
facility: Hawke's Bay Hospital
city: Rotorua
country: New Zealand
facility: Rotorua Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
city: Aylesbury
country: United Kingdom
facility: Stoke Mandeville Hospital
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital
city: London
country: United Kingdom
facility: Lewisham Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: London
country: United Kingdom
facility: Guy's and St. Thomas Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital
city: Orpington
country: United Kingdom
facility: Princess Royal University Hospital
Study officials:
affiliation: Unity Health Toronto
name: Ron Wald, MDCM MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Alberta
name: Sean M Bagshaw, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.