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

NCT ID: NCT02568722

Last Updated: 2024-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 3019 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2019-12-31

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.

Conditions

Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Standard RRT initiation

Intervention Type: OTHER

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.

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.

Group Type: EXPERIMENTAL

Accelerated RRT initiation

Intervention Type: OTHER

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

National Health and Medical Research Council, Australia

OTHER

Sponsor Role: collaborator

Baxter Healthcare Corporation

INDUSTRY

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: collaborator

National Institute for Health Research, United Kingdom

OTHER_GOV

Sponsor Role: collaborator

Medical Research Institute of New Zealand

OTHER

Sponsor Role: collaborator

Health Research Council, New Zealand

OTHER

Sponsor Role: collaborator

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ron Wald, MDCM MPH

Role: PRINCIPAL_INVESTIGATOR

Unity Health Toronto

Sean M Bagshaw, MD MSc

Role: PRINCIPAL_INVESTIGATOR

University of Alberta

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Florida

Gainesville, Florida, United States

University of Kentucy

Lexington, Kentucky, United States

Mayo Clinic

Rochester, Minnesota, United States

Rhode Island Hospital

Providence, Rhode Island, United States

The Miriam Hospital

Providence, Rhode Island, United States

Ballarat Hospital

Ballarat, , Australia

Flinder Medical Centre

Bedford Park, , Australia

Bendigo Hospital

Bendigo, , Australia

Eastern Hospital (Box Hill and Maroondah Hospital)

Box Hill, , Australia

Concord Hospital

Concord, , Australia

The Northern Hospital

Epping, , Australia

Geelong Hospital

Geelong, , Australia

Austin Hospital

Heidelberg, , Australia

Nepean Hospital

Kingswood, , Australia

The Alfred Hospital

Melbourne, , Australia

Nambour General Hospital

Nambour, , Australia

Western Health (Footscray Hospital & Sunshine Hospital)

St Albans, , Australia

St. Vincent's Hospital

Sydney, , Australia

Royal North Shore Hospital

Sydney, , Australia

Royal Prince Alfred Hospital

Sydney, , Australia

Princess Alexandra Hospital

Woolloongabba, , Australia

Medical University Graz

Graz, , Austria

Medical University Innsbruck

Innsbruck, , Austria

Vienna General Hospital

Vienna, , Austria

Antwerp University Hospital

Edegem, , Belgium

Ghent University Hospital

Ghent, , Belgium

Hospital de Clínicas de Porto Alegre - Rio Grande do Sul

Rio Branco, , Brazil

Peter Lougheed Centre

Calgary, Alberta, Canada

Foothills Hospital

Calgary, Alberta, Canada

Misericordia Community Hospital

Edmonton, Alberta, Canada

Mazankowski Alberta Heart Institute

Edmonton, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

Grey Nuns Community Hospital

Edmonton, Alberta, Canada

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Red Deer Regional Hospital

Red Deer, Alberta, Canada

Sturgeon Community Hospital

St. Albert, Alberta, Canada

Surrey Memorial Hospital, Fraser Health

Surrey, British Columbia, Canada

St. Paul's Hospital - Providence Health Care

Vancouver, British Columbia, Canada

Royal Jubilee Hospital

Victoria, British Columbia, Canada

Victoria General Hospital

Victoria, British Columbia, Canada

Health Sciences Centre

Winnipeg, Manitoba, Canada

Memorial University of Newfoundland

St. John's, Newfoundland and Labrador, Canada

Health Sciences North

Greater Sudbury, Ontario, Canada

Hamilton General Hospital

Hamilton, Ontario, Canada

Juravinski Hospital

Hamilton, Ontario, Canada

St. Joseph's Healthcare Hamilton

Hamilton, Ontario, Canada

Kingston General Hospital

Kingston, Ontario, Canada

London Health Sciences Centre, University Hospital

London, Ontario, Canada

London Health Sciences Centre, Victoria Hospital

London, Ontario, Canada

Trillium Health Partners - Credit Valley Hospital

Mississauga, Ontario, Canada

Trillium Health Partners - Mississauga Hospital

Mississauga, Ontario, Canada

Lakeridge Health

Oshawa, Ontario, Canada

The Ottawa Hospital, Civic Campus

Ottawa, Ontario, Canada

The Ottawa Hospital, General Campus

Ottawa, 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

Toronto, Ontario, 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

Hopital Maisonneuve-Rosemont

Montreal, Quebec, Canada

McGill University Health Centre (MUHC)

Montreal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ)

Québec, Quebec, Canada

Centre Hospitalier Universitaire de Quebec (CHUQ)

Québec, Quebec, Canada

Centre Hôspitalier universitaire de Sherbrooke (CHUS)

Sherbrooke, Quebec, Canada

Centre de sante et de services sociaux de Trois-Rivieres (CIUSSS MCQ)

Trois-Rivières, Quebec, Canada

Regina Qu'Appelle Health Region

Saskatoon, Saskatchewan, Canada

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Peking Union Medical College Hospital

Beijing, , China

The First Hospital of Jilin University

Changchun, , China

Xiangya Hospital Central South University

Changsha, , China

Guizhou Provincial People's Hospital

Guiyang, , China

Shandong Provincial Hospital

Jinan, , China

Zhongda Hospital Southeast University

Nanjing, , China

Renmin Hospital of Wuhan University

Wuhan, , China

Zhongnan Hospital of Wuhan University

Wuhan, , China

The First Affiliated Hospital of Xi'An Jiaotong University

Xi'an, , China

The First Affiliated Hospital of Xiamen University

Xiamen, , China

Henan Provincial People's Hospital

Zhengzhou, , China

Helsinki University Central Hospital

Helsinki, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Hospital

Turku, , Finland

Hopital Louis Mourier

Colombes, , France

Klinikum Coburg

Coburg, , Germany

University Hospital Münster

Münster, , Germany

St. Vincent's University Hospital

Dublin, , Ireland

San Raffaele Hospital

Milan, , Italy

Auckland City Hospital

Grafton, Auckland, New Zealand

Auckland Hospital DCCM

Auckland, , New Zealand

Christchurch Hospital

Christchurch, , New Zealand

Hawke's Bay Hospital

Hastings, , New Zealand

Rotorua Hospital

Rotorua, , New Zealand

Wellington Hospital

Wellington, , New Zealand

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, , Switzerland

Stoke Mandeville Hospital

Aylesbury, , United Kingdom

Wycombe General Hospital

High Wycombe, , United Kingdom

Leeds Teaching Hospital

Leeds, , United Kingdom

Lewisham Hospital

London, , United Kingdom

King's College Hospital

London, , United Kingdom

Guy's and St. Thomas Hospital

London, , United Kingdom

Nottingham University Hospital

Nottingham, , United Kingdom

Princess Royal University Hospital

Orpington, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Brazil; Canada; China; Finland; France; Germany; Ireland; Italy; New Zealand; Switzerland; United Kingdom

References

McCoy IE, Liu KD, Ghamarian E, Quenot JP, Zarbock A, Bihorac A, Khoo B, Gallagher MP, Du B, Joannidis M, Kashani K, Tolwani A, Bagshaw SM, Wald R; STandard versus Accelerated initiation of Renal Replacement Therapy in AKI (STARRT-AKI) Investigators. Dialysis Dependence in Standard versus Accelerated Initiation of KRT in AKI: A Post Hoc Analysis. Clin J Am Soc Nephrol. 2025 May 1;20(5):601-607. doi: 10.2215/CJN.0000000672. Epub 2025 Mar 11.

Reference Type: DERIVED

PMID: 40232884 (View on PubMed)

Zampieri FG, Serpa-Neto A, Wald R, Bellomo R, Bagshaw SM; STARRT-AKI and RENAL Investigators. Hierarchical endpoints in critical care: A post-hoc exploratory analysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury and the intensity of continuous renal-replacement therapy in critically ill patients trials. J Crit Care. 2024 Aug;82:154767. doi: 10.1016/j.jcrc.2024.154767. Epub 2024 Mar 11.

Reference Type: DERIVED

PMID: 38461657 (View on PubMed)

Vaara ST, Serpa Neto A, Bellomo R, Adhikari NKJ, Dreyfuss D, Gallagher M, Gaudry S, Hoste E, Joannidis M, Pettila V, Wang AY, Kashani K, Wald R, Bagshaw SM, Ostermann M; STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Investigators. Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis. Crit Care Explor. 2024 Feb 19;6(2):e1053. doi: 10.1097/CCE.0000000000001053. eCollection 2024 Feb.

Reference Type: DERIVED

PMID: 38380940 (View on PubMed)

Wald R, Kirkham B, daCosta BR, Ghamarian E, Adhikari NKJ, Beaubien-Souligny W, Bellomo R, Gallagher MP, Goldstein S, Hoste EAJ, Liu KD, Neyra JA, Ostermann M, Palevsky PM, Schneider A, Vaara ST, Bagshaw SM. Fluid balance and renal replacement therapy initiation strategy: a secondary analysis of the STARRT-AKI trial. Crit Care. 2022 Nov 24;26(1):360. doi: 10.1186/s13054-022-04229-0.

Reference Type: DERIVED

PMID: 36424662 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36416787 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32668114 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31462203 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31218013 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

STARRT-AKI: Principal Trial

Identifier Type: -

Identifier Source: org_study_id