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

Not Applicable

Completed

• Conditions: Acute Kidney Injury
• Interventions: Other: Standard RRT initiation; Other: Accelerated RRT initiation

• Registration Number: NCT02568722
• Lead Sponsor: Unity Health Toronto

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.

Study Timeline

• Study First Submitted: 2015-09-29
• Study Start: 2015-10
• Study First Submitted QC: 2015-10-04
• Study First Posted: 2015-10-06
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Results First Submitted: 2023-02-15
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-27
• Last Update Submitted: 2024-07-27
• Results First Posted: 2024-10-18
• Last Update Posted: 2024-10-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3019

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard RRT initiation	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.
Accelerated RRT initiation	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.

Primary Outcome Measures

Name	Time	Method
All-cause Mortality.	90 days following study randomization.

Secondary Outcome Measures

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

Trial Locations

Locations (105)

Concord Hospital; 🇦🇺 Concord, Australia

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Kentucy; 🇺🇸 Lexington, Kentucky, United States

Ballarat Hospital; 🇦🇺 Ballarat, Australia

Flinder Medical Centre; 🇦🇺 Bedford Park, Australia

Eastern Hospital (Box Hill and Maroondah Hospital); 🇦🇺 Box Hill, Australia

Bendigo Hospital; 🇦🇺 Bendigo, 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

Hospital de Clínicas de Porto Alegre - Rio Grande do Sul; 🇧🇷 Rio Branco, Brazil

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

St. Paul's Hospital - Providence Health Care; 🇨🇦 Vancouver, British Columbia, Canada

Health Sciences Centre; 🇨🇦 Winnipeg, Manitoba, Canada

Juravinski Hospital; 🇨🇦 Hamilton, Ontario, Canada

London Health Sciences Centre, Victoria Hospital; 🇨🇦 London, Ontario, Canada

The Ottawa Hospital, General Campus; 🇨🇦 Ottawa, Ontario, Canada

Trillium Health Partners - Credit Valley Hospital; 🇨🇦 Mississauga, Ontario, Canada

Lakeridge Health; 🇨🇦 Oshawa, Ontario, Canada

The Ottawa Hospital, Civic Campus; 🇨🇦 Ottawa, Ontario, Canada

Health Sciences North; 🇨🇦 Sudbury, 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

Centre hospitalier de l'université de Montréal (Notre Dame); 🇨🇦 Montreal, Quebec, Canada

CHUM - Hôtel Dieu Montreal; 🇨🇦 Montreal, Quebec, Canada

Hopital Maisonneuve-Rosemont; 🇨🇦 Montreal, Quebec, Canada

Centre hospitalier de l'université de Montréal (St. Luc); 🇨🇦 Montreal, Quebec, Canada

Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ); 🇨🇦 Quebec City, Quebec, Canada

Centre Hospitalier Universitaire de Quebec (CHUQ); 🇨🇦 Quebec City, 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

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, China

Guizhou Provincial People's Hospital; 🇨🇳 Guiyang, China

Zhongda Hospital Southeast University; 🇨🇳 Nanjing, China

Shandong Provincial Hospital; 🇨🇳 Jinan, China

Zhongnan Hospital of Wuhan University; 🇨🇳 Wuhan, China

Renmin Hospital of Wuhan University; 🇨🇳 Wuhan, China

Henan Provincial People's Hospital; 🇨🇳 Zhengzhou, China

Helsinki University Central Hospital; 🇫🇮 Helsinki, Finland

Hopital Louis Mourier; 🇫🇷 Colombes, France

University Hospital Münster; 🇩🇪 Münster, Germany

Klinikum Coburg; 🇩🇪 Coburg, Germany

Auckland Hospital DCCM; 🇳🇿 Auckland, New Zealand

San Raffaele Hospital; 🇮🇹 Milano, Italy

Auckland City Hospital; 🇳🇿 Grafton, 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

Stoke Mandeville Hospital; 🇬🇧 Aylesbury, United Kingdom

Wycombe General Hospital; 🇬🇧 High Wycombe, United Kingdom

Leeds Teaching Hospital; 🇬🇧 Leeds, United Kingdom

King's College Hospital; 🇬🇧 London, United Kingdom

Lewisham 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

Medical University Graz; 🇦🇹 Graz, Austria

University of Florida; 🇺🇸 Gainesville, Florida, United States

Ghent University Hospital; 🇧🇪 Ghent, Belgium

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

The Miriam Hospital; 🇺🇸 Providence, Rhode Island, United States

Medical University Innsbruck; 🇦🇹 Innsbruck, Austria

Vienna General Hospital; 🇦🇹 Wien, Austria

Antwerp University Hospital; 🇧🇪 Edegem, Belgium

Royal Jubilee Hospital; 🇨🇦 Victoria, British Columbia, Canada

Victoria General Hospital; 🇨🇦 Victoria, British Columbia, Canada

Surrey Memorial Hospital, Fraser Health; 🇨🇦 Surrey, British Columbia, Canada

Regina Qu'Appelle Health Region; 🇨🇦 Saskatoon, Saskatchewan, Canada

Tampere University Hospital; 🇫🇮 Tampere, Finland

Turku University Hospital; 🇫🇮 Turku, Finland

St. Vincent's University Hospital; 🇮🇪 Dublin, Ireland

Centre Hospitalier Universitaire Vaudois (CHUV); 🇨🇭 Lausanne, Switzerland

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

The First Hospital of Jilin University; 🇨🇳 Changchun, China

Xiangya Hospital Central South University; 🇨🇳 Changsha, China

The First Affiliated Hospital of Xi'An Jiaotong University; 🇨🇳 Xi'an, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Xiamen, China

Peter Lougheed Centre; 🇨🇦 Calgary, Alberta, Canada

Foothills Hospital; 🇨🇦 Calgary, Alberta, Canada

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada

McGill University Health Centre (MUHC); 🇨🇦 Montreal, Quebec, Canada

Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

London Health Sciences Centre, University Hospital; 🇨🇦 London, Ontario, Canada

Trillium Health Partners - Mississauga Hospital; 🇨🇦 Mississauga, Ontario, Canada

Memorial University of Newfoundland; 🇨🇦 St. John's, Newfoundland and Labrador, Canada

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States

St. Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada