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

Acute Kidney Injury Clinical 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02568722
• Other study ID #: STARRT-AKI: Principal Trial
• Status: Completed
• Phase: N/A
• Start date: October 2015
• Est. completion date: December 2019

Study information

• Verified date: January 2020
• Source: St. Michael's Hospital, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3019
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	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	Royal North Shore Hospital	Sydney
Australia	Royal Prince Alfred Hospital	Sydney
Australia	St. Vincent's Hospital	Sydney
Australia	Princess Alexandra Hospital	Woolloongabba
Austria	Medical University Graz	Graz
Austria	Medical University Innsbruck	Innsbruck
Austria	Vienna General Hospital	Wien
Belgium	Antwerp University Hospital	Edegem
Belgium	Ghent University Hospital	Ghent
Brazil	Hospital de Clínicas de Porto Alegre - Rio Grande do Sul	Rio Branco
Canada	Foothills Hospital	Calgary	Alberta
Canada	Peter Lougheed Centre	Calgary	Alberta
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Canada	Mazankowski Alberta Heart Institute	Edmonton	Alberta
Canada	Misericordia Community Hospital	Edmonton	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
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	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	Lakeridge Health	Oshawa	Ontario
Canada	The Ottawa Hospital, Civic Campus	Ottawa	Ontario
Canada	The Ottawa Hospital, General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec (CHUQ)	Quebec City	Quebec
Canada	Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ)	Quebec City	Quebec
Canada	Red Deer Regional Hospital	Red Deer	Alberta
Canada	Regina Qu'Appelle Health Region	Saskatoon	Saskatchewan
Canada	Centre Hôspitalier universitaire de Sherbrooke (CHUS)	Sherbrooke	Quebec
Canada	Sturgeon Community Hospital	St. Albert	Alberta
Canada	Memorial University of Newfoundland	St. John's	Newfoundland and Labrador
Canada	Health Sciences North	Sudbury	Ontario
Canada	Surrey Memorial Hospital, Fraser Health	Surrey	British Columbia
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 de sante et de services sociaux de Trois-Rivieres (CIUSSS MCQ)	Trois-Rivières	Quebec
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
China	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
Finland	Helsinki University Central Hospital	Helsinki
Finland	Tampere University Hospital	Tampere
Finland	Turku University Hospital	Turku
France	Hopital Louis Mourier	Colombes
Germany	Klinikum Coburg	Coburg
Germany	University Hospital Münster	Münster
Ireland	St. Vincent's University Hospital	Dublin
Italy	San Raffaele Hospital	Milano
New Zealand	Auckland Hospital DCCM	Auckland
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Auckland City Hospital	Grafton	Auckland
New Zealand	Hawke's Bay Hospital	Hastings
New Zealand	Rotorua Hospital	Rotorua
New Zealand	Wellington Hospital	Wellington
Switzerland	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne
United Kingdom	Stoke Mandeville Hospital	Aylesbury
United Kingdom	Wycombe General Hospital	High Wycombe
United Kingdom	Leeds Teaching Hospital	Leeds
United Kingdom	Guy's and St. Thomas Hospital	London
United Kingdom	King's College Hospital	London
United Kingdom	Lewisham Hospital	London
United Kingdom	Nottingham University Hospital	Nottingham
United Kingdom	Princess Royal University Hospital	Orpington
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Florida	Gainesville	Florida
United States	University of Kentucy	Lexington	Kentucky
United States	Rhode Island Hospital	Providence	Rhode Island
United States	The Miriam Hospital	Providence	Rhode Island
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (8)

Lead Sponsor	Collaborator
St. Michael's Hospital, Toronto	Baxter Healthcare Corporation, Canadian Institutes of Health Research (CIHR), Health Research Council, New Zealand, Medical Research Institute of New Zealand, National Health and Medical Research Council, Australia, National Institute for Health Research, United Kingdom, The George Institute

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality.		90 days following study randomization.
Secondary	RRT dependence		90 days following study randomization.
Secondary	Composite of death or RRT dependence.		90 days following study randomization.
Secondary	Measurement of estimated glomerular filtration rate.		90 days following study randomization.
Secondary	Measurement of albuminuria.		90 days following study randomization.
Secondary	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.
Secondary	Mechanical ventilation-free days.		Measured from randomization through day 28.
Secondary	Vasoactive therapy-free days		Measured from randomization through day 28.
Secondary	ICU-free days		Measured from randomization through day 28.
Secondary	Hospitalization-free days		Measured from randomization through day 90.
Secondary	Death in ICU		Measured in-hospital and at day 28.
Secondary	EuroQoL EQ-5D-5L.	A measure of health-related quality of life and patient utility.	Measured at day 90 and at day 365.
Secondary	Health care costs.		Measured from baseline through day 365.
Secondary	Composite of death or RRT dependence.		Measured at day 365.