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

• Sponsor: Unity Health Toronto (Other)
• Overall Status: Completed
• CT.gov ID: NCT02568722
• Collaborator: Canadian Institutes of Health Research (CIHR) (Other), National Health and Medical Research Council, Australia (Other), Baxter Healthcare Corporation (Industry), The George Institute (Other), National Institute for Health Research, United Kingdom (Other), Medical Research Institute of New Zealand (Other), Health Research Council, New Zealand (Other)
• Enrollment: 3,019
• Locations: 105
• Arms: 2
• Actual Duration (Months): 50
• Patients Per Site: 28.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury	Other: Standard RRT initiation; Other: Accelerated RRT initiation	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 3019 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: STandard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI): A Multi-Centre, Randomized, Controlled Trial (Principal Trial)
• Actual Study Start Date: Oct 1, 2015
• Actual Primary Completion Date: Dec 1, 2019
• Actual Study Completion Date: Dec 1, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. All-cause mortality. [90 days following study randomization.]

Secondary Outcome Measures

1. RRT dependence [90 days following study randomization.]

2. Composite of death or RRT dependence. [90 days following study randomization.]

3. Measurement of estimated glomerular filtration rate. [90 days following study randomization.]

4. Measurement of albuminuria. [90 days following study randomization.]

5. 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).

6. Mechanical ventilation-free days. [Measured from randomization through day 28.]

7. Vasoactive therapy-free days [Measured from randomization through day 28.]

8. ICU-free days [Measured from randomization through day 28.]

9. Hospitalization-free days [Measured from randomization through day 90.]

10. Death in ICU [Measured in-hospital and at day 28.]

11. EuroQoL EQ-5D-5L. [Measured at day 90 and at day 365.]

    A measure of health-related quality of life and patient utility.

12. Health care costs. [Measured from baseline through day 365.]

13. Composite of death or RRT dependence. [Measured at day 365.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. ≥ 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Florida	Gainesville	Florida	United States	32611
3	University of Kentucy	Lexington	Kentucky	United States	40506
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Rhode Island Hospital	Providence	Rhode Island	United States	02903
6	The Miriam Hospital	Providence	Rhode Island	United States	02906
7	Ballarat Hospital	Ballarat		Australia	3350
8	Flinder Medical Centre	Bedford Park		Australia	5042
9	Bendigo Hospital	Bendigo		Australia	3550
10	Eastern Hospital (Box Hill and Maroondah Hospital)	Box Hill		Australia
11	Concord Hospital	Concord		Australia	2139
12	The Northern Hospital	Epping		Australia	3076
13	Geelong Hospital	Geelong		Australia	3220
14	Austin Hospital	Heidelberg		Australia	3084
15	Nepean Hospital	Kingswood		Australia	NSW 2747
16	The Alfred Hospital	Melbourne		Australia
17	Nambour General Hospital	Nambour		Australia	QLD 4560
18	Western Health (Footscray Hospital & Sunshine Hospital)	St Albans		Australia	VIC 3021
19	St. Vincent's Hospital	Sydney		Australia	2010
20	Royal North Shore Hospital	Sydney		Australia	2065
21	Royal Prince Alfred Hospital	Sydney		Australia
22	Princess Alexandra Hospital	Woolloongabba		Australia
23	Medical University Graz	Graz		Austria	8036
24	Medical University Innsbruck	Innsbruck		Austria
25	Vienna General Hospital	Wien		Austria	1090
26	Antwerp University Hospital	Edegem		Belgium	2650
27	Ghent University Hospital	Ghent		Belgium
28	Hospital de Clínicas de Porto Alegre - Rio Grande do Sul	Rio Branco		Brazil
29	Peter Lougheed Centre	Calgary	Alberta	Canada	T1Y 6J4
30	Foothills Hospital	Calgary	Alberta	Canada
31	Misericordia Community Hospital	Edmonton	Alberta	Canada	T5R 4H5
32	Mazankowski Alberta Heart Institute	Edmonton	Alberta	Canada	T6G 2B7
33	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
34	Grey Nuns Community Hospital	Edmonton	Alberta	Canada
35	Royal Alexandra Hospital	Edmonton	Alberta	Canada
36	Red Deer Regional Hospital	Red Deer	Alberta	Canada	T4N 4E7
37	Sturgeon Community Hospital	St. Albert	Alberta	Canada	T8N 6C4
38	Surrey Memorial Hospital, Fraser Health	Surrey	British Columbia	Canada	V3V 1Z2
39	St. Paul's Hospital - Providence Health Care	Vancouver	British Columbia	Canada
40	Royal Jubilee Hospital	Victoria	British Columbia	Canada	V8R 1J8
41	Victoria General Hospital	Victoria	British Columbia	Canada	V8Z 6R5
42	Health Sciences Centre	Winnipeg	Manitoba	Canada
43	Memorial University of Newfoundland	St. John's	Newfoundland and Labrador	Canada	A1B 3X9
44	Hamilton General Hospital	Hamilton	Ontario	Canada
45	Juravinski Hospital	Hamilton	Ontario	Canada
46	St. Joseph's Healthcare Hamilton	Hamilton	Ontario	Canada
47	Kingston General Hospital	Kingston	Ontario	Canada
48	London Health Sciences Centre, University Hospital	London	Ontario	Canada
49	London Health Sciences Centre, Victoria Hospital	London	Ontario	Canada
50	Trillium Health Partners - Credit Valley Hospital	Mississauga	Ontario	Canada
51	Trillium Health Partners - Mississauga Hospital	Mississauga	Ontario	Canada
52	Lakeridge Health	Oshawa	Ontario	Canada	L1G 2B9
53	The Ottawa Hospital, Civic Campus	Ottawa	Ontario	Canada
54	The Ottawa Hospital, General Campus	Ottawa	Ontario	Canada
55	Health Sciences North	Sudbury	Ontario	Canada
56	Mount Sinai Hospital	Toronto	Ontario	Canada
57	St. Michael's Hospital	Toronto	Ontario	Canada
58	Sunnybrook Health Sciences Centre	Toronto	Ontario	Canada
59	Toronto General Hospital	Toronto	Ontario	Canada
60	Toronto Western Hospital	Toronto	Ontario	Canada
61	Centre hospitalier de l'université de Montréal (Notre Dame)	Montreal	Quebec	Canada
62	Centre hospitalier de l'université de Montréal (St. Luc)	Montreal	Quebec	Canada
63	CHUM - Hôtel Dieu Montreal	Montreal	Quebec	Canada
64	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada
65	McGill University Health Centre (MUHC)	Montreal	Quebec	Canada
66	Institut Universitaire de Cardiologie et de Pneumologie de Québec- Université Laval (IUCPQ)	Quebec City	Quebec	Canada	G1V 4G5
67	Centre Hospitalier Universitaire de Quebec (CHUQ)	Quebec City	Quebec	Canada
68	Centre Hôspitalier universitaire de Sherbrooke (CHUS)	Sherbrooke	Quebec	Canada
69	Centre de sante et de services sociaux de Trois-Rivieres (CIUSSS MCQ)	Trois-Rivières	Quebec	Canada
70	Regina Qu'Appelle Health Region	Saskatoon	Saskatchewan	Canada
71	Beijing Friendship Hospital, Capital Medical University	Beijing		China
72	Peking Union Medical College Hospital	Beijing		China
73	The First Hospital of Jilin University	Changchun		China
74	Xiangya Hospital Central South University	Changsha		China
75	Guizhou Provincial People's Hospital	Guiyang		China
76	Shandong Provincial Hospital	Jinan		China
77	Zhongda Hospital Southeast University	Nanjing		China
78	Renmin Hospital of Wuhan University	Wuhan		China
79	Zhongnan Hospital of Wuhan University	Wuhan		China
80	The First Affiliated Hospital of Xi'An Jiaotong University	Xi'an		China
81	The First Affiliated Hospital of Xiamen University	Xiamen		China
82	Henan Provincial People's Hospital	Zhengzhou		China
83	Helsinki University Central Hospital	Helsinki		Finland	00290
84	Tampere University Hospital	Tampere		Finland	33521
85	Turku University Hospital	Turku		Finland	20521
86	Hopital Louis Mourier	Colombes		France	92700
87	Klinikum Coburg	Coburg		Germany	96450
88	University Hospital Münster	Münster		Germany	48149
89	St. Vincent's University Hospital	Dublin		Ireland
90	San Raffaele Hospital	Milano		Italy	20132
91	Auckland City Hospital	Grafton	Auckland	New Zealand	1148
92	Auckland Hospital DCCM	Auckland		New Zealand
93	Christchurch Hospital	Christchurch		New Zealand	8011
94	Hawke's Bay Hospital	Hastings		New Zealand
95	Rotorua Hospital	Rotorua		New Zealand
96	Wellington Hospital	Wellington		New Zealand	6021
97	Centre Hospitalier Universitaire Vaudois (CHUV)	Lausanne		Switzerland	1011
98	Stoke Mandeville Hospital	Aylesbury		United Kingdom	HP21 8AL
99	Wycombe General Hospital	High Wycombe		United Kingdom	HP11 2TT
100	Leeds Teaching Hospital	Leeds		United Kingdom
101	Lewisham Hospital	London		United Kingdom	SE13 6LH
102	King's College Hospital	London		United Kingdom	SE5 9RS
103	Guy's and St. Thomas Hospital	London		United Kingdom
104	Nottingham University Hospital	Nottingham		United Kingdom	NG5 1PB
105	Princess Royal University Hospital	Orpington		United Kingdom	BR6 8ND

Sponsors and Collaborators

• Unity Health Toronto
• Canadian Institutes of Health Research (CIHR)
• National Health and Medical Research Council, Australia
• Baxter Healthcare Corporation
• The George Institute
• National Institute for Health Research, United Kingdom
• Medical Research Institute of New Zealand
• Health Research Council, New Zealand

Investigators

• Principal Investigator: Ron Wald, MDCM MPH, Unity Health Toronto
• Principal Investigator: Sean M Bagshaw, MD MSc, University of Alberta

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Unity Health Toronto
• ClinicalTrials.gov Identifier: NCT02568722
• Other Study ID Numbers: STARRT-AKI: Principal Trial
• First Posted: Oct 6, 2015
• Last Update Posted: Jan 22, 2020
• Last Verified: Jan 1, 2020

• Keywords provided by Unity Health Toronto: Renal replacement therapy; Acute kidney injury; Dialysis; Hemodialysis; Critical illness
• Additional relevant MeSH terms: Acute Kidney Injury; Wounds and Injuries

Study Results

No Results Posted as of Jan 22, 2020