Early RRT in AKI After Cardiac Surgery

Acute Kidney Injury Clinical Trial

Official title:

Early Application of Renal-Replacement Therapy in Patients With Acute Kidney Injury After Cardiac Surgery: A Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05175053
• Other study ID #: D-2107-213-1239
• Status: Recruiting
• Phase: N/A
• Start date: December 24, 2021
• Est. completion date: September 30, 2025

Study information

• Verified date: April 2023
• Source: Seoul National University Hospital
• Contact: Ho Young Hwang, MD, PhD
• Phone: 82-2-2072-3020
• Email: scalpel[@]hanmail.net
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Acute kidney injury (AKI) is one of the major complications after cardiac surgery that may affects 20% to 40% of patients according to the definitions. Also, AKI after cardiac surgery is associated with high morbidity and mortality, with eight-fold increase in the odds ratio of death when renal replacement therapy (RRT) is required. However the indication and the optimal timing of RRT initiation are still controversial.

We hypothesized that a strategy of early initiation of RRT would result in a lower risk of surgical mortality than a standard strategy in post cardiac surgery patients with AKI of Kidney Disease: Improving Global Outcomes (KDIGO) classification stage 2 (serum creatinine, 2.0 times the baseline level; urine output, <0.5mL/kg/h for 6 or more hours).

Description:

This trial was designed as a multi-center randomized, controlled trial to recruit 202 patients who develop acute kidney injury (AKI) described as Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (serum creatinine, 2.0 times the baseline level; urine output, <0.5mL/kg/h for 6 or more hours) after cardiac surgery. Patients were randomized in a 1:1 ratio to 1 of the 2 treatment groups (Early vs. Delayed renal replacement therapy (RRT)) using a computerized system.

Sample size determination : power calculation were performed based on the primary end point (operative mortality). The expected operative mortality in the control group with delayed initiation of RRT was 55% based on the literature. Differences between treatment groups were to be detected with a power of 80%, if the operative mortality of with early initiation of RRT was 35% or less. The expected treatment effect of 20% was calculated on the mortality differences between early and delayed RRT reported in previous studies. A required sample size for the final analysis was 101 patients per treatment group, 202 patients in total (level of significance, α = 0.05; type II error, β= 0.02; potential dropouts= 5%).

Early RRT was initiated within 6 hours of diagnosis of stage 2 AKI.

Delayed RRT was initiated if any one of the following absolute indications for RRT is present

• serum urea level higher than 100mg/dL and/or with uremic encephalopathy

• serum potassium level higher than 6mmol/L and/or with electrocardiography abnormalities

• urine production lower than 0.3mL/kg/hr for 24 hours

• pH of 7.15 or less and/or severe hypotension due to metabolic acidosis

• organ edema in the presence of AKI resistant to diuretic treatment.

The primary end point is operative mortality (described as any death, regardless of cause, occurring (1) within 30 days after surgery in or out of the hospital, and (2) after 30 days during the same hospitalization subsequent to the operation).

The secondary end points included 90 day overall survival, cardiovascular mortality, RRT dependence, and major adverse kidney events (MAKE), adverse events related to RRT or vascular access, duration of mechanical ventilator support and intensive care unit stay, and hospital length of stay.

RRT delivery

: Once RRT was initiated, both groups were treated using continuous venovenous hemodiafiltration (CVVHDF) with identical settings. Initial target dose of hemodiafiltration was 25 to 50mL/kg/hr depends on the decision of attending physician and further adjusted according to the metabolic needs of the patient. Replacement fluid was delivered into the extracorporeal circuit before the filter with a ratio of dialysate to replacement fluid of 1:1. Blood flow was maintained between 100 to 250mL/min. Regional anticoagulation with nafamostat (dosage 20-50mg/hr) was used to prevent circuit clotting if necessary.

RRT was discontinued if renal recovery defined by urine output (>1mL/Kg/hr for 8 hours or more or >1000mL/24h without diuretics; >2000mL/24h with diuretics) and creatinine clearance (>20mL/min) occurred.

If cessation criteria were not fulfilled after 7 days, conversion to intermittent hemodialysis would be considered.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 202
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

• Patients within 7 days after cardiac surgery

• Acute kidney injury (AKI) described as Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 (urine output <0.5mL/kg/h for =6h or 2-fold increase in serum creatinine compared with baseline)

Exclusion Criteria:

• previous renal replacement therapy

• AKI secondary to obstructive nephropathy

• previous kidney transplantation

Related Conditions & MeSH terms

• Acute Kidney Injury

Intervention

Other:
• Renal replacement therapy
Continuous renal replacement therapy using continuous venovenous hemodiafiltration (CVVHDF)
• Best medical management
The best medical management continues until the patient meets absolute indication of renal replacement therapy

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Seoul National University Bundang Hospital

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with operative mortality	any death, regardless of cause, occurring (1) within 30 days after surgery in or out of the hospital, and (2) after 30 days during the same hospitalization subsequent to the operation	at postoperative 30 days
Secondary	Overall survival	overall survival	at postoperative 90 days
Secondary	Number of participants with cardiovascular mortality	Any death related to cardiac events, including sudden death during follow-up	at postoperative 90 days
Secondary	Number of participants with renal replacement therapy dependency	Number of participants who still needs renal replacement therapy at 90 days after operation.	at postoperative 90 days
Secondary	Number of participants with major adverse kidney events (MAKE)	MAKE indicates the composite of death, need of renal replacement therapy, and persistent renal dysfunction.	at postoperative 90 days
Secondary	Number of participants with renal replacement therapy related morbidity	adverse events related to renal replacement therapy (RRT) or vascular access for RRT.	at postoperative 90 days
Secondary	Duration of mechanical ventilation	duration of mechanical ventilator support	at postoperative 30 days
Secondary	Duration of intensive care unit stay	duration of intensive care unit stay	at postoperative 30 days
Secondary	Hospital length of stay	hospital length of stay	at postoperative 30 days