Goal-directed Hemodynamic Management and Acute Kidney Injury After Radical Nephrectomy

Sponsor

Peking University First Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05149196

Collaborator

(none)

788

Enrollment

Location

Arms

Anticipated Duration (Months)

11.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Radical nephrectomy is a standard operation for the treatment of renal cell carcinoma. However, acute kidney injury frequently occur after surgery. And the occurrence of acute kidney injury is associated with an increased risk of chronic kidney disease. Intraoperative hypotension is identified as an important risk factor of postoperative acute kidney injury. Preliminary studies showed that goal-directed hemodynamic management may reduce organ injury after surgery but requires further demonstration. We hypothesized that goal-directed hemodynamic therapy achieved by combining liquid therapy and vasopressors can reduce the incidence of acute kidney injury after radical nephrectomy. The purpose of this study was to investigate the effect of goal-directed hemodynamic management on the incidence of acute kidney injury in patients following radical nephrectomy.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Carcinoma Nephrectomy Hemodynamic Management Acute Kidney Injury Chronic Kidney Diseases	Other: Targeted blood pressure management Other: Routine care	N/A

Detailed Description

Renal cancer accounts for 20.3% of urinary system tumors, and the incidence is still increasing. Surgical resection is the main treatment of renal cancer; radical nephrectomy is the standard operation. Acute kidney injury (AKI) is a common complication after radical nephrectomy, with an incidence of up to 53.9%. AKI is associated with the development of chronic kidney disease (CKD) and is an independent risk factor of new onset CKD in patients without underlying kidney disease. A meta-analysis showed that one year after surgery, patients with AKI had a 2.7-fold increased risk of new onset or progression of CKD and a 4.8-fold increased risk of end-stage renal disease. Moreover, even mild AKI is associated with renal insufficiency 1-2 years after surgery. Taking active measures to reduce the incidence of AKI may improve long-term renal function after radical nephrectomy.

Many clinical studies show that intraoperative hypotension is an important risk factor of postoperative kidney injury. For example, a study found that intraoperative mean arterial pressure (MAP) <65 mmHg or a decrease of more than 20% from baseline was associated with an increased risk of postoperative AKI; the risk of AKI increased alone with prolonged duration of hypotension. A recent randomized controlled trial showed that, compared with routine intraoperative blood pressure management, goal-directed hemodynamic management reduced the incidence of organ injury from 63.4% to 46.3% within 30 days after surgery. A meta-analysis included 65 randomized controlled trials with 9308 patients and observed the effect of goal-directed hemodynamic management on postoperative AKI. The results showed that a combination of fluid therapy with vasopressors reduced the incidence of AKI in high-risk patients following major abdominal or orthopedic surgery.

In a previous pilot trial of the authors, goal-directed hemodynamic management reduced the incidence of AKI by about 40% in patients following partial nephrectomy. However, the difference was not statistically significant due to insufficient sample size. The purpose of this trial is to investigate whether goal-directed intraoperative hemodynamic management can reduce the incidence of acute kidney injury in patients undergoing radical nephrectomy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

788 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

Impact of Goal-directed Hemodynamic Management on the Incidence of Acute Kidney Injury and Long-term Outcomes in Patients Undergoing Radical Nephrectomy: A Randomized Clinical Trial

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Targeted blood pressure management During anesthesia, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; For patients admitted to intensive care unit after surgery, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; In the general ward, systolic blood pressure is maintained ≥110 mmHg or within 10% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or norepinephrine infusion.	Other: Targeted blood pressure management During anesthesia, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; For patients admitted to intensive care unit after surgery, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; In the general ward, systolic blood pressure is maintained ≥110 mmHg or within 10% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or norepinephrine infusion.
Active Comparator: Routine care During anesthesia, mean blood pressure is maintained ≥65 mmHg or within 20% of baseline according to routine practice; For patients admitted to intensive care unit, mean blood pressure is maintained ≥65 mmHg or within 20% of baseline according to routine practice; In the general ward, management is performed according to routine practice.	Other: Routine care In the general ward, management is performed according to routine practice.

Arm

Intervention/Treatment

Experimental: Targeted blood pressure management

During anesthesia, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; For patients admitted to intensive care unit after surgery, mean blood pressure is maintained ≥85 mmHg or above baseline by combining fluid challenge and norepinephrine infusion; In the general ward, systolic blood pressure is maintained ≥110 mmHg or within 10% of baseline by delaying antihypertensive resumption, providing fluid challenge, and/or norepinephrine infusion.

Other: Targeted blood pressure management

Active Comparator: Routine care

During anesthesia, mean blood pressure is maintained ≥65 mmHg or within 20% of baseline according to routine practice; For patients admitted to intensive care unit, mean blood pressure is maintained ≥65 mmHg or within 20% of baseline according to routine practice; In the general ward, management is performed according to routine practice.

Other: Routine care

In the general ward, management is performed according to routine practice.

Outcome Measures

Primary Outcome Measures

Incidence of acute kidney injury [Up to 3 days after surgery]
Acute kidney injury is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.

Secondary Outcome Measures

Classification of acute kidney injury [Up to 3 days after surgery]
Classification of acute kidney injury is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria.
Proportion of intensive care unit after surgery [Up to 30 days after surgery]
Proportion of intensive care unit after surgery
Incidence of postoperative complications [Up to 30 days after surgery]
Postoperative complications are defined as new-onset medical conditions that are harmful to patients' recovery and required therapeutic intervention, i.e., grade 2 or higher on the Clavien-Dindo classification.
Length of hospital stay after surgery [Up to 30 days after surgery]
Length of hospital stay after surgery
Chronic kidney disease free survival time [Up to 3 years after surgery]
Time interval from the end of surgery to new onset of chronic kidney disease (stage 3 or above) or all-cause death, which ever come first. Chronic kidney disease is defined as glomerular filtration rate <60 ml/min/1.73 m2.
Event free survival [Up to 3 years after surgery]
Time interval from the end of surgery to new-onset chronic kidney disease (stage 3 or above), serious events (required hospitalization or reoperation), or all-cause death, which ever come first.
Overall survival time [Up to 3 years after surgery]
Time interval from the end of surgery to all-cause death.

Other Outcome Measures

Quality of life of survivors at 1, 2, and 3 years after surgery [Up to 3 years after surgery]
Quality of life is assessed with the World Health Organization Quality of Life brief version (WHOQOL-BREF). This is a 24-item questionnaire that assesses the quality of life in physical, psychological, and social relationship, and environmental domains. The score ranges from 0 to 100 for each domain, with higher score indicating better function.
Proportion of intensive care unit admission with endotracheal intubation [Up to 30 days after surgery]
Proportion of intensive care unit admission with endotracheal intubation
Length of stay in intensive care unit after surgery [Up to 30 days after surgery]
Length of stay in intensive care unit after surgery
Pain severity after surgery [UP to 3 days after surgery]
Pain severity is assessed with the numeric rating scale. This is a 11-point scale with 0= no pain and 10=the worst pain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Age of 18 years or older;
Scheduled to undergo radical nephrectomy for renal cancer.

Exclusion criteria

Refused to participate;
Diagnosed with chronic kidney disease (stage 3 or higher) before surgery;
Uncontrolled severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg);
Unable to communicate due to severe dementia, language barrier, or end-stage disease before surgery;
Enrolled in other trials;
Other conditions that are considered unsuitable for inclusion (specific reasons should be indicated).