Norepinephrine Infusion Combined With Goal-directed Fluid Therapy in Patients Undergoing Kidney Transplantations

Norepinephrine Infusion Combined With Goal-directed Fluid Therapy Reduces Delayed Graft Function Incidence in Patients Undergoing Kidney Transplantations: a Randomized Multicenter Clinical Trial

Delayed graft function (DGF), delineated by the necessity for dialytic intervention within the initial week post-transplantation, afflicts approximately 20%-50% of recipients. The primary objective of this study is to investigate the potential efficacy of norepinephrine infusion in conjunction with goal-directed fluid therapy (GDFT) in mitigating the occurrence of DGF among individuals undergoing kidney transplantations. The findings of this investigation have the potential to advance the field of perioperative care in kidney transplantations by providing insights into optimized management strategies.

Study Overview

• Status: Recruiting
• Conditions: End Stage Renal Disease; Kidney Transplantation; Delayed Graft Function
• Intervention / Treatment: Drug: Goal-Directed Fluid Therapy (GDFT); Drug: Regular Fluid Therapy

Detailed Description

Chronic kidney disease (CKD) presents a formidable challenge to global healthcare systems. With ongoing advancements in surgical techniques, kidney transplantation has emerged as a principal therapeutic modality for individuals afflicted with end stage renal disease (ESRD), markedly enhancing their long-term prognosis and overall quality of life postoperatively. Nevertheless, the occurrence of delayed graft function (DGF) represents a prevalent early complication following kidney transplantations, mainly stemming from the ischemia-reperfusion injury incurred by the transplanted kidneys and the utilization of extended criteria donor organs. The manifestation of DGF can precipitate primary allograft nonfunction, acute rejection episodes, and potentially fatal outcomes. Vigilant attention to perioperative fluid management emerges as a cornerstone in mitigating the risk of DGF. Recent strides in goal-directed fluid therapy (GDFT) have garnered substantial attention within critical care contexts, with empirical evidence underscoring its favorable impact on postoperative outcomes in critically ill cohorts. However, the efficacy of GDFT specifically in the context of kidney transplantation remains a subject of ongoing debate and scrutiny. Hence, the imperative arises to investigate potential strategies aimed at attenuating the incidence of DGF in this patient demographic.

• Study Type: Interventional
• Enrollment (Estimated): 380
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Diansan Su, Dr.; Phone Number: +862168383702; Email: diansansu@yahoo.com
• Study Contact Backup: Name: Muyan Shi, B.S.; Phone Number: +862168383702; Email: jsqdsmy@163.com

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Not yet recruiting
      • the First Affiliated Hospital of Zhengzhou University
      • Contact: Jianjun Yang, Dr.
  • Liaoning
    • Shenyang, Liaoning, China, 110016
      • Not yet recruiting
      • General Hospital of Northern Theatre Command
      • Contact: Yugang Diao, Dr.
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • RenJi Hospital
      • Contact: Muyan Shi, B.S.; Phone Number: +862168383702; Email: jsqdsmy@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Recipients aged 18 years or older
2. Scheduled to undergo kidney transplantations under general anesthesia
3. Cadaveric kidney transplantations
4. Sign the informed consent form

Exclusion Criteria:

1. Donors aged under 18 years
2. Donor kidneys classified as Maastricht category I or II
3. Contraindications to radial artery catheterization
4. Pregnancy
5. Cardiac dysfunction (exercise tolerance less than 4 METS)
6. Severe liver dysfunction (Child Pugh C-grade)
7. Respiratory diseases with tidal volume intolerance exceeding 8ml/kg
8. Severe arrhythmias, including atrial fibrillation, frequent atrial or ventricular premature beats, moderate or severe aortic and mitral regurgitation
9. Double-kidney transplantations
10. Simultaneous organ or additional surgeries during kidney transplantations
11. Repeat kidney transplantations
12. Concurrent participation in other clinical trials
13. Patients deemed ineligible by researchers

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Goal-Directed Fluid Therapy (GDFT) group; Following anesthesia induction, patients will be connected to the FlowTrac/Vigileo monitoring system to facilitate the recording of pertinent hemodynamic parameters, including stroke volume variation (SVV), stroke volume, and cardiac output. Then, Norepinephrine Infusion Combined with Goal-directed Fluid Therapy will be administered. Efforts are made to sustain a mean arterial pressure (MAP) of ≥ 80 mmHg.	Drug: Goal-Directed Fluid Therapy (GDFT); Norepinephrine will be administered intravenously at a rate of 0.06 µg/kg/min, followed by the implementation of fluid therapy guided by SVV until reaching our target. In instances where SVV ≤ 13%, indicative of adequate effective circulating blood volume, the fluid infusion rate will be adjusted to 1 ml/kg/h. Conversely, if SVV > 13%, denoting inadequate effective circulating blood volume, a rapid infusion of 1 ml/kg of crystalloid fluid will be administered over 2 minutes, with subsequent observation of fluid reactivity after a further 2-minute interval. This process is reiterated until SVV ≤ 13% is attained. Should SVV > 13% recurs during surgery, the aforementioned intervention is repeated.; Other Names: GDFT
Active Comparator: Regular Fluid Therapy group; Patients will not undergo monitoring with the FlowTrac/Vigileo system throughout the whole procedure. Anesthesiologists will rely on their clinical expertise and intraoperative circulatory hemodynamic assessment to regulate fluid infusion rates and administer medications as necessary to sustain a mean arterial pressure (MAP) of ≥ 80 mmHg until the conclusion of the surgical procedure.	Drug: Regular Fluid Therapy; Anesthesiologists will rely on their clinical expertise and intraoperative circulatory hemodynamic assessment to regulate fluid infusion rates and administer medications as necessary

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of delayed graft function (DGF)	The need for dialytic intervention within the initial week post-transplantation	Patients will be followed from postoperative day 1 to 7.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The area under the curve of serum creatinine levels from postoperative day 1 to 7	The area under the curve of serum creatinine levels from postoperative day 1 to 7	Patients will be followed from postoperative day 1 to 7.
Duration of DGF	The interval from surgery completion to the last dialysis up to 84 days post-surgery	Patients will be followed from surgery completion to the last dialysis up to 84 days post-surgery.
Number of dialysis sessions during postoperative hospitalization	Number of dialysis sessions during postoperative hospitalization	Patients will be followed from surgery completion to discharge，an average of 20 days.
Total urine output on the second postoperative day	Total urine output on the second postoperative day	Patients will be followed on the second postoperative day.
Duration of intensive care unit (ICU) stay	Duration of intensive care unit (ICU) stay	Patients will be followed during Intensive care unit (ICU) stay, an average of 2 days.
Length of hospitalization	Length of hospitalization	Patients will be followed from hospitalization to discharge, an average of 20 days.
Incidence of readmission within 30 days post-discharge	Incidence of readmission within 30 days post-discharge	Patients will be followed from discharge to 30 days after discharge.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of acute rejection during hospitalization	The incidence of acute rejection during hospitalization	Patients will be followed from surgery completion to discharge, an average of 20 days.
The survival rates of transplanted kidneys at the one-year postoperative mark	The survival rates of transplanted kidneys at the one-year postoperative mark	Patients will be followed from surgery completion to one year after surgery.
The survival rates of transplanted patients at the one-year postoperative mark	The survival rates of transplanted patients at the one-year postoperative mark	Patients will be followed from surgery completion to one year after surgery.
The occurrence of adverse events (AEs)	The occurrence of adverse events (AEs) recorded by the common terminology criteria for adverse events (CTCAE) 5.0	Patients will be followed from surgery completion to discharge, an average of 20 days.

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Diansan Su, Dr., Department of Anesthesiology Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: April 15, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Randomized controlled trial; Norepinephrine; Goal-directed fluid therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Failure, Chronic; Delayed Graft Function
• Other Study ID Numbers: LY2023-135-A

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No