Volatile Anesthetic Protection Of Renal Transplants 2 (VAPOR-2)

To compare the effect of a sevoflurane based anesthesia versus a propofol based anesthesia on the incidence of DGF in recipients of kidneys of donation after circulatory death (DCD) and donation after brain death (DBD) donors

Study Overview

• Status: Completed
• Conditions: Postoperative Complications; Delayed Graft Function; Acute Rejection (AR) of Transplanted Kidney; Length of Hospital Stay; Graft Survival; Renal Outcome After Kidney Transplantation; Patient Survival; Primary Non Function
• Intervention / Treatment: Drug: propofol; Drug: sevoflurane

Detailed Description

Objective:

To compare the effect of a sevoflurane based anaesthesia versus a propofol based anaesthesia on the incidence of delayed graft function in recipients of DCD and DBD donor kidneys.

Study design:

Prospective randomized controlled European multicentre clinical trial with two parallel groups

Study population:

Patients ≥18 years scheduled for kidney transplantation with a kidney from a DBD or DCD donor

Intervention:

Patients will be included and randomised to one of the following groups:

Group 1 PROP (control): Propofol: a propofol-remifentanil based anaesthesia. Group 2 SEVO (intervention): Sevoflurane: a sevoflurane-remifentanil based anaesthesia.

Main study parameters:

Primary outcome: The two co-primary endpoints are the incidence of DGF and one-year acute rejection in recipients of DCD and DBD donor kidneys. DGF is defined as need for dialysis within the first week after transplantation, excluding one-time dialysis for hyperkalaemia. Acute rejection is defined by the modified BANFF 2013 classification and must be associated with decline in kidney function and treatment.

Secondary outcomes Functional delayed graft function (fDGF) is defined as the absence of a daily decrease of at least 10% in serum creatinine for at least three consecutive days; primary non function (PNF) defined as a permanent lack of function of the allograft; length of hospital stay and postoperative complications of all kind (28). Estimated glomerular filtration rate (eGFR) at one week and three and twelve months calculated with the CKD-EPI formula; measured GFR employing Iodinethalamate (Groningen), CrEDTA (Aarhus) and Iohexol (Oslo) at twelve months; readmissions at three and twelve months, graft survival and patient survival at twelve months.;

The investigators predefined four substudies being: Cardiac biomarkers in renal transplantation, Volatile vs Intravenous anaesthetic agent; Predictive value of urinary Biomarkers in a deceased donor kidney transplantation cohort to predict PNF, DGF, Acute rejection and long term graft function and outcome; Association between intraoperative haemodynamics and vasopressor use and graft outcome; Postoperative delirium, volatile vs Intravenous anaesthetic agent (Groningen, Aarhus);

• Study Type: Interventional
• Enrollment (Actual): 488
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark
    • Aarhus University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam University Medical Center
  • Groningen, Netherlands, 9728XR
    • University Medical Center Groningen
• Norway
  • Oslo, Norway
    • university Hospital Oslo
• Spain
  • Barcelona, Spain
    • Fundagio Puigvert

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18 years
• Written informed consent

Exclusion Criteria:

• high immunological risk as determined bij local practice
• Patients of the ABO-incompatible program

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: propofol; Group 1 PROP (control): propofol: a propofol-remifentanil based general anesthesia.	Drug: propofol; General anesthesia with propofol
Active Comparator: sevoflurane; Group 2 SEVO (intervention): Sevoflurane: a sevoflurane-remifentanil based general anesthesia.	Drug: sevoflurane; General anesthesia with sevoflurane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of delayed graft function and/or one year acute rejection	DGF is defined as need of dialysis first 7 days after transplantation Acute rejection up to 1 year after transplantation, defined by the modified BANFF 2013 classification and must be associated with decline in kidney function and treatment.	DGF: 7 days after transplantation Acute rejection: up to 1 year after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Glomerular Filtration Rate (GFR)	calculated with the CKD-EPI formula	7 days after transplantation, 3 months after transplantation, 1 year after transplantation
incidence of primary non function (PNF)	PNF is defined as permanent lack of function of the transplanted kidney. This kidney will not gain function after transplantation	up to 3 months after transplantation
Incidence of funactional Delayed Graft Function	Absence of a daily decrease of at least 10% in serum creatinine for at least three consecutive days	7 days after transplantation
Length of hospital stay	Days	From day of transplantation until the day of discharge, assessed up to 60 days
Postoperative complications of all kind		from the day of transplantation until the day of discharge, assessed up to 60 days
hospital readmissions after transplantation		3 months after transplantation and between 3 months and 1year after transplantation
Graft survival		up to 1 year after transplantation
All-cause mortality	Mortality due to any cause	up to 1 year after transplantation
measured GFR employing Iodinethalamate (Groningen), CrEDTA (Aarhus) and Iohexol (Oslo) at twelve months	In a subpopulation of Groningen, Aarhus, Oslo; employing Iodinethalamate (Groningen), CrEDTA (Aarhus) and Iohexol (Oslo)	1 year after transplantation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac biomarkers in renal transplantation, Volatile vs Intravenous anesthetic agent. A substudy of the VAPOR-2 study; a multicenter randomized controlled study	The aim of our study is to investigate cardiac biomarkers in kidney transplant recipients using two different anesthesia regimen and to investigate whether there is any difference in outcome. In this substudy we will investigate the levels and thresholds of cardiac biomarkers (Troponin-T and pro-BNP) at three time points (day 0, day 1 and day3) with two different anesthetic management (intravenous or inhalational), and the impact of outcome and MACE (major adverse cardiac events). The findings in this study may provide important information for the transplant team about which anesthesia is best suited for kidney transplant recipients with cardiovascular comorbidity.	From enrollment to 1 year follow-up
Predictive value of urinary Biomarkers in a deceased donor kidney transplantation cohort to predict PNF, DGF, Acute rejection and long term graft function and outcome	The donation and transplantation procedure is inevitably accompanied by harmful processes that impact the kidney's viability. Ischemia reperfusion injury (IRI) is one of the main harmful processes which frequently results in complications and reduced kidney function after transplantation, such as delayed graft function (DGF) or primary non-function (PNF) . It is therefore important to detect and prevent damage as a result of IRI. An improved and earlier detection of IRI-induced damage might allow therapeutic measures and improve renal function and patient outcome on a longer term. We studied several biomarkers in a living donor kidney transplantation (LDKT) cohort. We will now proceed whit analysis of the release pattern and predictive value of KIM-1, H-FABP, NAG and NGAL and novel biomarkers on short- and long-term graft outcome after deceased donor kidney transplantation	from enrollement to follow-up of 1 year
Association between intraoperative haemodynamics and graft outcome	Perioperative hemodynamic and fluid management remains one of the most debated topics in modern anesthesia, particularly in the context of kidney transplantation, where there is currently no consensus on optimal blood pressure targets. This is further complicated by the fact that the transplanted kidney is denervated, resulting in impaired autoregulation and making renal blood flow directly dependent on systemic circulation. Our objective is to identify specific intraoperative hemodynamic parameters that are associated with both short- and long-term graft outcomes. To achieve this, we will analyze continuous intraoperative hemodynamic data and assess their relationship with delayed graft function (DGF), acute rejection (AR), primary non-function (PNF), estimated glomerular filtration rate (eGFR) at 3 and 12 months, and overall graft survival.	from enrollement to 1 year follow-up
Incidence of postoperative delirium assessed by RASS in PACU and CAM on postoperative days 1-2 between volatile vs Intravenous anaesthetic agent, A substudy of the VAPOR-2 study	This substudy investigates the incidence of postoperative delirium after renal transplantation in a randomized controlled trial with two groups anesthetized using either Propofol or Sevoflurane. Postoperative delirium will be screened using RASS (Richmond agitation sedation score) in the PACU and CAM (Confusion assessment method) during the first two postoperative days on the ward. The findings from this study will provide information about the incidence of postoperative delirium following renal transplantation. Data may provide information about differences depending on the choice of anesthetic agent - Propofol versus Sevoflurane.	From day of transplantation until 2 days postoperative

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: Gertrude J Nieuwenhuijs-Moeke, MD, University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2017
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: March 23, 2016
• First Submitted That Met QC Criteria: April 1, 2016
• First Posted (Estimated): April 4, 2016

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 24, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: sevoflurane; kidney transplantation; propofol; anesthesiology
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Delayed Graft Function; Physiological Effects of Drugs; Anesthetics; Central Nervous System Depressants; Platelet Aggregation Inhibitors; Hypnotics and Sedatives; Anesthetics, Intravenous; Anesthetics, General; Anesthetics, Inhalation; Sevoflurane; Propofol
• Other Study ID Numbers: VAPOR-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon completion of the study and primary data analysis, the dataset will be anonymized and made openly accessible through a public data repository
• IPD Sharing Time Frame: Study Protocol, ICF and SAP will be shared with the protocol article which will be publihed open access Upon completion of the study and primary data analysis, the dataset will be anonymized and made openly accessible through a public data repository (start date January 2027-end date to be determined)
• IPD Sharing Access Criteria: all will be open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No