Renal Transplantation and Inhaled Anesthetic Sevoflurane (SEVOREIN)

Phase 3

Completed

• Conditions: End-stage Chronic Renal Disease; Severe Acute Kidney Failure; Renal Transplantation
• Interventions: Drug: Propofol; Drug: Sevoflurane

• Registration Number: NCT00337051
• Lead Sponsor: University Hospital, Bordeaux

Brief Summary

Renal transplantation is characterized by ischemia-reperfusion lesions in allograft. In a previous study, Julier and al. (Anesthesiology 2003) have demonstrated that sevoflurane reduces glomerular lesions in kidney of patients undergoing a cardiovascular surgery and présenting with ischemia-reperfusion phenomena.

The purpose of the study is to evaluate the effects of sevoflurane on the recovery of renal graft function in patients after kidney transplantation.

This study will be a randomized, double blinded, controlled clinical trial and 120 patients undergoing renal allograft transplantation will be included.

Patients will be divided into 2 groups: one group of patients who will receive sevoflurane (evaluated treatment) for anaesthesia and the other one who will receive propofol (reference treatment).

We will evaluate renal function for one year after transplantation. Ours results will confirm or not that sevoflurane protects kidney function from ischemia-reperfusion lesions.

Detailed Description

Introduction :

Renal transplantation is characterized by ischemia-reperfusion lesions in allografts. Prolonged cold ischemia duration, age of donor (older than 50) or donor cardiac arrest are common factors associated with delayed graft function. In cardiac surgery, Sevoflurane (a volatile-inhaled anesthetic) protects the heart from ischemia-reperfusion lesions and preserves glomerular filtration function in patients. This cardioprotective effect involves K+-ATP mitochondrial channels which are also known to be expressed in renal cells.

Therefore, it is interesting to evaluate Sevoflurane effects in the context of renal allograft transplantation in order to shorten the delayed graft function and enhance post-operative renal function

Objectives:

Main goal:

Evaluate time necessary to obtain serum creatinine levels inferior to 200µmol/l of the recipient in the group receiving Sevoflurane in comparison with the group of patients receiving propofol infusion for general anaesthesia

Secondary goals:

* Compare serum creatinine levels in the two groups at day14

* Compare patient survival and acute rejection occurrence over a period of one-year follow-up in the two groups

* Compare the safety of both anesthetics assessed as renal tubular injury-toxicity (by measuring serum levels of NAG) and levels of serum inorganic fluor products in the post-operative period; and by referencing all adverse events

* Compare the effect of both anesthetics on delayed-recovery graft function by assessing clinical end-points (daily diuresis, number of haemodialysis sessions in the two weeks following transplantation) and biological end-points (serum creatinin and cystatinC levels in the two weeks following transplantation)

Patients:

120 patients scheduled to undergo a renal allograft transplantation with transplants defined by either a cold ischemia duration of more than 20h or a donor's age older than 50 years or a donor cardiac arrest will be randomized in 2 groups of sixty patients undergoing two different general anesthesia protocols. All patients will be included in the Renal Transplantation Unit of Bordeaux University Hospital, Aquitaine, France.

Methods:

This study will be a clinical randomized trial on 2 parallel groups. It will be double-blind for nephrologists and biologists who evaluate the end-points and will involve a population of renal transplanted patients.

The study will compare clinical and biological outcomes according to the type of general anesthesia undergone for transplantation:

* One group of patients with inhaled anesthesia by Sevoflurane (evaluated treatment)

* One group of patients with intravenous anesthesia by propofol (reference treatment).

Patients will be evaluated over a period of one year follow-up. This study is multicentric, based in Aquitaine for a period of three years, involving anaesthesiologists, nephrologists, and urologists.

Baseline brain-dead donor and graft donation characteristics will be collected by the Hospital Coordination team in Bordeaux, Pau and Bayonne.

Statistical analysis will be on intention-to-treat basis. Expected results: 1-Demonstrate Sevoflurane benefit for ischemia-reperfusion protection in renal allograft and a shortened recovery of renal graft function in the two-week post-operative period in the group allocated for Sevoflurane exposure during anaesthesia. 2-Confirm the good safety of Sevoflurane exposure in chronic end-stage renal diseased patients undergoing renal transplantation.

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2006-06-14
• Study First Submitted QC: 2006-06-14
• Study First Posted: 2006-06-15
• Primary Completion: 2010-02
• Status Verified: 2010-06
• Study Completion: 2010-06
• Last Update Submitted: 2010-06-22
• Last Update Posted: 2010-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• age > 18 years
• scheduled to undergo renal allograft transplantation
• transplant : cold ischemia duration > 20 hours or donor age > 50 years or donor cardiac arrest
• ASA 2-3
• social security affiliation
• informed consent signed

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Exclusion Criteria

• halogenated anesthetic agent hypersensibility
• medical history or familial history of malignant hyperthermia
• porphyria
• pregnancy or breast feeding
• hyperimmunized patient
• participation in an immunosuppressive drug trial

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
P	Propofol	General Anesthesia With Propofol TCI
S	Sevoflurane	General Anesthesia with sevoflurane (inhalation) as hypnotic

Primary Outcome Measures

Name	Time	Method
time to obtain serum creatinine levels inferior to 200µmol/l in the transplant recipient	evalued at 14 days

Secondary Outcome Measures

Name	Time	Method
creatinemia levels at day 14	evalued at 14 days
patient survival	during 1 year follow-up
acute rejection occurrence	during 1 year follow-up
safety : renal tubular injury toxicity (serum cystatinC and NAG), serum inorganic fluor products	1, 2 and 3 days after kidney transplantation
other clinical end-points: daily diuresis, number of haemodialysis sessions	during the two weeks following transplantation
other biological end-points: serum creatinin and cystatinC levels	during the two weeks following transplantation
Other adverse events	during one year folow-up

Trial Locations

Locations (1)

Département d'anesthésie réanimation 1 - Hôpital Pellegrin - CHU de Bordeaux; 🇫🇷 Bordeaux, France