PaNeX: Partial Nephrectomy Under Xenon

Study Overview
=================
Brief Summary
-----------------
Purpose of this study is to determine whether Xenon - as compared to Isoflurane - shows a nephroprotection after partial nephrectomy.

Detailed Description
-----------------
A partial nephrectomy is accompanied by ischemia time, followed by reperfusion. This frequently leads to a kidney injury of the remained tissue and decrease of the renal function after surgery. As it was shown that Xenon has protective properties against ischemia/reperfusion injury, the investigators hypothesize that Xenon application during partial nephrectomy leads to a stronger nephroprotection than an anesthesia with Isoflurane. The study will be conducted by two investigator types: The study enrollment and the post-anesthesia follow-up will be performed by Investigator I who is blinded to the study treatment. Investigator II will only perform general anesthesia for partial nephrectomy and will therefore necessarily be unblinded to the treatment conditions. Patients will be randomly assigned to one of the following study groups. Group 1 (Xenon) will receive Xenon for maintenance of balanced anesthesia for partial nephrectomy. Group 2 (Isoflurane) will receive Isoflurane for the same surgery.

Official Title
-----------------
Impact of Xenon-anesthesia on the Renal Function After Partial Nephrectomy - PaNeX: Partial Nephrectomy Under Xenon:a Pilot Study

Conditions
-----------------
Renal Function After Partial Nephrectomy

Intervention / Treatment
-----------------
* Drug: Xenon
* Drug: Isoflurane


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients willing and able to complete the requirements of this study Patients with renal carcinoma restricted to one kidney Patients undergoing partial nephrectomy Men and women >= 18 yrs Informed consent Exclusion Criteria: Chronic renal failure with a GFR < 60ml/min/1,73m2 body surface area American Society of Anesthesiologists (ASA)>III Hypersensitivity to the study anaesthetics Chronic obstructive pulmonary disease (COPD) GOLD IV Acute coronary syndrome during the last 24 hours; haemodynamic instability, requirement of inotropic support Severe cardial dysfunction New York Heart Association (NYHA) >III Disabling neuropsychiatric disorders Increased intracranial pressure pregnant or breastfeeding women Women of childbearing potential Presumed uncooperativeness or legal incapacity Lack of informed consent Participation in a concomitant trial within the last 30 days

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xenon<br>Gaseous anesthetic, dosage: 60% (v/v) in 40% oxygen, continuous application during surgery | Drug: Xenon<br>* general anaesthesia with xenon 60% in oxygen (FiO2=0.4)<br>* Other names: Lenoxe;|
| Active Comparator: Isoflurane<br>Inhalative anesthetic, dosage: 1.2% (v/v) in 40% oxygen/medical air , continuous application during surgery | Drug: Isoflurane<br>* general anesthesia with isoflurane 1.2% in 40% oxygen/medical air<br>* Other names: Forene;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the impact of xenon-anesthesia on the renal function after partial nephrectomy, compared to an isoflurane-anesthesia. | Evaluation of the maximum decrease of glomerular filtration rate (GFR) within 7 days after partial nephrectomy surgery. Maximum decrease will be assessed by the difference between the baseline value of GFR and the minimum value of GFR after surgery. | Within the first 7 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Ischaemia time | Intraoperatively | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Duration of xenon/isoflurane exposition before and after the kidney ischemia time. | Intraoperatively | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Tumor size and histology, if applicable detection of hypoxia-inducible factor 1α (HIF-1α) in healthy resection border tissue | Intraoperatively until discharge from hospital | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Measurement of macrophage migration inhibitory factor (MIF) in serum | Intraoperatively and within the first 7 postoperative days | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Course of GFR determined with the Cystatin C value in serum | preaoperativ and Within the first 7 postoperative days | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Course of creatinine value in serum | preaoperativ and Within the first 7 postoperative days | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Urine output within the first 48houres after surgery | Within the first 7 postoperative days | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | If applicable determination of kidney injury molecule-1 (KIM-1)or neutrophil gelatinase-associated lipocalin (NGAL) | Within the first 7 postoperative days | 
| Secondary efficacy criteria for using xenon-anaesthesia during partial nephrectomy. | Determination of acute kidney failure according to the AKIN classification | Within the first 7 postoperative days | 
| Safety criteria for using xenon-anaesthesia during partial nephrectomy. | Doses and concentration of study treatments | intraoperative | 
| Safety criteria for using xenon-anaesthesia during partial nephrectomy. | The peri-anaesthetic respiratory profile | intraoperative and within the first 7 postoperative days | 
| Safety criteria for using xenon-anaesthesia during partial nephrectomy. | The peri-anaesthetic haemodynamic profile | intraoperative and within the first 7 postoperative days | 
| Safety criteria for using xenon-anaesthesia during partial nephrectomy. | Intra-operative blood loss | intraoperative | 
| Safety criteria for using xenon-anaesthesia during partial nephrectomy. | The incidence of adverse event (AE) and serious adverse event (SAE) | intraoperative and within the first 7 postoperative days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Xenon, Isoflurane, Anesthetics, Inhalation, Nephroprotection, Partial nephrectomy, Xenon versus Isoflurane anesthesia