Therapeutic Hypothermia in Expanded Criteria Brain-dead Donors and Kidney-graft Function

Study Overview
=================
Brief Summary
-----------------
Each year, only one third of patients registered on the waiting list receive a kidney transplant. Numerous paths are being explored with the aim of reversing this shortage. The first is to increase the number of organs by developing harvesting from donors in a state of brain-death (BD) termed expanded criteria donors or from patients deceased from circulatory arrest. Another fundamental factor is to insure the success of the transplant by limiting the dysfunction of donor kidneys, marked by a delayed graft function (DFG). The development of techniques to insure correct perfusion of harvested organs, and the optimization of reanimation and intensive care of brain-dead donors constitute important factors in DGF reduction. Therapeutic Hypothermia could to be an attractive care strategy for BD patients.

Official Title
-----------------
Impact of Therapeutic Hypothermia in Expanded Criteria Brain-dead Donors on Kidney-graft Function in the Kidney-transplant Recipients: Multicenter Randomized Controlled Trial HYPOREME

Conditions
-----------------
Organ Donor, Brain Death, Kidney Transplant; Complications, Critical Illness, Hypothermia

Intervention / Treatment
-----------------
* Procedure: Procedure control: normothermia
* Procedure: Procedure active


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: For donors: legal determination of death by neurologic criteria/deceased organ donor/no medical contre-indication to donation/Information given to the authorizing surrogate/ Pregnant women. For transplant recipients : age 18 years or greater /information given and no opposition signed by recipients. Exclusion Criteria: For donors: no legal determination of death by neurologic criteria/not a deceased organ donor/ medical contre-indication to donation/ no Information given to the authorizing surrogate. For transplant recipients: age <18 years / no information given and/or opposition signed by recipients.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

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

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

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

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: NT normothermia<br>After information for donation and research has been explained, organ donors in the normothermia (NT) group will either be maintained to spontaneously reach a body temperature of 36,5 °C-37,5°, until transfer to the operating room. | Procedure: Procedure control: normothermia<br>* Temperature will be maintained between 36.5° and 37.5°C in the control group. In case of temperature superior to 37.5°C or inferior to 36.5°C, a pharmaceutical treatment and/or active cooling or warming will be introduce to maintain temperature between the range of 36.5 - 37.5°C.<br>* Other names: Normothermia;|
| Experimental: HT mild hypothermia<br>The intervention will take place after information for donation and research has been explained . Organ donors in the intervention group will either be actively warmed or allowed to reach a body temperature of 34 °C-35°C, until transfer to the operating room. | Procedure: Procedure active<br>* Therapeutic hypothermia ie targeted controlled temperature between 34° and 35°C will be induced in the active group. Usual method of controlled temperature will be used in ICU: internal active method or external active method.<br>* Other names: Therapeutic hypothermia/ Induce hypothermia;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rate of patients with delayed graft function (DGF) | DGF is the recipient's requirement for dialysis during the first week after transplantation. To show the interest of Targeted Temperature Management in order to optimize the functional recovery of transplanted kidney transplants by comparing 2 groups of recipient subjects: those receiving one Graft from an expanded criteria donors maintained in hypothermia (34°-35°) and those receiving a graft from an expanded criteria donors maintained in normothermia (36,5°-37,5°). | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temperature Profile | comparison of temperature profile between the two arms | 24 hours | 
| Severe arrhythmias | Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment. Participants will be followed for the duration of Intensive Care Unit stay and/or operating room, an expected average of 24 hours. | 24 hours | 
| Cardiac arrest | SParticipants will be followed for the duration of Intensive Care Unit stay and/or operating room, an expected average of 24 hours. | 24 hours | 
| Occurrence of hypotension measured by Total dose of inotropic drugs | Total dose of different inotropic drugs (Epinephrine, Norepinephrine, Dobutamine) will be compare between 2 groups during targetted controlled temperature management period. | 24 hours | 
| Occurrence of hypotension measured by cumulative fluid balance | Cumulative fluid balance will be compare between 2 groups during targetted controlled temperature management period | 24 hours | 
| occurrence of cardiac arrest | comparison of occurrence of cardiac arrest between the two arms | 24 hours | 
| Kidney function measured by serum creatinine value | Kidney function measured by serum creatinine value | 24 hours | 
| Kidney function measured by CKD EPI score | Kidney function measured by CKD EPI score (= 141 x min(Scr/K,1)a x max(Scr/K,1)-1,209 x 0,993Age x 1,018 (for women)) | 24 hours | 
| electrolyte balance : potassium, calcium, sodium concentration disorders in mmoL/L | Potential hypothermia related side effects | 24hours | 
| glycemia in mmoL/L | Potential hypothermia related side effects | 24hours | 
| liver disorder (ASAT, ALAT, GGT, PAL , BILI in UI/L ) | Potential hypothermia related side effects | 24hours | 
| thrombocytopenia in mm3/L | Potential hypothermia related side effects | 24hours | 
| Number of individual organs transplanted | Participants will be followed for the duration of Intensive care unit length of stay, and operating room, an average of 24 hours. | 24 hours | 
| Hospital mortality | Participants will be followed for the duration of hospital stay, an expected average of 1 week. | Day 7 | 
| Kidney function measured by serum creatinine value | Kidney function measured by serum creatinine value at day7 | Day 7 | 
| Kidney function measured by CKD EPI | Kidney function measured by CKD EPI (= 141 x min(Scr/K,1)a x max(Scr/K,1)-1,209 x 0,993Age x 1,018 (for women)) | Day 7 | 
| Extra renal support requirement | Extra renal support requirement at Day7 | Day 7 | 
| Kidney graft acute rejection | Kidney graft acute rejection | Day 7 | 
| Acute pulmonary oedema by left ventricular failure | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days. | Day 7 | 
| Severe arrythmia | Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment. Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Pulmonary embolism | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Acute coronary syndrome | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Nosocomial Bloodstream infection | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Early onset pneumonia | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Central Venous Catheter infection | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Urinary tract sepsis | Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days | Day 7 | 
| Mortality at D28 | comparison of mortality at D28 between the two arms | D28 | 
| Mortality at 3 months | comparison of mortality at 3months between the two arms | 3 months | 
| Mortality at 1 year | comparison of mortality at 1 year between the two arms | 1 year | 
| Length of hospital stay | comparison of length of hospital stay between the two arms | 48months | 
| Kidney function measured by serum creatinine value | Kidney function measured by serum creatinine value | D28 | 
| Kidney function measured by CKD EPI | Kidney function measured by CKD EPI (= 141 x min(Scr/K,1)a x max(Scr/K,1)-1,209 x 0,993Age x 1,018 (for women)) at Day28 | D28 | 
| Extra renal support requirement defined by percentage of patients requiring at least one dialysis | Extra renal support requirement | D28 | 
| Kidney graft acute rejection | Kidney graft acute rejection | D28 | 
| Acute pulmonary oedema by left ventricular failure | Acute pulmonary oedema by left ventricular failure | D28 | 
| Severe arrythmia | Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment. | D28 | 
| Pulmonary embolism | Pulmonary embolism | D28 | 
| Acute coronary syndrome | Acute coronary syndrome | D28 | 
| Nosocomial Bloodstream infection | Nosocomial Bloodstream infection | D28 | 
| Early onset pneumonia | Early onset pneumonia | D28 | 
| Central Venous Catheter infection | Central Venous Catheter infection | D28 | 
| Urinary tract sepsis | Urinary tract sepsis | D28 | 
| Kidney function measured by serum creatinine value | Kidney function measured by serum creatinine value | 3 months | 
| Kidney function measured by CKD EPI | Kidney function measured by CKD EPI (= 141 x min(Scr/K,1)a x max(Scr/K,1)-1,209 x 0,993Age x 1,018 (for women)) | 3 months | 
| Extra renal support requirement defined by percentage of patients requiring at least one dialysis | Extra renal support requirement | 3 months | 
| Kidney function measured by serum creatinine value | Kidney function measured by serum creatinine value | 12 months | 
| Kidney function measured by CKD EPI | Kidney function measured by CKD EPI (= 141 x min(Scr/K,1)a x max(Scr/K,1)-1,209 x 0,993Age x 1,018 (for women)) | 12 months | 
| Extra renal support requirement defined by percentage of patients requiring at least one dialysis | Extra renal support requirement | 12 months |