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

Critical Illness Clinical Trial

— HYPOREME  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03098706
• Other study ID #: RC16_0041
• Status: Completed
• Phase: N/A
• Start date: November 8, 2017
• Est. completion date: March 21, 2022

Study information

• Verified date: June 2022
• Source: Nantes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 532
• Est. completion date: March 21, 2022
• Est. primary completion date: March 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Death
• Critical Illness
• Hypothermia
• Kidney Transplant; Complications
• Organ Donor

Intervention

Procedure:
• Procedure control: normothermia
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.
• Procedure active
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.

Locations

Country	Name	City	State
France	CHU Amiens-Picardie	Amiens
France	CHU d'Angers	Angers
France	CH Angouleme	Angoulême
France	CH Avignon	Avignon
France	CH de Blois	Blois
France	CHU de Bordeaux	Bordeaux
France	CH Bourges	Bourges
France	CHU Brest	Brest
France	CHU Caen	Caen
France	Ch Cholet	Cholet
France	Chu Clermont Ferrand	Clermont-Ferrand
France	Hopital Henri Mondor	Créteil
France	CHU de Dijon	Dijon
France	CH de Dreux	Dreux
France	CHU Grenoble	Grenoble
France	CH Marne la Vallée (GHEF)	Jossigny
France	CH La Roche sur Yon	La Roche-sur-Yon
France	CH La Rochelle	La Rochelle
France	CH Laval	Laval
France	Hopital Bicetre	Le Kremlin-Bicêtre
France	CH Le Mans	Le Mans
France	CHRU Lille	Lille
France	CHU Limoges	Limoges
France	CH Lorient	Lorient
France	CHU de Lyon	Lyon
France	Hopital de la Conception	Marseille
France	Hopital de la Timone	Marseille
France	CH de Meaux (GHEF)	Meaux
France	CHU Montpellier	Montpellier
France	CH Morlaix	Morlaix
France	Nantes University Hospital	Nantes
France	CHU Nice	Nice
France	CH Orléans	Orléans
France	CHU Tenon	Paris
France	Hopital de la Pitié Salpetriere	Paris
France	Hopital Necker	Paris
France	Hopital Saint Louis	Paris
France	CHU Poitiers	Poitiers
France	CH Annecy Genevois	Pringy
France	CH Cornouaille	Quimper
France	CHU Reims	Reims
France	CHU Rennes	Rennes
France	CHU Rouen	Rouen
France	CH Saint Brieuc	Saint Brieuc
France	CH Saint Nazaire	Saint Nazaire
France	CHRU Saint-Etienne	Saint-Étienne
France	CH Saint Malo	Saint-Malo
France	CH Saintes	Saintes
France	CHU Strasbourg	Strasbourg
France	CHU Foch	Suresnes
France	CHU Toulouse	Toulouse
France	CHU Tours	Tours
France	CHRU Nancy	Vandœuvre-lès-Nancy
France	CH Vannes	Vannes

Sponsors (2)

Lead Sponsor	Collaborator
Nantes University Hospital	Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Temperature Profile	comparison of temperature profile between the two arms	24 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	occurrence of cardiac arrest	comparison of occurrence of cardiac arrest between the two arms	24 hours
Secondary	Kidney function measured by serum creatinine value	Kidney function measured by serum creatinine value	24 hours
Secondary	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
Secondary	electrolyte balance : potassium, calcium, sodium concentration disorders in mmoL/L	Potential hypothermia related side effects	24hours
Secondary	glycemia in mmoL/L	Potential hypothermia related side effects	24hours
Secondary	liver disorder (ASAT, ALAT, GGT, PAL , BILI in UI/L )	Potential hypothermia related side effects	24hours
Secondary	thrombocytopenia in mm3/L	Potential hypothermia related side effects	24hours
Secondary	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
Secondary	Hospital mortality	Participants will be followed for the duration of hospital stay, an expected average of 1 week.	Day 7
Secondary	Kidney function measured by serum creatinine value	Kidney function measured by serum creatinine value at day7	Day 7
Secondary	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
Secondary	Extra renal support requirement	Extra renal support requirement at Day7	Day 7
Secondary	Kidney graft acute rejection	Kidney graft acute rejection	Day 7
Secondary	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
Secondary	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
Secondary	Pulmonary embolism	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Acute coronary syndrome	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Nosocomial Bloodstream infection	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Early onset pneumonia	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Central Venous Catheter infection	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Urinary tract sepsis	Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days	Day 7
Secondary	Mortality at D28	comparison of mortality at D28 between the two arms	D28
Secondary	Mortality at 3 months	comparison of mortality at 3months between the two arms	3 months
Secondary	Mortality at 1 year	comparison of mortality at 1 year between the two arms	1 year
Secondary	Length of hospital stay	comparison of length of hospital stay between the two arms	48months
Secondary	Kidney function measured by serum creatinine value	Kidney function measured by serum creatinine value	D28
Secondary	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
Secondary	Extra renal support requirement defined by percentage of patients requiring at least one dialysis	Extra renal support requirement	D28
Secondary	Kidney graft acute rejection	Kidney graft acute rejection	D28
Secondary	Acute pulmonary oedema by left ventricular failure	Acute pulmonary oedema by left ventricular failure	D28
Secondary	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
Secondary	Pulmonary embolism	Pulmonary embolism	D28
Secondary	Acute coronary syndrome	Acute coronary syndrome	D28
Secondary	Nosocomial Bloodstream infection	Nosocomial Bloodstream infection	D28
Secondary	Early onset pneumonia	Early onset pneumonia	D28
Secondary	Central Venous Catheter infection	Central Venous Catheter infection	D28
Secondary	Urinary tract sepsis	Urinary tract sepsis	D28
Secondary	Kidney function measured by serum creatinine value	Kidney function measured by serum creatinine value	3 months
Secondary	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
Secondary	Extra renal support requirement defined by percentage of patients requiring at least one dialysis	Extra renal support requirement	3 months
Secondary	Kidney function measured by serum creatinine value	Kidney function measured by serum creatinine value	12 months
Secondary	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
Secondary	Extra renal support requirement defined by percentage of patients requiring at least one dialysis	Extra renal support requirement	12 months