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

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

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.

Study Overview

• Status: Completed
• Conditions: Critical Illness; Hypothermia; Brain Death; Kidney Transplant; Complications; Organ Donor
• Intervention / Treatment: Procedure: Procedure control: normothermia; Procedure: Procedure active

• Study Type: Interventional
• Enrollment (Actual): 532
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Amiens, France, 80054
    • CHU Amiens-Picardie
  • Angers, France, 49000
    • CHU d'Angers
  • Angoulême, France, 16959
    • CH Angoulême
  • Avignon, France, 84000
    • Ch Avignon
  • Blois, France, 41016
    • CH de Blois
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Bourges, France, 18020
    • CH Bourges
  • Brest, France, 29200
    • CHU Brest
  • Caen, France, 14000
    • CHU caen
  • Cholet, France, 49325
    • Ch Cholet
  • Clermont-Ferrand, France
    • CHU Clermont Ferrand
  • Créteil, France, 94000
    • Hopital Henri Mondor
  • Dijon, France, 21079
    • CHU de Dijon
  • Dreux, France, 28100
    • CH de Dreux
  • Grenoble, France
    • CHU Grenoble
  • Jossigny, France, 77600
    • CH Marne la Vallée (GHEF)
  • La Roche-sur-Yon, France, 85925
    • CH La Roche sur Yon
  • La Rochelle, France, 17019
    • CH La Rochelle
  • Laval, France, 53000
    • CH Laval
  • Le Kremlin-Bicêtre, France, 94270
    • Hôpital Bicêtre
  • Le Mans, France, 72037
    • CH Le Mans
  • Lille, France, 59000
    • CHRU Lille
  • Limoges, France, 87042
    • Chu Limoges
  • Lorient, France, 56322
    • CH Lorient
  • Lyon, France
    • Chu de Lyon
  • Marseille, France, 13005
    • Hopital de la Timone
  • Marseille, France, 13005
    • Hôpital de la Conception
  • Meaux, France
    • CH de Meaux (GHEF)
  • Montpellier, France
    • CHU Montpellier
  • Morlaix, France, 29672
    • CH Morlaix
  • Nantes, France, 44093
    • Nantes University Hospital
  • Nice, France, 06000
    • CHU Nice
  • Orléans, France, 45067
    • CH Orleans
  • Paris, France, 75010
    • Hôpital Saint Louis
  • Paris, France, 75015
    • Hôpital Necker
  • Paris, France, 75013
    • Hopital de la Pitie Salpetriere
  • Paris, France, 75020
    • CHU Tenon
  • Poitiers, France, 86000
    • CHU Poitiers
  • Pringy, France, 74374
    • Ch Annecy Genevois
  • Quimper, France, 29107
    • Ch Cornouaille
  • Reims, France, 51100
    • CHU Reims
  • Rennes, France, 35000
    • Chu Rennes
  • Rouen, France, 76000
    • CHU Rouen
  • Saint Brieuc, France, 22027
    • CH Saint Brieuc
  • Saint Nazaire, France, 44606
    • CH Saint Nazaire
  • Saint-Malo, France, 35403
    • CH Saint Malo
  • Saint-Étienne, France, 42055
    • CHRU Saint-Etienne
  • Saintes, France, 17108
    • CH Saintes
  • Strasbourg, France, 67091
    • CHU Strasbourg
  • Suresnes, France, 92150
    • CHU Foch
  • Toulouse, France, 31403
    • CHU Toulouse
  • Tours, France, 37044
    • Chu Tours
  • Vandœuvre-lès-Nancy, France, 54511
    • CHRU Nancy
  • Vannes, France, 56000
    • CH Vannes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: NT normothermia; 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; 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.; Other Names: Normothermia
Experimental: HT mild hypothermia; 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; 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.; 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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Ministry of Health, France

Publications and helpful links

General Publications

• Brulé N, Canet E, Péré M, Feuillet F, Hourmant M, Asehnoune K, Rozec B, Duveau A, Dube L, Pierrot M, Humbert S, Tirot P, Boyer JM, Martin-Lefevre L, Labadie F, Robert R, Benard T, Kerforne T, Thierry A, Lesieur O, Vincent JF, Lesouhaitier M, Larmet R, Vigneau C, Goepp A, Bouju P, Quentin C, Egreteau PY, Huet O, Renault A, Le Meur Y, Venhard JC, Buchler M, Michel O, Voellmy MH, Herve F, Schnell D, Courte A, Glotz D, Amrouche L, Hazzan M, Kamar N, Moal V, Bourenne J, Le Quintrec-Donnette M, Morelon E, Boulain T, Grimbert P, Heng AE, Merville P, Garin A, Hiesse C, Fermier B, Mousson C, Guyot-Colosio C, Bouvier N, Rerolle JP, Durrbach A, Drouin S, Caillard S, Frimat L, Girerd S, Albano L, Rostaing L, Bertrand D, Hertig A, Westeel PF, Montini F, Delpierre E, Dorez D, Alamartine E, Ouisse C, Sebille V, Reignier J. Impact of targeted hypothermia in expanded-criteria organ donors on recipient kidney-graft function: study protocol for a multicentre randomised controlled trial (HYPOREME). BMJ Open. 2022 Mar 28;12(3):e052845. doi: 10.1136/bmjopen-2021-052845.

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2017
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: March 27, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease Attributes; Death; Unconsciousness; Consciousness Disorders; Body Temperature Changes; Coma; Critical Illness; Hypothermia; Brain Death
• Other Study ID Numbers: RC16_0041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No