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CompletedNCT03098706HYPOREMEUpdated Sep 14, 2026

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

An interventional study of Procedure control: normothermia and Procedure active in Organ Donor, Brain Death and Kidney Transplant; Complications, sponsored by Nantes University Hospital. Completed at 54 sites in France. Open to participants aged 50 Years and older. Per ClinicalTrials.gov, last updated 2026-09-14.

Sponsored by Nantes University Hospital · Not applicable, Interventional, and Other

Phase
Not applicable
Study type
Interventional
Enrollment
532
Allocation
Randomized
Ages
50 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Organ Donor
  • Brain Death
  • Kidney Transplant; Complications
  • Critical Illness
  • Hypothermia
03

Who can participate

Ages eligible
50 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Not applicable
Primary purpose
Other
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Outcomes assessor)
Enrollment
532 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • ProcedureProcedure 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.

    Also known as: Normothermia

  • ProcedureProcedure 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.

    Also known as: Therapeutic hypothermia/ Induce hypothermia

05

What researchers measure

Primary outcomes

  1. 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°).

    Time frame: Day 7

Secondary outcomes

  1. Temperature Profile

    comparison of temperature profile between the two arms

    Time frame: 24 hours

  2. 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.

    Time frame: 24 hours

  3. Cardiac arrest

    SParticipants will be followed for the duration of Intensive Care Unit stay and/or operating room, an expected average of 24 hours.

    Time frame: 24 hours

  4. 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.

    Time frame: 24 hours

  5. Occurrence of hypotension measured by cumulative fluid balance

    Cumulative fluid balance will be compare between 2 groups during targetted controlled temperature management period

    Time frame: 24 hours

  6. occurrence of cardiac arrest

    comparison of occurrence of cardiac arrest between the two arms

    Time frame: 24 hours

  7. Kidney function measured by serum creatinine value

    Kidney function measured by serum creatinine value

    Time frame: 24 hours

  8. 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))

    Time frame: 24 hours

  9. electrolyte balance : potassium, calcium, sodium concentration disorders in mmoL/L

    Potential hypothermia related side effects

    Time frame: 24hours

  10. glycemia in mmoL/L

    Potential hypothermia related side effects

    Time frame: 24hours

  11. liver disorder (ASAT, ALAT, GGT, PAL , BILI in UI/L )

    Potential hypothermia related side effects

    Time frame: 24hours

  12. thrombocytopenia in mm3/L

    Potential hypothermia related side effects

    Time frame: 24hours

  13. 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.

    Time frame: 24 hours

  14. Hospital mortality

    Participants will be followed for the duration of hospital stay, an expected average of 1 week.

    Time frame: Day 7

  15. Kidney function measured by serum creatinine value

    Kidney function measured by serum creatinine value at day7

    Time frame: Day 7

  16. 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))

    Time frame: Day 7

  17. Extra renal support requirement

    Extra renal support requirement at Day7

    Time frame: Day 7

  18. Kidney graft acute rejection

    Kidney graft acute rejection

    Time frame: Day 7

  19. Acute pulmonary oedema by left ventricular failure

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days.

    Time frame: Day 7

  20. 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

    Time frame: Day 7

  21. Pulmonary embolism

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  22. Acute coronary syndrome

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  23. Nosocomial Bloodstream infection

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  24. Early onset pneumonia

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  25. Central Venous Catheter infection

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  26. Urinary tract sepsis

    Participants will be followed for the duration of transplantation unit stay, an expected average of 7 days

    Time frame: Day 7

  27. Mortality at D28

    comparison of mortality at D28 between the two arms

    Time frame: D28

  28. Mortality at 3 months

    comparison of mortality at 3months between the two arms

    Time frame: 3 months

  29. Mortality at 1 year

    comparison of mortality at 1 year between the two arms

    Time frame: 1 year

  30. Length of hospital stay

    comparison of length of hospital stay between the two arms

    Time frame: 48months

  31. Kidney function measured by serum creatinine value

    Kidney function measured by serum creatinine value

    Time frame: D28

  32. 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

    Time frame: D28

  33. Extra renal support requirement defined by percentage of patients requiring at least one dialysis

    Extra renal support requirement

    Time frame: D28

  34. Kidney graft acute rejection

    Kidney graft acute rejection

    Time frame: D28

  35. Acute pulmonary oedema by left ventricular failure

    Acute pulmonary oedema by left ventricular failure

    Time frame: D28

  36. Severe arrythmia

    Severe arrythmia will be define by salvo of ventricular extrasystole, ventricular fibrillation, ventricular tachycardia, need an external shock, need anti-arrhythmic treatment.

    Time frame: D28

  37. Pulmonary embolism

    Pulmonary embolism

    Time frame: D28

  38. Acute coronary syndrome

    Acute coronary syndrome

    Time frame: D28

  39. Nosocomial Bloodstream infection

    Nosocomial Bloodstream infection

    Time frame: D28

  40. Early onset pneumonia

    Early onset pneumonia

    Time frame: D28

  41. Central Venous Catheter infection

    Central Venous Catheter infection

    Time frame: D28

  42. Urinary tract sepsis

    Urinary tract sepsis

    Time frame: D28

  43. Kidney function measured by serum creatinine value

    Kidney function measured by serum creatinine value

    Time frame: 3 months

  44. 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))

    Time frame: 3 months

  45. Extra renal support requirement defined by percentage of patients requiring at least one dialysis

    Extra renal support requirement

    Time frame: 3 months

  46. Kidney function measured by serum creatinine value

    Kidney function measured by serum creatinine value

    Time frame: 12 months

  47. 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))

    Time frame: 12 months

  48. Extra renal support requirement defined by percentage of patients requiring at least one dialysis

    Extra renal support requirement

    Time frame: 12 months

06

Study locations

54 sites
  • CHU Amiens-Picardie
    Amiens, 80054, France
  • CHU d'Angers
    Angers, 49000, France
  • CH Angouleme
    Angoulême, 16959, France
  • CH Avignon
    Avignon, 84000, France
  • CH de Blois
    Blois, 41016, France
  • CHU de Bordeaux
    Bordeaux, 33076, France
  • CH Bourges
    Bourges, 18020, France
  • CHU Brest
    Brest, 29200, France
  • CHU Caen
    Caen, 14000, France
  • Ch Cholet
    Cholet, 49325, France
  • Chu Clermont Ferrand
    Clermont-Ferrand, France
  • Hopital Henri Mondor
    Créteil, 94000, France
  • CHU de Dijon
    Dijon, 21079, France
  • CH de Dreux
    Dreux, 28100, France
  • CHU Grenoble
    Grenoble, France
  • CH Marne la Vallée (GHEF)
    Jossigny, 77600, France
  • CH La Roche sur Yon
    La Roche-sur-Yon, 85925, France
  • CH La Rochelle
    La Rochelle, 17019, France
  • CH Laval
    Laval, 53000, France
  • Hopital Bicetre
    Le Kremlin-Bicêtre, 94270, France
  • CH Le Mans
    Le Mans, 72037, France
  • CHRU Lille
    Lille, 59000, France
  • CHU Limoges
    Limoges, 87042, France
  • CH Lorient
    Lorient, 56322, France
  • CHU de Lyon
    Lyon, France
  • Hopital de la Conception
    Marseille, 13005, France
  • Hopital de la Timone
    Marseille, 13005, France
  • CH de Meaux (GHEF)
    Meaux, France
  • CHU Montpellier
    Montpellier, France
  • CH Morlaix
    Morlaix, 29672, France
  • Nantes University Hospital
    Nantes, 44093, France
  • CHU Nice
    Nice, 06000, France
  • CH Orléans
    Orléans, 45067, France
  • Hopital Saint Louis
    Paris, 75010, France
  • Hopital de la Pitié Salpetriere
    Paris, 75013, France
  • Hopital Necker
    Paris, 75015, France
  • CHU Tenon
    Paris, 75020, France
  • CHU Poitiers
    Poitiers, 86000, France
  • CH Annecy Genevois
    Pringy, 74374, France
  • CH Cornouaille
    Quimper, 29107, France
  • CHU Reims
    Reims, 51100, France
  • CHU Rennes
    Rennes, 35000, France
  • CHU Rouen
    Rouen, 76000, France
  • CH Saint Brieuc
    Saint-Brieuc, 22027, France
  • CHRU Saint-Etienne
    Saint-Etienne, 42055, France
  • CH Saint Nazaire
    Saint-Nazaire, 44606, France
  • CH Saintes
    Saintes, 17108, France
  • CH Saint Malo
    St-Malo, 35403, France
  • CHU Strasbourg
    Strasbourg, 67091, France
  • CHU Foch
    Suresnes, 92150, France
  • CHU Toulouse
    Toulouse, 31403, France
  • CHU Tours
    Tours, 37044, France
  • CHRU Nancy
    Vandœuvre-lès-Nancy, 54511, France
  • CH Vannes
    Vannes, 56000, France
07

References and documents

Publications

  • HYPOREME Trial Group. Hypothermia for expanded criteria organ donors in kidney transplantation in France (HYPOREME): a multicentre, randomised controlled trial. Lancet Respir Med. 2024 Sep;12(9):693-702. doi: 10.1016/S2213-2600(24)00117-6. Epub 2024 Jun 11. PubMed 38876137 ↗
  • Brule N, Canet E, Pere 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. PubMed 35351701 ↗
08

Registry details

Key details

Study ID
NCT03098706
Lead sponsor
Nantes University Hospital
Collaborators
Ministry of Health, France
Responsible party
Sponsor
First posted
Apr 4, 2017
Start date
Nov 8, 2017
Primary completion
Mar 21, 2022
Completion
Mar 21, 2022
Last update
Sep 14, 2026

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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