EPI-STORM: Cytokine Storm in Organ Donors

NCT03786991 | Recruiting

• 1 other identifier: MP-31-2019-2960
• Study Type: observational
• Target: 105
• Locations: 1 country
• Sites: 4

Brief Summary

Kidney and liver transplantation are the treatment of choice and are often the last therapeutic option offered to patients with chronic renal and liver failure. More than 70% of kidneys and liver available for transplantation are obtained from donors following neurological death. Unfortunately, compared to living donation, transplant function, graft survival, and recipient survival are consistently inferior with kidneys and liver from neurologically deceased donors. This difference lies with the exacerbated pro-inflammatory state characteristic of deceased donors. Indeed, when neurologic death occurs, the immune system releases substances in the blood that could harm organs and particularly the liver and the kidneys. We believe that achieving a better understanding of the inflammatory processes of organ donors could be greatly informative to design future randomized controlled trial assessing the effect of personalized immunosuppressive therapy on organ donors to ultimately improve the care provided to donors so as to increase the number of organs available for transplantation and enhancing the survival of received grafts

Conditions

Organ Donation; Liver Transplantation; Kidney Transplantation; Graft Dysfunction

Outcome Measures

Primary Outcomes (1)

• Kidney delayed graft function

  Requirement for renal replacement therapy within the first 7 days following transplantation or decrease of \< 10% of creatinine after 3 days after transplantation, or creatinine \> 250 µmol/l at day 5 with evidence of delayed graft function by renal scintigraphy

  7-days post-transplantation

Secondary Outcomes (5)

• Liver early graft dysfunction

  7-days post-transplantation

• Quantification of circulatory cytokines

  From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 25 donors).

• Identification of inflammatory-related miRNA targets using micro-transcriptome analyses

  From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room) ;25 donors).

• Validation of inflammatory-related miRNA targets using targeted quantification

  From ICU admission up to organ recovery (5 timepoints(1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).

• Validation of circulatory cytokines

  From ICU admission up to organ recovery (5 timepoints (1:ICU admission; 2: consent to organ donation, 3: 4 to 8 hours after sample #2, 4: 24 hours after sample #2; 5: prior to transfer from ICU to operating room); 105 donors).

Study Arms (2)

Organ donors

Organ donors after neurologic death (NDD) of 18 years old and older for whom consent to organ donation has been obtained.

Other: No intervention

Liver and kidney Recipients

Liver and kidney recipients of 18 years old and older.

Other: No intervention

Interventions

No intervention OTHER

No intervention

Liver and kidney Recipients; Organ donors

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Organ donors by neurologic death and liver and kidney recipients

You may qualify if:

• Patient admitted to the intensive care unit with a serious neurologic lesion
• Glasgow Coma Scale score ≤ 4
• Absence of sedation for the last 6 hours
• Age ≥ 18 years old

You may not qualify if:

• S. aureus bacteremia
• Active neoplasia
• Receiving immunosuppressive therapy (including steroids) for \> 3 months
• Specific to potential liver donors:
• Hepatic insufficiency defined as i) INR \> 1.5, ii) hepatic encephalopathy, iii) AST, ALT \> 2 times normal value
• Specific to potential kidney donors:
• Polycystic kidney disease
• Chronic renal failure (i.e., eGFR \< 60 ml/min)
• Phase 2 of the study:
• Organ donor after neurologic death (DND) declaration as determined by the attending physician
• Consent to organ donation obtained

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Centre de recherche du CHUS: collaborator

Study Sites (4)

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Centre Hospitalier Universitaire de Montréal

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

Centre Hospitalier Universitaire de Québec- Université Laval

Québec, Quebec, G1V 4G2, Canada

RECRUITING

CIUSSS de l'Estrie-CHUS

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Related Publications (1)

• Clement AA, Lamarche D, Masse MH, Legare C, Tai LH, Fleury Deland L, Battista MC, Bouchard L, D'Aragon F. Time-course full profiling of circulating miRNAs in neurologically deceased organ donors: a proof of concept study to understand the onset of the cytokine storm. Epigenetics. 2022 Nov;17(11):1546-1561. doi: 10.1080/15592294.2022.2076048. Epub 2022 May 21.

  PMID: 35603508 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (including miRNA and buffy coat) will be drawn at 5 specific time points: following ICU admission when patient has a serious neurological lesion, as soon as possible after consent to organ donation, as well as 4 to 8 hours and 24 hours after the first sample of phase 2 has been drawn. A final draw will be made prior to transfer from the ICU to operating room for organ recovery. A substudy will be conducted in some centers and we will collect samples at time of aortic cross clamp during surgery

Study Officials

• Dr Frédérick D'Aragon, MD FRCPC MSc

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Hélène Masse, RRT, M.Sc.

CONTACT

819-346-1110; marie-helene.masse3@usherbrooke.ca

Daphnée Lamarche, PhD

CONTACT

819-821-8000; daphnee.lamarche@usherbrooke.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 26, 2018
• Study Start: December 16, 2018
• Primary Completion: March 24, 2025
• Study Completion: December 1, 2025
• Last Updated: April 2, 2025

Record last verified: 2024-05

Locations

CA (4)