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Impact of the Composition of Packed Red Blood Cell Supernatant on Renal Dysfunction and Posttransfusion Immunomodulation (TRANSNEPHRON)

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ClinicalTrials.gov Identifier: NCT02763410
Recruitment Status : Recruiting
First Posted : May 5, 2016
Last Update Posted : March 28, 2017
Sponsor:
Collaborator:
Etablissement Français du Sang
Information provided by (Responsible Party):
Nantes University Hospital

Brief Summary:

Safety during transfusions is a major issue in medical economics. Despite drastic quality control measures, transfusion is still a source of short, mid and long-term morbi-mortality. This can be explained to some extent by changes in the composition of the packed red blood cell (PRBC) supernatant during storage essentially with the appearance of immunologically active compounds possibly involved in organ dysfunction on the one hand and post-transfusion immunomodulation on the other hand. These phenomena impact upon outcomes for cardiac surgery patients.

In terms of organ dysfunction, kidney failure due to acute tubular necrosis and pulmonary failure are the 2 main issues. Following cardiac surgery, 11% of patients will present with transient renal dysfunction characterised by a 25% increase in serum creatinine levels and 3.5% require dialysis. The intensity of acute renal failure (ARF) is correlated to resuscitation : a 20% increase in serum creatinine levels 2 to 3 days after surgery significantly raises morbidity rates and a 50% increase raises the mortality rate to 10%.

The precise mechanisms governing post-transfusion immunomodulation have not yet to be defined. The appearance of soluble type I Human leukocytes Antigen (HLA) molecules (sHLA-I), the FAS ligand (FAS-L) or cluster designation 40 (CD40-L) in the supernatant of PRBCs along the storage of blood products may be involved in such phenomena. These molecules are capable of activating or triggering the death of innate or adaptive immunity cells, especially the Natural Killer (NK) cells.

Consequently the investigators propose to focus specifically on the detailed composition of transfused PRBC supernatants in order to identify the candidate molecules responsible for organ dysfunction or post-transfusion immunoparalysis. The investigators will combine a clinical approach based on the transcriptional analysis of renal tubular cells in transfused patients and an ex-vivo approach investigating the effect of the supernatant on immune cells and the Natural Killer cells of healthy volunteers


Condition or disease Intervention/treatment
Renal Failure Other: PRBC transfusion

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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Impact of the Composition of the Packed Red Blood Cell Supernatant on Renal Dysfunction and Post-transfusion Immunomodulation
Actual Study Start Date : September 8, 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
control group
Patients who received between 1 and 5 PRBCs between incision and the 6th hour post-surgery, with no renal failure at the 48th hour after surgery, based on the RIFLE classification, and regardless of the transfusion received after the H6 assessment.
Other: PRBC transfusion
Renal failure group
Patients who received between 1 and 5 PRBCs between incision and the 6th hour post-surgery and who developed renal failure before H48 with no new transfusion prior to diagnosis of kidney failure.
Other: PRBC transfusion



Primary Outcome Measures :
  1. link between the composition of the PRBC supernatant and the onset of renal failure [ Time Frame: 48 hours following surgery ]

Secondary Outcome Measures :
  1. Respiratory dysfunction in the ICU defined by a blood pressure of oxygen (PaO2)/inspired oxygen fraction (FiO2) ratio < 300 on at least one occasion [ Time Frame: within 28 days ]
  2. Number of dialysis days [ Time Frame: within 28 days ]
  3. Duration of stay [ Time Frame: within 28 days ]
  4. Ventilation period (in hours); [ Time Frame: within 28 days ]
  5. ICU-acquired infection [ Time Frame: within 28 days ]
  6. Status at discharge from ICU: Dead/alive [ Time Frame: day 28 ]
  7. Study of transfusion-related accidents recorded in ICU [ Time Frame: within 28 days ]
  8. Hospital admission, regardless of cause [ Time Frame: 1 year ]
  9. Hospital admission due to infection [ Time Frame: 1 year ]
  10. Diagnosis of cancer [ Time Frame: 1 year ]
  11. Clinical course of pre-existing cancer [ Time Frame: 1 year ]
  12. Survival [ Time Frame: 1 year ]

Biospecimen Retention:   Samples With DNA
urine samples and PRBC tubing


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients:

The investigators selected cardiac surgery patients for the transfusion frequency and significant post-surgical renal morbidity.

Study centre:

The study will take place at the CHU Nantes (University Hospital Centre) where over 1500 extracorporeal circulation procedures are performed annually.

Number of patients required: 200 patients:

100 transfusion patients who have developed renal failure; 100 transfusion patients who have not developed renal failure;

Criteria

Inclusion Criteria:

  • Non-emergency cardiac surgery under extracorporeal circulation (CEC) with cardioplegia:

And no indication of pre-surgical PRBC transfusion (priming excluded), And no indication of transfusion with fresh frozen plasma or pre-surgical platelet concentrate

Exclusion Criteria:

  • Heart and/or lung transplant surgery;
  • Emergency surgery to be performed within 24 hours;
  • Patient <18 years old;
  • Pregnant woman
  • Protected adult
  • Adult incapable of expressing his/her non-opposition
  • Opposition expressed by the patient on recording his/her data;
  • No French social security;
  • Patient who underwent a transfusion in the 3 months prior to surgery;
  • Surgery due to endocarditis or suspected endocarditis;
  • Myocardial infarction < 15 days;
  • Patient receiving inotropic or vasopressor prior to surgery;
  • Patient receiving immunosuppressant treatment;
  • Patient receiving corticosteroids for 21 days or more;
  • Seropositive patient known to be suffering from HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV)
  • Currently taking antibiotics (except permitted peri-surgical antibiotic prophylaxis );
  • History of advancing cancer;
  • Clearance < 40 ml/min/m2 according to the Modification of Diet in Renal Disease (MDRD) during the pre-surgical assessment;
  • Positive irregular antibody test warranting a cross-match prior to transfusion.
  • Patients with indwelling urinary catheter preoperatively
  • preoperative positive urine culture
  • Urinary tract infection <21 days before surgery
  • Background gesture on the upper or lower urinary tract

Exclusion criteria analysis

  • In the renal insufficient group: Patient transfused plasma (s) Fresh Frozen (s) (PFCs) or concentrate (s) platelet (s) (CP) after the balance sheet T6 (6 hours after arrival in the ICU) and before the diagnosis of ARF,
  • strict anuric patient not to achieve a 50 ml urine sample at least
  • Reversal surgery requiring CEC before the 48th hour
  • Surgical Complication could explain the acute renal failure (IRA)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02763410


Contacts
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Contact: Roquilly Antoine, PH 02 40 08 30 08 antoine.roquilly@gmail.com
Contact: Vourch Mickael, PH 02 40 08 30 08 vourchm@gmail.com

Locations
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France
CHU de Nantes Recruiting
France, Nantes, France, 44093
Contact: Roquilly Antoine, PH    02 40 08 30 08    antoine.roquilly@chu-nantes.fr   
Contact: Vourc'h Mickael, PH    02 40 08 30 08    vourchm@gmail.com   
Sponsors and Collaborators
Nantes University Hospital
Etablissement Français du Sang

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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT02763410     History of Changes
Other Study ID Numbers: RC15_0420
First Posted: May 5, 2016    Key Record Dates
Last Update Posted: March 28, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases