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Sepsis is responsible for 50% of all acute kidney injury (AKI) in intensive care units (ICUs), contributing greatly to multiple organ dysfunction syndrome (MODS). Special types of continuous renal replacement therapies (CRRT) have been proposed as adjuvant therapies for septic shock due to their ability to remove middle molecular weight molecules such as inflammatory mediators involved in MODS pathophysiology. These therapies are called extracorporeal " blood purification " therapies.
When CRRT is used, an anticoagulation is required to prevent clotting of the extracorporeal circuit, possibly causing bleeding in selected patients. Many anticoagulation strategies have been proposed and the most commonly used in 2013 is still unfractionated heparin. Regional citrate anticoagulation (RCA) is an interesting alternative as it dramatically decreases the bleeding risk.
The investigators hypothesize that the use of citrate with Super High Flux Continuous Veno-Venus Hemodialysis (SHF-CVVHD) would be highly beneficial over time by preserving the filter effectiveness via limiting protein adhesion (which subsequently reduces filter pore sizes (protein cake)), as compared to heparin. Consequently, higher clearances of the inflammatory mediators could be maintained over time with citrate as compared to heparin anticoagulation. In other words, for the same duration of filter use, middle molecular weight molecules and cytokines clearances would be greater with citrate as compared to heparin. To test this hypothesis, the investigators will perform a clinical randomized controlled trial which aim would be to compare middle molecular weight molecules and cytokines clearances in SHF-CVVHD using RCA versus systemic heparin anticoagulation in septic patients with AKI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RCA Group | Experimental | SHF-CVVHD with regional citrate anticoagulation |
|
| Heparin group | Experimental | SHF-CVVHD with systemic heparin anticoagulation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation) | Drug | Anticoagulation to prevent clotting of the extracorporeal circuit. Unfractionated heparin and regional citrate anticoagulation will be compared. Ci-Ca protocole for MultiFiltrate® CRRT machine :
|
| Measure | Description | Time Frame |
|---|---|---|
| Middle molecular weight molecules clearances | At each time point of the study (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h), blood and post-filter samplings will be taken in order to calculate kappa and lambda light chains of immunoglobulin clearances. | 18 months |
| Measure | Description | Time Frame |
|---|---|---|
| Clearances of cytokines and molecules of interest | At each time point of the study (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h), sampling will be simultaneously collected from blood and post-filter in order to determine cytokines (IL-1 ra, IL-10, IL-6, IL-8, β2microglobuline), urea, creatinine and albumin clearances. | T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Thomas Rimmelé, Dr | Contact | 4 72 11 02 13 | +33 | th.rimmele@gmail.com |
| Pr Bernard Allaouchiche, Pr | Contact | 4 72 11 02 13 | +33 | bernard.allaouchiche@chu-lyon.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Service de Réanimation - Pavillon P, Hôpital Edouard Herriot | Recruiting | Lyon | 69003 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33314078 | Derived | Tsujimoto H, Tsujimoto Y, Nakata Y, Fujii T, Takahashi S, Akazawa M, Kataoka Y. Pharmacological interventions for preventing clotting of extracorporeal circuits during continuous renal replacement therapy. Cochrane Database Syst Rev. 2020 Dec 14;12(12):CD012467. doi: 10.1002/14651858.CD012467.pub3. |
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|
| Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin) | Drug | Anticoagulation to prevent clotting of the extracorporeal circuit. Unfractionated heparin and regional citrate anticoagulation will be compared.
|
|
| Hemodynamic parameters | At each time point of the study (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h), clinical data and blood sampling will be collected in order to assess mean arterial pressure, heart rate, vasopressor requirement and lactate level. | T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h |
| Respiratory parameters | At each time point of the study (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h), PaO2/FIO2 ratio will be measured by blood sampling and clinical data collection. | (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h), |
| mortality | 28th day |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
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| ID | Term |
|---|---|
| D006493 | Heparin |
| ID | Term |
|---|---|
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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