Septic ShockRCA-SHANCT01839578
Citrate Versus Heparin Anticoagulation: Effect on Molecules Clearances
A study testing Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation) and Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin) in people with Septic Shock, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation) and Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- May 2013to Apr 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female critically ill patients over the age of 18 years old
- Acute Kidney Injury requiring CRRT defined using the Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification with criterion I or worse.
- Septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.
- Written informed consent obtained from the patient or a patient's legal representative
- Patient patient's legal representative able to agree to patient's enrollment in the study with informed consent.
Who cannot join
- Pregnancy
- Participation in another research study protocol
- Known heparin induced thrombopenia or contraindication to heparin
- Pre-existing chronic renal failure on chronic dialysis
- Therapeutic anticoagulation with heparin for another reason (e.g. chonic arrhythmia)
- Severe liver failure (15% prothrombin time)
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Service de Réanimation - Pavillon P, Hôpital Edouard Herriot
Lyon, 69003
Thomas Rimmelé, Dr, 4 72 11 02 13 ext. +33, th.rimmele@gmail.com
Bernard Allaouchiche, Pr, 4 72 11 02 13 ext. +33, bernard.allaouchiche@chu-lyon.fr
About this study
Official title: Regional Citrate Versus Systemic Heparin Anticoagulation for Super High-flux Continuous Hemodialysis in Septic Shock: Effect on Middle Molecular Weight Molecules Clearances
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.
- Conditions
- Septic Shock
- Being tested
- Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation), Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin)
- Keywords
- cytokines, blood purification, super high flux hemodialysis
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 :
- 4% trisodium citrate solution
- Calcium chloride solution (100 mmol/L)
- Dialysate flow rate: 35 ml/kg/h
- Blood flow rate: adjusted to maintain a ratio blood flow rate / dialysate flow rate of 3
- Citrate infusion titrated to maintain postfilter ionized calcium between 0.25 and 0.35 mmol/L.
- Calcium chloride infusion titrated to maintain systemic ionized calcium between 1.12 and 1.2 mmol/L.
- Blood flow adapted to the acid-base status
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.
- Continuous infusion of unfractionated heparin: starting infusion rate at 600 IU/h then adjusted to maintain partial thromboplastin time at 1-1.4 times the normal value.
- Standard dialysate for CRRT : Prismasol® K2 solution
- Dialysate flow rate: 35 ml/kg/h
- Blood flow rate: adjusted to maintain a ratio blood flow rate / dialysate flow rate of
| Study group | Role | What they receive |
|---|---|---|
| RCA Group | Experimental | SHF-CVVHD with regional citrate anticoagulation Receives: Drug: Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation) |
| Heparin group | Experimental | SHF-CVVHD with systemic heparin anticoagulation Receives: Drug: Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 18 months
Secondary outcomes (4)
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.
Measured: T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h
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.
Measured: 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.
Measured: (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h),
mortality
Measured: 28th day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2013 (estimated)
- Study startMay 2013
- Primary completionNov 2014 (estimated)
- Study completionApr 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01839578
- Sponsor's protocol ID
- 2012.724
- Acronym
- RCA-SHA
- Status last verified
- Aug 2014
- First submitted
- 22 Apr 2013
- Last updated
- 27 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 33314078
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regional Citrate Versus Systemic Heparin Anticoagulation for Super High-flux Continuous Hemodialysis in Septic Shock: Effect on Middle Molecular Weight Molecules Clearances
- ClinicalTrials.gov ID
- NCT01839578
- Acronym / sponsor ID
- RCA-SHA / 2012.724
- Conditions
- Septic Shock
- Keywords
- cytokines, blood purification, super high flux hemodialysis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- May 2013
- Primary completion
- Nov 2014 (estimated)
- Study completion
- Apr 2015 (estimated)
- First posted
- 25 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RCA Group | Experimental | Drug: Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation)SHF-CVVHD with regional citrate anticoagulation |
| Heparin group | Experimental | Drug: Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin)SHF-CVVHD with systemic heparin anticoagulation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female critically ill patients over the age of 18 years old
- Acute Kidney Injury requiring CRRT defined using the Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE) classification with criterion I or worse.
- Septic shock as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference.
- Written informed consent obtained from the patient or a patient's legal representative
- Patient patient's legal representative able to agree to patient's enrollment in the study with informed consent.
Key exclusion criteria (6 listed)
- Pregnancy
- Participation in another research study protocol
- Known heparin induced thrombopenia or contraindication to heparin
- Pre-existing chronic renal failure on chronic dialysis
- Therapeutic anticoagulation with heparin for another reason (e.g. chonic arrhythmia)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation)Anticoagulation to prevent clotting of the extracorporeal circuit. Unfractionated heparin and regional citrate anticoagulation will be compared. Ci-Ca protocole for MultiFiltrate® CRRT machine : * 4% trisodium citrate solution * Calcium chloride solution (100 mmol/L) * Dialysate flow rate: 35 ml/kg/h * Blood flow rate: adjusted to maintain a ratio blood flow rate / dialysate flow rate of 3 * Citrate infusion titrated to maintain postfilter ionized calcium between 0.25 and 0.35 mmol/L. * Calcium chloride infusion titrated to maintain systemic ionized calcium between 1.12 and 1.2 mmol/L. * Blood flow adapted to the acid-base status | Drug | RCA Group |
| Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin)Anticoagulation to prevent clotting of the extracorporeal circuit. Unfractionated heparin and regional citrate anticoagulation will be compared. * Continuous infusion of unfractionated heparin: starting infusion rate at 600 IU/h then adjusted to maintain partial thromboplastin time at 1-1.4 times the normal value. * Standard dialysate for CRRT : Prismasol® K2 solution * Dialysate flow rate: 35 ml/kg/h * Blood flow rate: adjusted to maintain a ratio blood flow rate / dialysate flow rate of | Drug | Heparin group |
Primary outcome
Middle molecular weight molecules clearances
Time frame: 18 months
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.
4 secondary outcomes
Clearances of cytokines and molecules of interest
Time frame: T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h
Hemodynamic parameters
Time frame: T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h
Respiratory parameters
Time frame: (T=1h,T=4h,T=12h,T=24h, T=48h, and T=72h),
mortality
Time frame: 28th day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2014.
- Derived from this study: PubMed 33314078Tsujimoto 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Anticoagulation to prevent clotting of the extracorporeal circuit. (regional citrate anticoagulation) and Anticoagulation to prevent clotting of the extracorporeal circuit (Unfractionated heparin) in people with Septic Shock, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Thomas Rimmelé, Dr (4 72 11 02 13 ext. +33, th.rimmele@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Middle molecular weight molecules clearances (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01839578, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2014.