Acute Kidney InjuryNCT05796661
Patients Undergoing Continuous Venovenous Hemodiafiltration: Effects of Increased Blood Flow
A study testing Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration in people with Acute Kidney Injury, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
Trial summary
Acute Kidney Injure (AKI) is a syndrome with high incidence and prevalence in Intensive Care Units (ICU). It is estimated that 50% of the in the sector present AKI at some point and 10 to 15% require renal replacement therapy (RRT). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteBrazil
- Study dates
- 9 Jan 2023to 30 Sep 2024
- 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
None listed.
Who cannot join
- Age < 18 years.
- Weight < 50 Kg.
- Refusal to participate in the study (absence of informed consent).
- Patient with chronic kidney disease on dialysis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of Filters Useful Life, Metabolic Control, Electrolyte Profile and Acid-base Balance During Regional Anticoagulation With 4% Trisodium Citrate in Patients Undergoing CVVHDF: Effects of Increased Blood Flow
Acute Kidney Injure (AKI) is a syndrome with high incidence and prevalence in Intensive Care Units (ICU). It is estimated that 50% of the in the sector present AKI at some point and 10 to 15% require renal replacement therapy (RRT). Although studies do not show the superiority of continuous methods, the most severely ill patients are directed to this type of RRT. A disadvantage of continuous therapies is the need for anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture).
On the one hand, ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter clotting. There is no consensus on what would be the optimal blood flow (Qb) in continuous dialysis, especially when regional citrate anticoagulation (RCA) is used. Theoretically, a higher flow rate would prevent stasis in the system and decrease the risk of filter clotting. Studies show conflicting results. Increasing Qb from 150 to 250 mL/min showed that circuit life and the chance of coagulation were similar. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow. Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter. Therefore, the higher the convection rate, the higher the blood flow should be to keep the FF in the optimal range. Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing the blood flow, the citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could cause its overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when its maximum metabolizing capacity is not reached and there is an excess of citrate infusion relative to the buffering requirement. Thus, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients undergoing continuous venovenous hemodiafiltration (CVVHDF), regional citrate anticoagulation during blood flow augmentation.
Read the detailed description
Acute kidney injury (AKI) is a clinical syndrome with a high incidence and prevalence in Intensive care units (ICU). It is estimated that 50% of ICU patients have AKI at some point.
About 10-15% of these individuals require renal replacement therapy (RRT). Although studies have not conclusively shown the superiority of continuous methods, the most severe patients are usually referred for this type of therapy.
The main indications for continuous therapies are hemodynamic instability, cardiogenic shock, severe respiratory insufficiency, risk situations for brain edema, hypercatabolism, need for strict volume control, acute liver disease and major sodium disturbances. One of the main disadvantages of continuous therapies is the necessity of anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture). On the one hand, the lack or ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter coagulation. On the other hand, excessive use of anticoagulants, especially heparin, is associated with bleeding and increased transfusions.
In this scenario, regional anticoagulation with citrate (RCA) has become the method of choice in the different modalities of continuous dialysis. When compared to heparin, the use of regional citrate anticoagulation is associated with less bleeding and transfusion need and longer life of the extracorporeal system. It also seems to decrease endothelial activation, neutrophil degranulation and activation of the complement system.
The anticoagulate property of citrate is based on its binding to calcium (Ca). Citrate quenches Ca in the extracorporeal system, an essential cofactor in several steps of coagulation. Optimal anticoagulation is achieved when ionic Ca concentration in the extracorporeal circuit is maintained between 0.25 and 0.35 mmol/L. This is usually achieved with a citrate level in the circuit around 4mmol/L of blood. Depending on the modality chosen and other factors, up to 60% of the citrate-Ca complex is eliminated during passage through the filter (molecular weigh of 298 Daltons and partition coefficient of 1.0). The rest is metabolized in the Krebs cycle mainly in the liver, kidneys and skeletal muscles. Each mol of trisodium citrate causes 3 moles of bicarbonate thus correctly, partially or completely, the metabolic acidosis resulting from renal failure. Ca and sodium (Na) are released into the systemic circulation. Trisodium citrate also increases the strong ion difference due to the high sodium concentration in the solution, thus increasing the buffering capacity. In parallel it is necessary the Ca replacement to maintain normal calcemia. The citrate also quenches magnesium, which can lead to a disturbance of this electrolyte.
There is no consensus on what the optimal blood flow (Qb) would be in continuous dialysis, especially when using regional citrate anticoagulation. Theoretically, a higher blood flow would prevent stasis in the system and thus decrease the risk of filter coagulation. Studies show conflicting results. For example, one study evaluated increasing Qb from 150 to 250 mL/min and showed that circuit useful life and the chance of coagulation of the extracorporeal system were similar between the two groups. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultra-filtrated flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher the convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range.
Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing blood flow, citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could lead to citrate overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when the maximum capacity of citrate metabolization is not reached and there is an excess of citrate infusion relative to the buffering requirement. The total Ca/systemic ionic Ca ration remains normal, below 2.5. The oversupply of citrate can be easily corrected by decreasing the bicarbonate concentration of the dialysate, increasing the dialysate dose or decreasing the citrate infusion.
Therefore, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients with AKI undergoing continuous venovenous hemodiafiltration (CVVHDF), regional anticoagulation with citrate during increased blood flow.
Hypothesis: Increasing blood flow during continuous venovenous hemodiafiltration prevents stasis in the system and thus reduces the risk of filter coagulation. Blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range. Therefore, it is expected that higher blood flow (250 mL/min) will reduce the FF and concomitantly prolong the life of the filter.
- Conditions
- Acute Kidney Injury
- Being tested
- Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration
- Keywords
- Continuous renal replacement therapy, Blood flow, Filtration fraction
- Medical subject headings
- Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltrationOther
Patients will be exposed to continuous venovenous renal therapy with distinct blood flows in 2 periods, to be defined by draw. The control group will have a flow of 150ml/min and the intervention group 250ml/min. Therapy is intended for a period of 72 hours (maximum defined by the manufacturer); with a 6-hour "washout" and, after that, the arm is changed to be exposed to the other blood flow.
| Study group | Role | What they receive |
|---|---|---|
| Qb150 | Experimental | This group will be exposed to continuous venovenous therapy with a blood flow of 150ml/min; already standardized by the institution; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency.
Both groups will have a "wash out" of 6 hours before crossing the arms of the work. Receives: Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration |
| Qb 250 | Active comparator | This group will be exposed to continuous venovenous therapy with a blood flow of 250ml/min; experimental group to evaluate increased blood flow and filter durability; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency.
Both groups will have a "wash out" of 6 hours before crossing the arms of the work. Receives: Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analyze filter/system useful life
Evaluate the duration of the continuous hemodiafiltration filter according to changes in blood flow
Measured: 72 hours per filter
Secondary outcomes (8)
Examine the system pressures
Assess changes in system pressures during the 2 blood flows (transmembrane pressure, filter pressure and access pressure)
Measured: 72 hours per filter
Assess filtration fraction variation
Assess filtration fraction variation during the 2 blood flows
Measured: 72 hours per filter
Electrolytic control - Potassium
Assess changes in potassium (changes from baseline)
Measured: 72 hours per filter (dosage every 12 hours according to protocol)
Electrolytic control - Sodium
Assess changes in sodium (changes from baseline)
Measured: 72 hours per filter (dosage every 12 hours according to protocol)
Acid-base balance - blood pH
Assess changes in blood pH during the 2 blood flows (changes from baseline)
Measured: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - sodium bicarbonate
Assess changes in sodium bicarbonate during the 2 blood flows (changes from baseline)
Measured: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - base excess
Assess changes in base excess during the 2 blood flows (changes from baseline)
Measured: 72 hours per filter (venous blood gas analysis every 12 hours)
Mortality of the cohort
Assess the overall mortality of the cohort in 30, 60 and 90 days
Measured: 30, 60 and 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2023
- Study start9 Jan 2023
- Primary completion9 Jan 2023
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- 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
- Crossover
- Model description
- This is a randomized, crossover, single-center study, with inclusion of patients over a period of 11 months, between January 9, 2023 and November 30, 2023. We aim to include 27 patients. Randomized by raffle, which will be carried out manually in blocks divided into 3 envelopes numbered from 01 to 03, and within them will contain 9 papers, also numbered from 1 to 27 with the definition of control group and experimental group. Following the order from 01 to 03, the envelopes will have: envelope 1: 9 samples (5 for control group and 4 for experimental group); envelope 2: 9 samples (4 for control group and 5 for experimental group); envelope 3: 9 samples (5 for control group and 4 for experimental group). Groups: Qb150 (control group) (blood flow 150 mL/min), Qb250 (experimental group) (blood flow 250 mL/min). Time for each treatment: 72 hours. Crossover: after 72 hours. Treatment pause (wash-out): 4 (minimum) to 6 (maximum) hours.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Israelita Albert Einstein
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lucas T Avila Neto, Principal investigator, Hospital Israelita Albert Einstein
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05796661
- Sponsor's protocol ID
- CRRT-QbTrial
- Status last verified
- Jan 2024
- First submitted
- 14 Mar 2023
- Last updated
- 10 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021 Jul 15;7(1):52. doi: 10.1038/s41572-021-00284-z.
PubMed 34267223Fuhrman DY, Kellum JA. Acute Kidney Injury in the Intensive Care Unit: Advances in the Identification, Classification, and Treatment of a Multifactorial Syndrome. Crit Care Clin. 2021 Apr;37(2):xiii-xv. doi: 10.1016/j.ccc.2021.01.001. Epub 2021 Feb 13. No abstract available.
PubMed 33752867Bellomo R, Baldwin I, Ronco C, Kellum JA. ICU-Based Renal Replacement Therapy. Crit Care Med. 2021 Mar 1;49(3):406-418. doi: 10.1097/CCM.0000000000004831. No abstract available.
PubMed 33555775Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available.
PubMed 22890468Khadzhynov D, Schelter C, Lieker I, Mika A, Staeck O, Neumayer HH, Peters H, Slowinski T. Incidence and outcome of metabolic disarrangements consistent with citrate accumulation in critically ill patients undergoing continuous venovenous hemodialysis with regional citrate anticoagulation. J Crit Care. 2014 Apr;29(2):265-71. doi: 10.1016/j.jcrc.2013.10.015. Epub 2013 Nov 11.
PubMed 24360392Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R. A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med. 2015 Aug;43(8):1622-9. doi: 10.1097/CCM.0000000000001004.
PubMed 25853591Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, Saudan P. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care. 2015 Mar 18;19(1):91. doi: 10.1186/s13054-015-0822-z.
PubMed 25881975Meersch M, Kullmar M, Wempe C, Kindgen-Milles D, Kluge S, Slowinski T, Marx G, Gerss J, Zarbock A; SepNet Critical Care Trials Group. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial. BMJ Open. 2019 Jan 21;9(1):e024411. doi: 10.1136/bmjopen-2018-024411.
PubMed 30670518Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, Dimski T, Tyczynski B, Jahn M, Mulling N, Mehrlander M, Rosenberger P, Marx G, Simon TP, Jaschinski U, Deetjen P, Putensen C, Schewe JC, Kluge S, Jarczak D, Slowinski T, Bodenstein M, Meybohm P, Wirtz S, Moerer O, Kortgen A, Simon P, Bagshaw SM, Kellum JA, Meersch M; RICH Investigators and the Sepnet Trial Group. Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial. JAMA. 2020 Oct 27;324(16):1629-1639. doi: 10.1001/jama.2020.18618.
PubMed 33095849Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003 Oct;31(10):2450-5. doi: 10.1097/01.CCM.0000084871.76568.E6.
PubMed 14530750Bauer E, Derfler K, Joukhadar C, Druml W. Citrate kinetics in patients receiving long-term hemodialysis therapy. Am J Kidney Dis. 2005 Nov;46(5):903-7. doi: 10.1053/j.ajkd.2005.07.041.
PubMed 16253731Yu W, Zhuang F, Ma S, Fan Q, Zhu M, Ding F. Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation. Nephron. 2019;141(2):119-127. doi: 10.1159/000494693. Epub 2018 Nov 16.
PubMed 30448847Schneider AG, Journois D, Rimmele T. Complications of regional citrate anticoagulation: accumulation or overload? Crit Care. 2017 Nov 19;21(1):281. doi: 10.1186/s13054-017-1880-1.
PubMed 29151020AYRES, M., AYRES Jr, M., AYRES, D. L., SANTOS, A. A. S. Bioestat 5.3 aplicações estatísticas nas áreas das ciências biológicas e médicas. Belém: IDSM, 2007.364p.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Filters Useful Life, Metabolic Control, Electrolyte Profile and Acid-base Balance During Regional Anticoagulation With 4% Trisodium Citrate in Patients Undergoing CVVHDF: Effects of Increased Blood Flow
- ClinicalTrials.gov ID
- NCT05796661
- Acronym / sponsor ID
- CRRT-QbTrial
- Conditions
- Acute Kidney Injury
- Keywords
- Continuous renal replacement therapy, Blood flow, Filtration fraction
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Hospital Israelita Albert EinsteinUniversity, hospital or other
- Study start
- 9 Jan 2023 (actual)
- Primary completion
- 9 Jan 2023 (actual)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 3 Apr 2023 (actual)
- 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.
Acute Kidney Injure (AKI) is a syndrome with high incidence and prevalence in Intensive Care Units (ICU). It is estimated that 50% of the in the sector present AKI at some point and 10 to 15% require renal replacement therapy (RRT). Although studies do not show the superiority of continuous methods, the most severely ill patients are directed to this type of RRT. A disadvantage of continuous therapies is the need for anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture).
On the one hand, ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter clotting. There is no consensus on what would be the optimal blood flow (Qb) in continuous dialysis, especially when regional citrate anticoagulation (RCA) is used. Theoretically, a higher flow rate would prevent stasis in the system and decrease the risk of filter clotting. Studies show conflicting results. Increasing Qb from 150 to 250 mL/min showed that circuit life and the chance of coagulation were similar. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow. Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter. Therefore, the higher the convection rate, the higher the blood flow should be to keep the FF in the optimal range. Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing the blood flow, the citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could cause its overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when its maximum metabolizing capacity is not reached and there is an excess of citrate infusion relative to the buffering requirement. Thus, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients undergoing continuous venovenous hemodiafiltration (CVVHDF), regional citrate anticoagulation during blood flow augmentation.
Detailed description
Acute kidney injury (AKI) is a clinical syndrome with a high incidence and prevalence in Intensive care units (ICU). It is estimated that 50% of ICU patients have AKI at some point.
About 10-15% of these individuals require renal replacement therapy (RRT). Although studies have not conclusively shown the superiority of continuous methods, the most severe patients are usually referred for this type of therapy.
The main indications for continuous therapies are hemodynamic instability, cardiogenic shock, severe respiratory insufficiency, risk situations for brain edema, hypercatabolism, need for strict volume control, acute liver disease and major sodium disturbances. One of the main disadvantages of continuous therapies is the necessity of anticoagulation. Critically ill patients have a pro-clotting state (inflammation) and several risk factors for bleeding (coagulopathies, postoperative, large vessel puncture). On the one hand, the lack or ineffective anticoagulation compromises the efficiency of the procedure, shortens the life of the extracorporeal system, consumes resources and increases blood loss due to unexpected and early filter coagulation. On the other hand, excessive use of anticoagulants, especially heparin, is associated with bleeding and increased transfusions.
In this scenario, regional anticoagulation with citrate (RCA) has become the method of choice in the different modalities of continuous dialysis. When compared to heparin, the use of regional citrate anticoagulation is associated with less bleeding and transfusion need and longer life of the extracorporeal system. It also seems to decrease endothelial activation, neutrophil degranulation and activation of the complement system.
The anticoagulate property of citrate is based on its binding to calcium (Ca). Citrate quenches Ca in the extracorporeal system, an essential cofactor in several steps of coagulation. Optimal anticoagulation is achieved when ionic Ca concentration in the extracorporeal circuit is maintained between 0.25 and 0.35 mmol/L. This is usually achieved with a citrate level in the circuit around 4mmol/L of blood. Depending on the modality chosen and other factors, up to 60% of the citrate-Ca complex is eliminated during passage through the filter (molecular weigh of 298 Daltons and partition coefficient of 1.0). The rest is metabolized in the Krebs cycle mainly in the liver, kidneys and skeletal muscles. Each mol of trisodium citrate causes 3 moles of bicarbonate thus correctly, partially or completely, the metabolic acidosis resulting from renal failure. Ca and sodium (Na) are released into the systemic circulation. Trisodium citrate also increases the strong ion difference due to the high sodium concentration in the solution, thus increasing the buffering capacity. In parallel it is necessary the Ca replacement to maintain normal calcemia. The citrate also quenches magnesium, which can lead to a disturbance of this electrolyte.
There is no consensus on what the optimal blood flow (Qb) would be in continuous dialysis, especially when using regional citrate anticoagulation. Theoretically, a higher blood flow would prevent stasis in the system and thus decrease the risk of filter coagulation. Studies show conflicting results. For example, one study evaluated increasing Qb from 150 to 250 mL/min and showed that circuit useful life and the chance of coagulation of the extracorporeal system were similar between the two groups. On the other hand, blood flow is important for maintaining the filtration fraction (FF), the ratio of ultra-filtrated flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher the convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range.
Since the anticoagulation capacity of citrate is dependent on its concentration, around 4 mmol/L of blood, by increasing blood flow, citrate infusion is proportionally increased. Theoretically, the higher citrate load offered should be metabolized and, in theory, could lead to citrate overload with the occurrence of metabolic alkalosis and hypernatremia. This situation occurs when the maximum capacity of citrate metabolization is not reached and there is an excess of citrate infusion relative to the buffering requirement. The total Ca/systemic ionic Ca ration remains normal, below 2.5. The oversupply of citrate can be easily corrected by decreasing the bicarbonate concentration of the dialysate, increasing the dialysate dose or decreasing the citrate infusion.
Therefore, we intend to evaluate filter useful life, metabolic control, electrolyte profile and acid-base balance in ICU patients with AKI undergoing continuous venovenous hemodiafiltration (CVVHDF), regional anticoagulation with citrate during increased blood flow.
Hypothesis: Increasing blood flow during continuous venovenous hemodiafiltration prevents stasis in the system and thus reduces the risk of filter coagulation. Blood flow is important for maintaining the filtration fraction (FF), the ratio of ultrafiltrate flow to plasma flow (blood flow minus hematocrit). Ideally, the FF should be kept below 25% to avoid hemoconcentration and coagulation of the filter capillary fibers. So the higher convection rate (ultrafiltration), the higher the blood flow should be to keep the FF in the optimal range. Therefore, it is expected that higher blood flow (250 mL/min) will reduce the FF and concomitantly prolong the life of the filter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a randomized, crossover, single-center study, with inclusion of patients over a period of 11 months, between January 9, 2023 and November 30, 2023. We aim to include 27 patients. Randomized by raffle, which will be carried out manually in blocks divided into 3 envelopes numbered from 01 to 03, and within them will contain 9 papers, also numbered from 1 to 27 with the definition of control group and experimental group. Following the order from 01 to 03, the envelopes will have: envelope 1: 9 samples (5 for control group and 4 for experimental group); envelope 2: 9 samples (4 for control group and 5 for experimental group); envelope 3: 9 samples (5 for control group and 4 for experimental group). Groups: Qb150 (control group) (blood flow 150 mL/min), Qb250 (experimental group) (blood flow 250 mL/min). Time for each treatment: 72 hours. Crossover: after 72 hours. Treatment pause (wash-out): 4 (minimum) to 6 (maximum) hours.
| Arm | Type | Receives |
|---|---|---|
| Qb150 | Experimental | Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltrationThis group will be exposed to continuous venovenous therapy with a blood flow of 150ml/min; already standardized by the institution; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency. Both groups will have a "wash out" of 6 hours before crossing the arms of the work. |
| Qb 250 | Active comparator | Other: Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltrationThis group will be exposed to continuous venovenous therapy with a blood flow of 250ml/min; experimental group to evaluate increased blood flow and filter durability; for a maximum time of 72 hours or interrupted sooner if the system clots or the filter loses patency. Both groups will have a "wash out" of 6 hours before crossing the arms of the work. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (4 listed)
- Age < 18 years.
- Weight < 50 Kg.
- Refusal to participate in the study (absence of informed consent).
- Patient with chronic kidney disease on dialysis
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 |
|---|---|---|
| Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltrationPatients will be exposed to continuous venovenous renal therapy with distinct blood flows in 2 periods, to be defined by draw. The control group will have a flow of 150ml/min and the intervention group 250ml/min. Therapy is intended for a period of 72 hours (maximum defined by the manufacturer); with a 6-hour "washout" and, after that, the arm is changed to be exposed to the other blood flow. | Other | Qb 250, Qb150 |
Primary outcome
Analyze filter/system useful life
Time frame: 72 hours per filter
Evaluate the duration of the continuous hemodiafiltration filter according to changes in blood flow
8 secondary outcomes
Examine the system pressures
Time frame: 72 hours per filter
Assess filtration fraction variation
Time frame: 72 hours per filter
Electrolytic control - Potassium
Time frame: 72 hours per filter (dosage every 12 hours according to protocol)
Electrolytic control - Sodium
Time frame: 72 hours per filter (dosage every 12 hours according to protocol)
Acid-base balance - blood pH
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - sodium bicarbonate
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Acid-base balance - base excess
Time frame: 72 hours per filter (venous blood gas analysis every 12 hours)
Mortality of the cohort
Time frame: 30, 60 and 90 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2024.
- Background: PubMed 34267223Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ. Acute kidney injury. Nat Rev Dis Primers. 2021 Jul 15;7(1):52. doi: 10.1038/s41572-021-00284-z.
- Background: PubMed 33752867Fuhrman DY, Kellum JA. Acute Kidney Injury in the Intensive Care Unit: Advances in the Identification, Classification, and Treatment of a Multifactorial Syndrome. Crit Care Clin. 2021 Apr;37(2):xiii-xv. doi: 10.1016/j.ccc.2021.01.001. Epub 2021 Feb 13. No abstract available.
- Background: PubMed 33555775Bellomo R, Baldwin I, Ronco C, Kellum JA. ICU-Based Renal Replacement Therapy. Crit Care Med. 2021 Mar 1;49(3):406-418. doi: 10.1097/CCM.0000000000004831. No abstract available.
- Background: PubMed 22890468Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012;120(4):c179-84. doi: 10.1159/000339789. Epub 2012 Aug 7. No abstract available.
- Background: PubMed 24360392Khadzhynov D, Schelter C, Lieker I, Mika A, Staeck O, Neumayer HH, Peters H, Slowinski T. Incidence and outcome of metabolic disarrangements consistent with citrate accumulation in critically ill patients undergoing continuous venovenous hemodialysis with regional citrate anticoagulation. J Crit Care. 2014 Apr;29(2):265-71. doi: 10.1016/j.jcrc.2013.10.015. Epub 2013 Nov 11.
- Background: PubMed 25853591Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R. A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med. 2015 Aug;43(8):1622-9. doi: 10.1097/CCM.0000000000001004.
- Background: PubMed 25881975Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, Saudan P. Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial. Crit Care. 2015 Mar 18;19(1):91. doi: 10.1186/s13054-015-0822-z.
- Background: PubMed 30670518Meersch M, Kullmar M, Wempe C, Kindgen-Milles D, Kluge S, Slowinski T, Marx G, Gerss J, Zarbock A; SepNet Critical Care Trials Group. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill patients with acute kidney injury (RICH) trial: study protocol for a multicentre, randomised controlled trial. BMJ Open. 2019 Jan 21;9(1):e024411. doi: 10.1136/bmjopen-2018-024411.
- Background: PubMed 33095849Zarbock A, Kullmar M, Kindgen-Milles D, Wempe C, Gerss J, Brandenburger T, Dimski T, Tyczynski B, Jahn M, Mulling N, Mehrlander M, Rosenberger P, Marx G, Simon TP, Jaschinski U, Deetjen P, Putensen C, Schewe JC, Kluge S, Jarczak D, Slowinski T, Bodenstein M, Meybohm P, Wirtz S, Moerer O, Kortgen A, Simon P, Bagshaw SM, Kellum JA, Meersch M; RICH Investigators and the Sepnet Trial Group. Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury: A Randomized Clinical Trial. JAMA. 2020 Oct 27;324(16):1629-1639. doi: 10.1001/jama.2020.18618.
- Background: PubMed 14530750Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003 Oct;31(10):2450-5. doi: 10.1097/01.CCM.0000084871.76568.E6.
- Background: PubMed 16253731Bauer E, Derfler K, Joukhadar C, Druml W. Citrate kinetics in patients receiving long-term hemodialysis therapy. Am J Kidney Dis. 2005 Nov;46(5):903-7. doi: 10.1053/j.ajkd.2005.07.041.
- Background: PubMed 30448847Yu W, Zhuang F, Ma S, Fan Q, Zhu M, Ding F. Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation. Nephron. 2019;141(2):119-127. doi: 10.1159/000494693. Epub 2018 Nov 16.
- Individual participant dataSharing planned: No
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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.
Lucas T Avila Neto principal investigator
Hospital Israelita Albert Einstein
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Effects of increased blood flow during regional anticoagulation with 4% trisodium citrate in patients undergoing continuous venovenous hemodiafiltration in people with Acute Kidney Injury, run by Hospital Israelita Albert Einstein at 1 site in Brazil.
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 0 inclusion and 4 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 10 Jun 2024. 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 Brazil. 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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Analyze filter/system useful life (time frame: 72 hours per filter). 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 NCT05796661, which also lists 14 linked publications.
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 10 Jun 2024.