Clinical trial NCT04487990: CoV-Hep Study: Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19
Official title: CoV-Hep Study: Randomized and Paired Clinical Trial Comparing Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Kidney Injury
Covid19
Keywords: acute kidney injury
continuous venovenous hemodialysis
anticoagulation
heparin
citrate
covid-19
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2020-07-27
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Clinical trial of treatment, randomized-controlled, parallel, open, with two arms
Primary purpose: TREATMENT

Brief summary: Since the emergence of the new strain of betacoronavirus (SARS-CoV-2) and its important clinical repercussions, it has been described that patients with its associated pneumonia (COVID-19) have high rates of thrombotic events, including reduction in the dialyzers patency when undergoing renal replacement therapy. Several strategies for preventing the early loss of dialysers are described, and regional anticoagulation based on citrate is the preferred modality for preventing this complication. On the other hand, in patients with SARS-CoV-2 there are already descriptions of endothelial inflammation and activation of the coagulation cascade, including studies demonstrating the benefit of heparinization of these patients. Thus, this study aims to compare two different anticoagulation strategies in patients infected with COVID-19 with continued venovenous hemodialysis (CVVHD). From the indication of CVVHD, patients will be screened according to eligibility criteria and, if they fit these parameters, they will be randomized into two groups: Group A - Standard regional anticoagulation based on Citrate associated with infusion of low doses of unfractionated heparin 10ui/kg/hour and Group B - Standard regional anticoagulation based on Citrate only. Patients will be randomized in blocks and followed for 72 hours. The primary endpoint is dialyzer patency at the end of 72 hours of clinical follow-up. Secondary objectives will be mortality, bleeding rate, drop in hematimetric indices, urea sieving, filter time in hours, down time of therapy, system and dialyser pressures (PBE and PTM). All patients will undergo a standard procedure with a prescribed dose of 30mL/Kg/H, blood flow of 150mL/minute and polysulfone dialyzer.

Detailed description: After randomization, patients will be allocated to one of two groups:

Control group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l. The dialysis system pressures, dialyzer patency and duration and bleeding rate will be assessed for 72 hours;

Intervention group (n = 45): patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l associated with unfractionated heparin at 10U / Kg / h. The dialysis system pressures, dialyzer patency and duration and bleeding rate will be assessed for 72 hours.

Eligibility criteria: Inclusion Criteria:

* Confirmed or probable SARS-CoV-2 infection;
* Presence of acute kidney injury with indication and agreement between ICU and nephrology teams for the introduction of renal continuous venous venous hemodialysis.

Exclusion Criteria:

* Hypersensitivity to any of the substances used in the study (Citric acid dextrosol 2.2% and unfractionated heparin);
* Previous diagnosis of coagulopathy or thrombophilia;
* Contraindication to the use of unfractionated heparin by the assistant team;
* Risk of citrate poisoning - (Lactate\> 30mg / dL, RNI\> 2.5, Total bilirubin\> 15mg / dL);
* Pregnancy

Primary outcomes:
measure: Clotted dialyzers
timeFrame: Day 3 of dialysis
Secondary outcomes:
measure: Time-free of clotting
timeFrame: Day 3 of dialysis
measure: Number of dialyzers used
timeFrame: Day 3 of dialysis
measure: Pressure variation
timeFrame: Day 3 of dialysis
measure: Urea sieving
timeFrame: Day 3 of dialysis
measure: Downtime of dialysis
timeFrame: Day 3 of dialysis
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: University of São Paulo General Hospital
state: SP
Study officials:
affiliation: University of São Paulo General Hospital
name: Paulo Lins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of São Paulo General Hospital
name: Camila Rodrigues, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Flumignan RL, Civile VT, Tinoco JDS, Pascoal PI, Areias LL, Matar CF, Tendal B, Trevisani VF, Atallah AN, Nakano LC. Anticoagulants for people hospitalised with COVID-19. Cochrane Database Syst Rev. 2022 Mar 4;3(3):CD013739. doi: 10.1002/14651858.CD013739.pub2.
citation: Lins PRG, de Albuquerque CCC, Assis CF, Rodrigues BCD, E Siqueira Campos BP, de Oliveira Valle E, Cabrera CPS, de Oliveira Gois J, Segura GC, Strufaldi FL, Mainardes LC, Ribeiro RG, Via Reque Cortes DDP, Lutf LG, de Oliveira MFA, Sales GTM, Smolentzov I, Reichert BV, Andrade L, Seabra VF, Rodrigues CE. Cov-hep study: heparin in standard anticoagulation based on citrate for continuous veno-venous hemodialysis in patients with COVID-19: a structured summary of a study protocol for a randomized controlled trial. Trials. 2020 Nov 11;21(1):920. doi: 10.1186/s13063-020-04814-0.