CoV-Hep Study: Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19

CoV-Hep Study: Randomized and Paired Clinical Trial Comparing Regional Anticoagulation Modalities in Continuous Venous Venous Hemodialysis in Patients With COVID-19

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.

Study Overview

• Status: Completed
• Conditions: Covid19; Acute Kidney Injury
• Intervention / Treatment: Drug: unfractionated Heparin

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.

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05403-010
      • University of Sao Paulo General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control group; Patients on continuous hemodialysis (blood flow 150 ml / min, dose of 30 ml / kg / h) receiving anticoagulation with sodium citrate at 4 mmol / l.
EXPERIMENTAL: Intervention group; 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.	Drug: unfractionated Heparin; Addition of unfractioned heparin to CVVHD system already running under citrate regional anticoagulation.; Other Names: No associated drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clotted dialyzers	The percentage of clotted dialyzers within 72 hours in each of the studied groups.	Day 3 of dialysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-free of clotting	Number of hours until a dialyzer clots in the first 72 hours of dialysis	Day 3 of dialysis
Number of dialyzers used	The amount of dialyzers used in the first 72 hours of hemodialysis	Day 3 of dialysis
Pressure variation	Variation in dialysis system and vascular access pressures in the first 72 h of dialysis	Day 3 of dialysis
Urea sieving	Variation in urea sieving between the first, second and third days of dialysis	Day 3 of dialysis
Downtime of dialysis	Time of dialysis stop due to clotting in the first 72 hours	Day 3 of dialysis

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Principal Investigator: Paulo Lins, MD, University of Sao Paulo General Hospital; Principal Investigator: Camila Rodrigues, MD, PhD, University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 29, 2020
• Primary Completion (ACTUAL): March 31, 2021
• Study Completion (ACTUAL): April 3, 2021

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (ACTUAL): July 27, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 8, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: acute kidney injury; anticoagulation; covid-19; heparin; citrate; continuous venovenous hemodialysis
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; COVID-19; Acute Kidney Injury; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: U1111-1252-0194; 33351120.0.0000.0068 (OTHER: CAAE / CONEP / CEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No