Oxidative Stress and Circulating Nuclear DNA (cfDNA) in Acute Kidney Injury and Continuous Renal Replacement Therapies.

NCT06646328 | Terminated Phase 4

• 2 other identifiers: FER-CIT-2016-012016-004361-12
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Acute kidney injury (AKI) is the inability of the kidneys to perform their functions of purifying and cleaning the blood. It is a frequent complication in hospitalized patients, especially in those admitted to the ICUs. In these situations is common to use machines to artificially and temporarily replace renal function so waste products that can be toxic are removed from the body. The purpose of this study is to assess the effectiveness and safety of two anticoagulation strategies of the extracorporeal purification system in critically ill patients with acute kidney injury treated with continuous renal replacement therapy (CRRT) evaluating the effect of both strategies in oxidative stress and extracellular nucleosomes and its influence on the recovery of renal function.

Conditions

Acute Kidney Injury

Keywords

Biocompatibility; Renal replacement therapies; Oxidative stress; Myeloperoxidase; Nucleosomes; Regional citrate anticoagulation; Heparin

Outcome Measures

Primary Outcomes (3)

• Recovery of renal function

  Impact of circulating nuclear DNA (cfDNA) and oxidative stress on duration of renal replacement therapy (RRT) in ICU.

  Through study completion, an average of 20 days.

• Recovery of renal function

  Impact of circulating nuclear DNA (cfDNA) and oxidative stress on change of Creatinine from baseline to ICU discharge.

  Through study completion, an average of 20 days.

• Recovery of renal function

  Impact of circulating nuclear DNA (cfDNA) and oxidative stress on change of Creatinine from baseline to hospital discharge.

  Through study completion, an average of 20 days.

Secondary Outcomes (14)

• Activation and elimination of free radicals

  24 hours

• Activation and elimination of free radicals

  24 hours

• Activation and elimination of biomarkers of inflammation

  24 hours

• Activation and elimination of biomarkers of inflammation

  24 hours

• Activation and elimination of biomarkers of cell damage

  24 hours

Study Arms (2)

Heparin

ACTIVE COMPARATOR

Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein. The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the heparin arm the anticoagulation technique to be used will be non-fractional heparin. Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration \[Ci\]) and postfilter (outlet filter plasma concentration \[Co\]) sites of the extracorporeal circulation circuit at different times.

Procedure: Central venous access; Device: Pump-assisted circuit; Drug: Heparin sodium; Procedure: Blood and ultrafiltrate samples

Citrate

EXPERIMENTAL

Central venous access will be achieved with a 13 Fr double lumen catheter placed into the internal jugular or femoral vein. The patient will be connected to the Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany) pump-assisted circuit with a high-flux synthetic membrane. In the citrate arm regional citrate anticoagulation of the extracorporeal purification system will be used to avoid coagulation of the circuit. Blood and ultrafiltrate samples will be taken from the prefilter (inlet filter plasma concentration \[Ci\]) and postfilter (outlet filter plasma concentration \[Co\]) sites of the extracorporeal circulation circuit at different times.

Procedure: Central venous access; Device: Pump-assisted circuit; Other: Regional citrate anticoagulation; Procedure: Blood and ultrafiltrate samples

Interventions

Central venous access PROCEDURE

Venous access will be achieved with a 13 Fr double lumen catheter into the internal jugular or femoral vein.

Citrate; Heparin

Pump-assisted circuit DEVICE

The pump-assisted circuit to be used will be Fresenius multiFiltrate (Fresenius Medical Care GmbH, Bad Homburg v.d.H., Germany). EMIC2® Fresenius Medical Care high-flux synthetic membrane will be used

Also known as: Continuous renal replacement therapy, CRRT

Citrate; Heparin

Heparin sodium DRUG

Non-fractional heparin will be used in one arm with an initial dose of 500-1000 IU/hour with adaptation of the infusion to the patient and the clotting time.

Also known as: Non-fractional heparin, Heparin

Heparin

Regional citrate anticoagulation OTHER

Regional citrate anticoagulation will be used in the other arm with an initial dose of 3 mmol/L and with a calcium reinfusion solution at an initial dose of 2 mmol/L, with adaptation of both infusions to the patient ionic calcium levels.

Citrate

Blood and ultrafiltrate samples PROCEDURE

Blood samples will be taken from the prefilter (inlet filter plasma concentration \[Ci\]) and postfilter (outlet filter plasma concentration \[Co\]) sites of the extracorporeal circulation circuit. The ultrafiltrate will be collected directly from the outlet of the hemofilter (ultrafiltrate concentration \[Cuf\]). The samples will taken at the beginning of CRRT (T0) and at the following times: T0, Ci; after 60 min (T1) and after 24 hours (T2) of CRRT, Ci, Co and Cuf. Venous access will be achieved with a 13 Fr double lumen catheter into the internal jugular or femoral vein.

Citrate; Heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult intensive care patients (age \> 18) admitted to the ICU with AKI requiring treatment with continuous renal replacement technique.
• Patients able to accept being included in the study by signing the Informed Consent (IC). If the patient can not give consent, family consent is requested and, by default, the opinion of the person of trust or designated decision, if present. If there is no family present, trusted person or legal representative designated, the possibility of deferred consent is not contemplated. In this case the patient will not be included in the study.

You may not qualify if:

• Age under 18 years old.
• Pregnancy and/or lactation.
• Terminal diseases or life expectancy lower than 48 hours.
• Increased risk of bleeding (defined as platelet count less than 40x109 / L, partial thromboplastin time (TTPA) over 60 seconds, prothrombin time (PT)international normalized ratio (INR) greater than 2.0 or recent major bleeding).
• Need of systemic anticoagulation therapy.
• Contraindication for heparin.
• Heparin-induced Thrombocytopenia (HIT).
• Hypercalcemia (\> 3 mmol / L).
• Severe Hepatitis: glutamic oxaloacetic transaminase (GOT) or glutamic pyruvic transaminase (GPT) \> 1000 IU / L.
• Cirrhosis.

Sponsors & Collaborators

• Fernando Sanchez: lead
• Hospital Universitario de la Plana: collaborator
• Hospital General Universitario de Castellón: collaborator

Study Sites (1)

Fernando Sánchez

Castellon, Castellon, 12004, Spain

Location

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Related Links

• SPAIN. 2015. BOE-A-2015-14082. Royal Decree 1090/2015, of December 4, regulating clinical trials with medicines, Committees of Ethics of Research with medicines and the Spanish Registry of Clinical Studies.
• EUROPEAN UNION. OJ L 158 27.5.2014. Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on clinical trials on medicinal products for human use and repealing Directive 2001/20 / EC.
• SPAIN. 2007. BOE-A-2007-12945. Law 14/2007, of July 3, on Biomedical Research which regulates biomedical research. Official Gazette of the State, July 4, 2007, 159, pp. 28826 to 28848.

MeSH Terms

Conditions

Acute Kidney Injury

Interventions

Continuous Renal Replacement Therapy; Heparin; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative; Glycosaminoglycans; Polysaccharides; Carbohydrates; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Investigative Techniques

Study Officials

• Fernando Sanchez, MD

  La Plana Health Department. Valencian Health Counseling

  STUDY CHAIR

• Fernando Sanchez, MD

  La Plana Health Department. Valencian Health Counseling

  STUDY DIRECTOR

• Fernando Sanchez, MD

  La Plana Health Department. Valencian Health Counseling

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Consultant of Intensive Care Medicine

Study Record Dates

• First Submitted: July 31, 2018
• First Posted: October 17, 2024
• Study Start: June 9, 2018
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: October 18, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)