Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome.

Nephrotic Syndrome Clinical Trial

— ENOX-inNS  

Official title:

Assessment of Coagulation Disorders and of Enoxaparin's Anti-Xa Activity, When Used for Thromboprophylaxis, in Severe Nephrotic Syndrome.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04558892
• Other study ID #: 5/8952 (443)
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: October 1, 2015
• Est. completion date: November 30, 2018

Study information

• Verified date: September 2020
• Source: Military Institute of Medicine, Poland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to test the hypothesis that enoxaparin efficacy is reduced in severe nephrotic syndrome. Another purpose is to compare two dosing regimens.

Description:

Nephrotic syndrome (NS) is a rare clinical condition characterized by proteinuria exceeding >3.5 g/24h, hypoalbuminemia, dyslipidemia and edema and is associated with hypercoagulable state. In severe cases, with serum albumin ≤2.5 g/dL, the risk of venous thromboembolic events (VTE) is particularly high, and pharmacological prophylaxis is recommended. However, there is a limited evidence of its efficacy and optimal dosing.

The study is designed as 3 arms clinical trial, with 2 study groups and a single control group. The study groups will include patients with severe NS parallelly, alternately assigned (1:1) into two enoxaparin dosing regimens. The control group will consisted of individuals without proteinuria and edema, similar in terms of age, anthropometric features and renal function to NS patients, who will be administered a standard enoxaparin dose. A peak anti-Xa activity at the steady state will be measured to determine the plasma concentration of enoxaparin. Additional laboratory tests for markers of NS severity, renal function and coagulation system proteins will be performed. The overhydration and body water compartments will be assessed using bioimpedance spectroscopy technique. Nephrotic patients will be followed up by 12 months to assess overt VTE and adverse events associated with enoxaparin use.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 65
• Est. completion date: November 30, 2018
• Est. primary completion date: November 30, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Severe NS, defined as proteinuria exceeding 3.5 g/24h or 50 mg/kg/24h and serum albumin =2.5 g/dL;

• eGFR =30 mL/min/1.73 m2.

Exclusion Criteria:

• Body mass index (BMI) =40 kg/m2;

• Low body mass (<45 kg for female, <57 kg for male);

• Acute VTE;

• Previously introduced anticoagulation (due to comorbidities);

• Contraindications for enoxaparin;

• Pregnancy.

Related Conditions & MeSH terms

• Nephrosis
• Nephrotic Syndrome
• Syndrome
• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Enoxaparin

Locations

Country	Name	City	State
Poland	Military Institute of Medicine	Warsaw	Masovian District

Sponsors (1)

Lead Sponsor	Collaborator
Military Institute of Medicine, Poland

Country where clinical trial is conducted

Poland, 

References & Publications (1)

Matyjek A, Rymarz A, Nowicka Z, Literacki S, Rozmyslowicz T, Niemczyk S. Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome-A Single Center Prospective Study. J Clin Med. 2021 Dec 6;10(23):5709. doi: 10.33 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Venous thromboembolic events.	Clinically overt episode of VTE.	Follow-up period of 1 year from enrollment.
Other	Adverse events of enoxaparin.	Episodes of minor and major bleeding or heparin-induced thrombocytopenia.	Follow-up period of 1 year from enrollment.
Primary	Therapeutic enoxaparin's anti-Xa activity in nephrotic syndrome.	Anti-Xa activity values = 0.3 IU/mL in the steady state of enoxaparin concentration, on average between days 3 and 5.	Average: Day 3-5
Primary	Minimum threshold of enoxaparin's anti-Xa activity.	Anti-Xa activity values = 0.2 IU/mL in the steady state of enoxaparin concentration on average between days 3 and 5.	Average: Day 3-5
Secondary	Severity of nephrotic syndrome.	Serum or/and urinary concentration of laboratory markers of disease.	Day 0, Day 3-5
Secondary	Coagulation system protein.	Plasma concentration or activity of secondary hemostasis system protein (clotting factors, fibrinolysis factors, regulatory molecules).	Day 0, Day 3-5
Secondary	Renal function.	Estimated glomerular filtration rate (eGFR) calculated with simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula.	Day 0, Day 3-5
Secondary	Edema.	Clinical evaluation of edema using 3-stages scale (I: <5 kg, II: 5-10 kg, III: >10 kg) at enrollment and on the day of measuring anti-Xa activity of enoxaparin.	Day 0, Day 3-5
Secondary	Overhydration.	Overhydration measured by bioimpedance spectroscopy on the day of measuring anti-Xa activity of enoxaparin.	Day 3-5