Clinical trial NCT04558892: Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome.
Official title: Assessment of Coagulation Disorders and of Enoxaparin's Anti-Xa Activity, When Used for Thromboprophylaxis, in Severe Nephrotic Syndrome.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Nephrotic Syndrome
Keywords: Nephrotic syndrome
Enoxaparin
Low molecular weight heparin
Anti-Xa activity
Antifactor Xa
Venous thromboembolism
Lead sponsor: Military Institute od Medicine National Research Institute
Sponsor class: OTHER
First posted: 2020-09-22
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Therapeutic enoxaparin's anti-Xa activity in nephrotic syndrome.
timeFrame: Average: Day 3-5
measure: Minimum threshold of enoxaparin's anti-Xa activity.
timeFrame: Average: Day 3-5
Secondary outcomes:
measure: Severity of nephrotic syndrome.
timeFrame: Day 0, Day 3-5
measure: Coagulation system protein.
timeFrame: Day 0, Day 3-5
measure: Renal function.
timeFrame: Day 0, Day 3-5
measure: Edema.
timeFrame: Day 0, Day 3-5
measure: Overhydration.
timeFrame: Day 3-5
Other outcomes:
measure: Venous thromboembolic events.
timeFrame: Follow-up period of 1 year from enrollment.
measure: Adverse events of enoxaparin.
timeFrame: Follow-up period of 1 year from enrollment.
Locations:
city: Warsaw
country: Poland
facility: Military Institute of Medicine
state: Masovian District
Study officials:
affiliation: Military Institute of Medicine
name: Anna Matyjek, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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: 10.3390/jcm10235709.