Thrombin Generation Assay to Assess Thrombotic Risk in Nephrotic Patients (TGANephrotic)

Thrombin Generation Assay to Assess Thrombotic Risk and the Evolution of the Hypercoagulability Profile of Patients With Nephrotic Syndrome

The thromboembolic risk is increased during the nephrotic syndrome (NS) with an incidence of deep vein thrombosis 15%, pulmonary embolism of 10-30% and renal vein thrombosis of 25-37%. There is a hemostatic imbalance with urinary leakage of anticoagulant factors and increased hepatic synthesis of procoagulant factors, platelet hyperaggregability and a decrease in fibrinolytic activity. However, the identification of patients requiring anticoagulant prophylaxis remains imprecise.The thromboembolic risk is higher when the NS is related to extramembranous glomerulonephritis comparatively to others glomerulopathies. The reason of this difference is not still known. This risk increase with SN's severity and therefore with the decrease of albuminemia. Moreover, few studies have evaluated anticoagulant treatment efficacy during a NS, which clinical benefit depends also on hemorrhagic risk specific of each patient. Thus, the determination of the thrombotic risk and the modalities of anticoagulation are variable and perfectible during the NS.

We propose to use the thrombin generation test (TGT) to quantify the thromboembolic risk in patients with a NS and to follow its evolution during prophylactic anticoagulation and after remission of NS.

Study Overview

• Status: Not yet recruiting
• Conditions: Nephrotic Syndrome

Detailed Description

Thrombin generation test will be performed prospectively in nephrotic patients with various diseases (Minimal Change Disease (MCD), Malignant Nephrosclerosis (MN), Focal Segmental GlomeruloSclerosis (FSGS), diabetic glomerulopathy…) at diagnosis, during anticoagulant treatment (D8±3) and after disease remission (M6).

• Study Type: Observational
• Enrollment (Anticipated): 75

Contacts and Locations

• Study Contact: Name: Armance MARCHAL, MD; Phone Number: +33 1 56 01 60 43; Email: armance.marchal@aphp.fr
• Study Contact Backup: Name: Jean-Jacques BOFFA, MD, PhD; Phone Number: +33 1 56 01 60 29; Email: jean-jacques.boffa@aphp.fr

Study Locations

• France
  • Paris, France
    • Service de Néphrologie et Dialyses, Hôpital Tenon
    • Contact: Armance MARCHAL, MD; Phone Number: +33 1 56 01 60 29; Email: armance.marchal@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with nephrotic syndrome defined by albuminemia <3 g/dl and urinary protein/creatinine > 3g/g) admitted in the nephrology department of Tenon hospital; etiological diagnosis available; consenting to research and whose treatment and follow-up will be possible for at least 6 months.

Description

Inclusion Criteria:

• Nephrotic syndrome
• Known cause of nephrotic syndrome (renal biopsy and/or positive anti-PLA2R)

Exclusion Criteria:

- Active anticoagulation treatment before TGT

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the prognosticity of TGT in predicting the occurrence of a thromboembolic event at 6 months.	Number of thrombotic events at 6 months of follow-up	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Variation of TGT parameters (data combined considering latency, velocity, peak, amount of total thrombin formed) during the follow-up	To calculate the difference of TGT parameters between the time of acute phase of NS (at diagnosis = inclusion), and after NS remission.	Maximum 6 months (when albumin > 30 g/l)
Compare the theoric indications for anticoagulation therapy according to TGT parameters with those of the Lin R algorithm and "Kidney Disease: Improving Global Outcomes" (KDIGO) 2021	Percentage of anticoagulated patients versus theoric number, based on TGT results and available algorithms	At diagnosis = at inclusion

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Armance MARCHAL, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): March 31, 2024

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 21, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Nephrotic Syndrome; Thrombotic risk assessment
• Additional Relevant MeSH Terms: Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Syndrome; Nephrotic Syndrome; Nephrosis
• Other Study ID Numbers: APHP220213

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No