Sonoclot to Evaluate Thrombotic Risk in Proteinuric Pregnancy

There is a lack of consensus on whether women with proteinuric kidney disease benefit from prophylactic anticoagulation during pregnancy to reduce the risk of venous thromboembolism.

This pilot study will investigate the feasibility of obtaining thrombosis profile data using a viscoelastic haemostasis monitor - Sonoclot - from pregnant women with kidney disease, and exploratory analyses to elucidate correlations between output values and clinical parameters

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Diseases; Pregnancy Complications; Venous Thromboembolism; Proteinuria in Pregnancy
• Intervention / Treatment: Diagnostic test: Viscoelastic haemostasis monitor output

Detailed Description

Pregnancy is a risk factor for women developing blood clots in veins (VTE). The risk is highest towards the end of pregnancy and in the few weeks following delivery. VTE can cause swollen painful legs due to clots in the deep veins (DVT) and/or blood clots in the lung vessels leading to chest pain, breathlessness and loss of blood pressure. VTE is the leading direct cause of death in pregnant women in the UK (affecting 1.4 per 100,000 pregnancies). Additional risk factors for VTE (including obesity, family history, previous history of blood clots and Caesarean section) are routinely valuated through standard care and treatment to thin blood with low molecular weight heparin (LWMH) injections is offered to those at highest risk. Women with kidney disease comprise a very small proportion of all pregnancies and are hence under-represented in large-scale studies to evaluate VTE risk.

Outside of pregnancy, patients with kidney conditions associated with heavy leakage of protein into urine through damaged microscopic filters (glomeruli) plus low blood protein plus swelling (the "nephrotic syndrome") have an increased risk of VTE. VTE risk is increased as a result of (a) concentration of blood within blood vessels due to fluid leak into tissues, (b) decreased flow of blood through veins due to circulating volume and decreased mobility and (c) an imbalanced loss of proteins in urine that favour or inhibit blood clotting. There is evidence to support blood thinning treatment to reduce the risk of VTE in patients with one cause of nephrotic syndrome - membranous nephropathy - and many clinicians choose to offer blood thinning treatment to patients with other causes of nephrotic syndrome if they believe the patient is at increased risk of clots.

There are no clinical data to confirm a benefit of blood thinning treatments to prevent VTE in pregnant women with nephrotic syndrome, but, faced with the lack of published studies, consensus guidelines published in 2018 recommend that women with nephrotic syndrome should be treated during pregnancy and for 6 weeks after birth.

There is a lack of consensus on whether women with less severe protein leak during pregnancy should be offered blood thinning injections. An international survey of clinicians caring for women with these conditions reports a wide range in practice from some offering treatment to all with a protein leak (urine protein:creatinine ratio) >100mg/mmol, to others only considering treatment if leak was >300mg/mmol AND evidence of low blood protein AND swelling.

VTE prophylaxis with LMWH is standard of care for medical in-patients and for out-patient treatment in pregnant women identified to be at increased VTE risk. Although LMWH treatment is not associated with any adverse pregnancy outcomes, it is uncomfortable, inconvenient and can interfere with delivery plans if spinal or epidural anesthetic is required.

There are, therefore, women receiving LMWH prophylaxis because of increased urine protein leak despite inadequate evidence to prove the benefit of this strategy and insufficient clinical tools to triage risk profiles for these patients.

There are no routine laboratory tests that offer a direct measurement of thrombotic risk. Sonoclot is established technology that has been utilised to quantify bleeding risk after cardiac surgery and disseminated clotting abnormalities, and adequacy of anticoagulation in haemodialysis patients and during treatment with direct acting oral anticoagulants. In addition to predicting bleeding risk, results also identify clotting risk. This has previously been studied in women taking oral contraception and in normal pregnancy with both identifying patterns consistent with increased thrombotic risk during pregnancy or with combined oral contraceptive use.

This study aims to assess the feasibility of conducting a clinical trial using Sonoclot results to identify which pregnant women with kidney disease are at increased risk of VTE and which are not, to define treatment protocols with LMWH prophlyaxis. This pilot study will assess the correlations between Sonoclot results, urine protein leak, gestational age, routine laboratory test results and routine VTE risk assessment tools.

• Study Type: Observational
• Enrollment (Actual): 13

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Pregnant women attending the combined renal-obstetric outpatient service at Nottingham University Hospitals NHS Trust, UK

Description

Inclusion Criteria:

• Confirmed pregnancy by ultrasound scanning or urine or serum beta-HCG
• Chronic kidney disease stage 1 to 5, defined as abnormalities of serum creatinine, urine constituents or renal tract anatomy for more than 3 months, or genetic traits associated with renal disease

Exclusion Criteria:

• Known primary thrombophilia (including factor V Leiden, prothrombin mutations, protein C deficiency, protein S deficiency)
• Treatment with low molecular weight heparin in 24 hours prior to consent
• Suspected or confirmed active pre-eclampsia or superimposed pre-eclampsia

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women with kidney disease; Pregnant women with kidney disease. No intervention.	Diagnostic test: Viscoelastic haemostasis monitor output; Observational

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteinuria (log) to clot time correlation	Univariate linear regression analysis of clot time vs log[urine protein:creatinine ratio]	Through study completion, an average of 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteinuria to clot time correlation	Univariate linear regression analysis of clot time vs urine protein:creatinine ratio	Through study completion, an average of 9 months
Proteinuria (<>100mg/mmol) to clot time correlation	Comparison of mean clot time vs urine protein:creatinine rate < or ≥ 100 mg/mmol	Through study completion, an average of 9 months
Proteinuria (<>300mg/mmol) to clot time correlation	Comparison of mean clot time vs urine protein:creatinine rate < or ≥ 300 mg/mmol	Through study completion, an average of 9 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory	Correlation of Sonoclot data with treatment options as per routine clinical care (aspirin, LMWH).	Through study completion, an average of 9 months

Collaborators and Investigators

• Sponsor: Nottingham University Hospitals NHS Trust
• Investigators: Principal Investigator: Matthew Hall, MB MD FRCP, Nottingham University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 25, 2021
• First Posted (Actual): November 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 4, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Pregnancy Proteinuria Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Urological Manifestations; Renal Insufficiency; Urination Disorders; Embolism and Thrombosis; Kidney Diseases; Renal Insufficiency, Chronic; Proteinuria; Thromboembolism; Venous Thromboembolism; Pregnancy Complications; Coagulants; Hemostatics
• Other Study ID Numbers: 19OB011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Anonymised and aggregated data available to share with collaborators

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.: Yes