Clinical trial NCT05108389: Sonoclot to Evaluate Thrombotic Risk in Proteinuric Pregnancy
Official title: Sonoclot to Evaluate Thrombotic Risk in Proteinuric Pregnancy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pregnancy Complications
Proteinuria in Pregnancy
Chronic Kidney Diseases
Venous Thromboembolism
Keywords: Pregnancy Proteinuria Thrombosis
Lead sponsor: Nottingham University Hospitals NHS Trust
Sponsor class: OTHER
First posted: 2021-11-04
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Pregnant women attending the combined renal-obstetric outpatient service at Nottingham University Hospitals NHS Trust, UK

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Proteinuria (log) to clot time correlation
timeFrame: Through study completion, an average of 9 months
Secondary outcomes:
measure: Proteinuria to clot time correlation
timeFrame: Through study completion, an average of 9 months
measure: Proteinuria (<>100mg/mmol) to clot time correlation
timeFrame: Through study completion, an average of 9 months
measure: Proteinuria (<>300mg/mmol) to clot time correlation
timeFrame: Through study completion, an average of 9 months
Other outcomes:
measure: Exploratory
timeFrame: Through study completion, an average of 9 months
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals
Study officials:
affiliation: Nottingham University Hospitals
name: Matthew Hall, MB MD FRCP
role: PRINCIPAL_INVESTIGATOR
References: