Optimizing Anticoagulation in Pregnancies With Mechanical Heart Valves

A Prospective Multicenter Cohort Pilot Study Comparing Antithrombotic Regimens in Pregnancies With Mechanical Heart Valves

The purpose of this pilot study is to collect data on pregnancies with mechanical heart valves to see if using a blood thinner called low molecular weight heparin (LMWH) and low dose aspirin (LDA) is comparable to warfarin/vitamin K antagonist (VKA) to reduce the chance of clotting around the mechanical valve and improve survival. The study is a pilot study as the study investigators need to ensure that the blood levels needed for adequate amounts of LMWH and warfarin can be maintained during pregnancy to be able to compare LMWH and aspirin to warfarin. If this study shows that we can collect the tests that are needed for a larger study, the individuals' information who participated in this pilot study will be moved to the larger study. The larger study will compare survival, clot development and cardiac function as well as safety of these two common blood thinners.

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Anticoagulant Therapy; Prosthetic Heart Valve
• Intervention / Treatment: Drug: LMWH and LDA; Other: Vitamin K antagonists (e.g warfarin)+/- LDA; Other: Sequential therapy +/- LDA

Detailed Description

Pregnancies with mechanical heart valves (MHVs) have a substantial risk of thromboembolic events, hemorrhage, mortality and low live birth rates. The observational studies that have been published have been challenged by the lack of standardized regimens for antithrombotic agents (including standardized dosing and monitoring), standardized measurements of outcomes, and the observational nature. Notably, there are also limited data collected and described for maternal and neonatal safety and on cardiac morbidity such as left ventricular function (LVF) i.e., left ventricular ejection fraction, frequency of arrhythmias and valve competence after pregnancy. Individuals with MHVs are predominantly from low resource countries and optimizing maternal and fetal morbidity and mortality in these pregnancies should be prioritized similarly as other pregnancies. There is a need for a prospective controlled multicenter study as individual's centers do not have the patient volumes for risk assessment and many centers are in low resource settings. We will conduct a multicenter controlled prospective internal pilot pragmatic study comparing the two standard antithrombotic regimens (LMWH and LDA vs VKAs) for 100 pregnancies with MHVs. The sequential therapy regimen will be combined with the regimen of VKAs as most of the pregnancy is exposed to VKAs, but secondary analysis will be conducted separating the two groups. Patients will be recruited in obstetrical clinics before 12 weeks gestation.

The overall objective is to determine the optimal antithrombotic regimen for pregnancies with MHVs.

3.1 Primary Objective To assess feasibility of conducting a large prospective controlled (adherent to an anticoagulation regimen) study by determining

1) Enrollment rates a) patients enrolled/patients eligible, and b) consent rates (consent obtained/patients approached), 2) Protocol adherence, 3) Ability to accurately collect data and complete the eCRF, 4) Resources required for a larger study and, 5) To ensure accuracy of effect size as described above. 3.2 Secondary Objective(s) To determine the rate of

1. The composite outcome of all-cause maternal mortality (according to gestational age) and mechanical valve thrombosis and the sequelae, arterial embolism leading to organ/limb ischemia;
2. Maternal safety outcomes including A. The frequency of the individual outcomes of the composite outcome B. Cardiac morbidity including arrhythmias requiring electrical or medical cardioversion, cardiac arrest, left ventricular function and valve size following delivery C. Primary postpartum hemorrhage (hemorrhage within 24 hours of delivery and treated by transfusion or requiring critical care or return to surgery) D. Other hemorrhagic events as defined by ISTH criteria (https://bleedingscore.certe.nl/) all at birth and 12 weeks postpartum E. Other maternal adverse events as defined and categorized by MedDRA (https://www.meddra.org/).
3. Pregnancy safety outcomes A. Pregnancy loss at any gestation B. Proportion of preterm delivery (defined as delivery less than 37 weeks gestation) - stratified by spontaneous and iatrogenic preterm delivery, and C. Presence of preeclampsia and degree of severity according to current definitions
4. Fetal/neonatal safety outcomes A. Fetal and neonatal loss defined as miscarriage (fetal loss under 20 weeks of gestation), stillbirth (fetal loss between 20+1 weeks of gestation and birth) and neonatal death (death after birth and within the first 28 days of life).

B. Presence of embryopathy/fetopathy secondary to VKAs C. Small for gestational age neonates less than the 10th percentile for gestational age and D. Need for neonatal critical care.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nadine Shehata, MD; Phone Number: 4165865133; Email: nadine.shehata@sinaihealth.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X5
      • Recruiting
      • Mount Sinai Hospital
      • Contact: Nadine Shehata, MD; Phone Number: 4165865133; Email: nadine.shehata@sinaihealth.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Pregnant individuals with one or more MHVs
2. Who consent to participate
3. Are 18 years or older and
4. Less than 12 weeks gestation

Exclusion Criteria:

1. Have a platelet count less than 50 x 10(9)/L as there is an increased risk of bleeding with thrombocytopenia, and/or
2. Have active bleeding defined as bleeding resulting in a hemoglobin reduction ≥10 g/L or in hemodynamic instability.
3. Have new valve thrombosis identified immediately prior to pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LMWH and LDA; Therapeutic LMWH throughout pregnancy either using weight-based dosing or dosing according to peak and/or trough anti-Xa levels (measured after at least 4 days of starting or change of dose) and LDA	Drug: LMWH and LDA; 1) Therapeutic LMWH throughout pregnancy either using weight-based dosing or dosing according to anti-Xa levels. The initial dose will be a twice daily therapeutic dose of 1.35U/kg (pregnancy weight) of enoxaparin or 135 U/kg (pregnancy weight) of dalteparin using prefilled syringes titrated to the higher dose prefilled syringe (i.e., not below the pregnancy weight-based dosing).; The dose of therapeutic LMWH can be adjusted by anti-Xa (done at least after four days of the start of LMWH or change in LMWH dose) levels or by pregnancy weight however, weight and anti-Xa levels will be determined for all participants using LMWH. Pregnancy weight in kilograms is to be determined every month.; If therapeutic LMWH is adjusted according to anti-Xa levels, peak and trough anti-Xa levels (done at least after four days of the start of LMWH or change in LMWH dose) are to be sent every four weeks or weekly if there is a change in dose.
Other: Vitamin K antagonists (e.g warfarin)+/- LDA; VKA use will require INRs every two weeks or weekly (done at least 5 days after starting or changing the dose) if there is a change in doses to ensure an INR of 2.5 for and aortic MVR and 3 for a mitral MVR or two MHVs is met.	Other: Vitamin K antagonists (e.g warfarin)+/- LDA; VKAs during pregnancy: VKA use will require INRs every two weeks or weekly (done at least 5 days after starting or changing the dose) if there is a change in doses to ensure an INR of 2.5 for a patient with an aortic MVR (INR of 2 for the On-X AVR) and 3 for mitral MVR or two MHVs is met. LDA 81 mg to be added once pregnancy is confirmed.
Other: Sequential therapy +/-LDA; LMWH at 6 weeks gestation until 12 weeks gestation prescribed according to the regimens above then VKAs from 12 weeks gestation until 34-36 weeks gestation followed by twice daily LMWH. VKA use will require INRs every two weeks or weekly (done at least 5 days after starting or changing the dose) if there is a change in doses to ensure an INR of 2.5 for an aortic MVR (INR of 2 for the On-X AVR) and 3 for mitral MVR or two MHVs is met. LMWH will be administered twice daily according to pregnancy weight or anti-Xa level	Other: Sequential therapy +/- LDA; LMWH at 6 weeks gestation until 12 weeks gestation prescribed according to the regimens above then VKAs from 12 weeks gestation until 34-36 weeks gestation followed by twice daily LMWH according to doses above until delivery. LDA to be added when pregnancy is confirmed; Other Names: warfarin; LMWH; Vitamin K antagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome Measures	1) Enrollment rate: To determine enrollment rate as defined by the number of patients enrolled/patients eligible, and consent rates (consent obtained/patients approached)	At baseline
Adherence rate	To determine the adherence rate as defined as adherence to the anticoagulation regimen in 80% or more of the pregnancy.	From enrollment until birth.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary outcome measures	A composite outcome of all-cause mortality rate according to gestational age and maternal valve thrombosis rate	From enrollment until 12 weeks postpartum

Collaborators and Investigators

• Sponsor: Mount Sinai Hospital, Canada

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: November 26, 2025
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pregnancy; Low molecular weight heparin; warfarin; vitamin K antagonist; Anticoagulant therapy; Prosthetic heart valve
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrans; Carbohydrates; Heparin; Glycosaminoglycans; Polysaccharides; Coumarins; Benzopyrans; 4-Hydroxycoumarins; Warfarin; Heparin, Low-Molecular-Weight; acarboxyprothrombin
• Other Study ID Numbers: MVR221024; 5377 (Other Identifier: Clinical Trials Ontario)

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