NCT05451277

Brief Summary

Women with systemic lupus erythematosus (SLE) have a high risk of placenta-mediated complications, which can lead to substantial cardiac morbidities in affected women and their offspring. In addition, maternal autoantibodies, which are actively transferred across the placenta during pregnancy, can affect the cardiovascular health of SLE offspring. Hydroxychloroquine (HCQ) is effective in preventing adverse pregnancy outcomes in SLE and might be beneficial in preventing fetal cardiovascular damage mediated by maternal autoantibodies. However, there are concerns that HCQ might cause maternal and neonatal cardiac toxicity. A novel imaging technique (i.e. speckle tracking echocardiography), which allows early identification of cardiac dysfunction, has proven superior to any other in assessing cardiac function in mothers and neonates experiencing placenta-mediated complications and in identifying drug cardiotoxicity. Yet, there has been no study using speckle tracking echocardiography to evaluate the cardiovascular health of pregnant SLE women and their offspring, as well as the potential adverse cardiac effect of HCQ. Moreover, due to unavailability of assays, HCQ dosing in SLE is generally done blindly, without checking drug levels. To fill these key knowledge gaps, the investigators aim to: 1) assess the impact of placenta-mediated complications on maternal and neonatal cardiac function, 2) evaluate if HCQ exposure (as measured by whole-blood levels) is associated with maternal and neonatal outcomes including cardiac toxicity, and 3) determine the effect of maternal autoantibodies on neonatal cardiac function. Ultimately, our proposal will help optimize reproductive and cardiovascular outcomes in lupus women and their offspring.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
120

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Apr 2021

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2021

Completed
1.2 years until next milestone

First Submitted

Initial submission to the registry

June 23, 2022

Completed
18 days until next milestone

First Posted

Study publicly available on registry

July 11, 2022

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 30, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2023

Completed
Last Updated

August 11, 2022

Status Verified

August 1, 2022

Enrollment Period

2.5 years

First QC Date

June 23, 2022

Last Update Submit

August 8, 2022

Conditions

Outcome Measures

Primary Outcomes (4)

  • Maternal cardiac function [i.e., global longitudinal (myocardial) strain (GLS) measured by speckle tracking echocardiography (STE)]

    Maternal global longitudinal strain (GLS) measured by speckle tracking echocardiography (STE) will be compared between early pregnancy and postpartum, between pregnant SLE women with and without adverse outcomes, and between SLE and controls in early pregnancy and postpartum stratifying by adverse outcome status. GLS determined by STE will be measured using a 2-D and 3-D STE software (i.e. TomTec Arena). For evaluation of strain, the endocardial border will be traced, at end-systole in the appropriate imaging plane. Peak GLS will be measured by the software using an average of 2 consecutive cardiac cycles. Measures will be repeated twice to calculate intra-observer intraclass correlation coefficient (ICC). Another blinded investigator will review STE assessments to calculate the inter-observer ICC.

    2 years

  • Neonatal cardiac function [i.e., global longitudinal (myocardial) strain (GLS) measured by speckle tracking echocardiography (STE)]

    GLS measured by STE will be compared between children born to mothers with adverse pregnancy outcomes and those born to mothers without adverse pregnancy outcomes, stratifying my maternal SLE status. GLS determined by STE will be measured using a 2-D and 3-D STE software (i.e. TomTec Arena). For evaluation of strain, the endocardial border will be traced, at end-systole in the appropriate imaging plane. Peak GLS will be measured by the software using an average of 2 consecutive cardiac cycles. Measures will be repeated twice to calculate intra-observer intraclass correlation coefficient (ICC). Another blinded investigator will review STE assessments to calculate the inter-observer ICC.

    2 years

  • Maternal autoantibodies and neonatal global longitudinal strain (GLS) in SLE pregnancies

    In SLE offspring, the investigators will determine if GLS differs among those exposed to maternal autoantibodies (assessing respectively anti-Ro/La and aPL) versus unexposed offspring. As well, stratification by quartiles of HCQ cord blood levels will be explored.

    2 years

  • Maternal and cord blood hydroxychloroquine (HCQ) levels with maternal and neonatal global longitudinal strain (GLS)

    Any relationship between GLS and HCQ in maternal and cord blood (e.g., J-curve relationship) will be assessed.

    2 years

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

The At the heart of the matter cohort is a prospective cohort of pregnant women with or without SLE with singleton pregnancies recruited at the Montreal General Hospital and the Royal Victoria Hospital in Montreal, QC, since 2022. This cohort has been established to assess maternal and neonatal myocardial strain in SLE and non-SLE pregnant women, as well as myocardial strain in SLE with or without APOs. This cohort will also be used to study the relationship between HCQ and myocardial strain in SLE mothers and offspring.

You may qualify if:

  • Followed at participating sites;
  • English/French speaking;
  • Gestational age up to 17 weeks
  • Intrauterine singleton pregnancy;
  • Between the ages of 18 and 45 years

You may not qualify if:

  • Women with multiple intrauterine or extrauterine pregnancies;
  • Women with prior history of placenta-mediated pregnancy complication;
  • Women with preexisting cardiovascular disease, hypertension, and non-gestational diabetes

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, SystemicCardiovascular DiseasesPregnancy Complications

Condition Hierarchy (Ancestors)

Connective Tissue DiseasesSkin and Connective Tissue DiseasesAutoimmune DiseasesImmune System DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Central Study Contacts

Évelyne Vinet, MD, PhD

CONTACT

Esther Lee, BSc

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 23, 2022

First Posted

July 11, 2022

Study Start

April 1, 2021

Primary Completion

September 30, 2023

Study Completion

September 30, 2023

Last Updated

August 11, 2022

Record last verified: 2022-08

Locations