The Clinical Features and Pregnancy Outcomes of CTD Patients

Recruiting

• Conditions: Pregnancy Related; Connective Tissue Diseases
• Interventions: Drug: Prednisone; Drug: Hydroxychloroquine; Drug: Aspirin; Drug: low molecular weight heparin Enoxaparin

• Registration Number: NCT04918524
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

Connective tissue disease (CTD) is a common group of autoimmune diseases, mainly including systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) , and so on. APS is caused by autoimmune disorders that cause recurrent miscarriage, thrombosis, and thrombocytopenia, and often secondary to connective tissue diseases such as SLE. Undifferentiated connective tissue disease (UCTD) is currently considered to be an independent disease in the classification of CTD. And women of childbearing age who suffer UCTD is more common than that in other definite CTDs. Therefore, the impact of the disease flare and the influence of medicine on pregnancy and lactation are important for these patients who may suffer high-risk of abnormal pregnance.

Detailed Description

Objective: To study the risk factors of poor pregnancy outcomes in CTD patients, and evaluate impact of different therapies on the maternal and fetal health.

Methods: Our department and Shanghai Gothic Network Technology Co.Ltd. jointly established the chronic disease management of CTD patients during pregnancy and lactation by using Smart System of Disease Management (SSDM). With this platform, patients in pregnancy can consult with rheumatologists face to face and follow-up regularly.

Follow-up: Consultation and followup will be scheduled every 4 weeks from confirmed pregnancy until delivery.

Study Timeline

• Study Start: 2018-09-11
• Study First Submitted: 2021-06-02
• Study First Submitted QC: 2021-06-02
• Study First Posted: 2021-06-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-16
• Last Update Posted: 2023-11-18
• Primary Completion: 2025-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 126

Inclusion Criteria

• Women who meet the following inclusion criteria will be eligible to participate in the study:

  1. Age between 20-45 years;
  2. Diagnosed with APS: patients meet the Sydney classification criteria;
  3. Diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibody(aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting connective tissue disease(CTD) , while not fulfilling any classification criteria of a defined CTD.
  4. Participate voluntarily in this study, willing to use medication and follow-up according to treatment plan, and sign informed consent.

Exclusion Criteria

• Women who meet any of the following criteria will be excluded from the study:

  1.Any known etiology of previous pregnancy loss:

  1. Known paternal, maternal or embryo chromosome abnormality.

  2. Maternal endocrine dysfunction: corpus luteal insufficiency; polycystic ovarian syndrome; premature ovarian failure (follicle stimulating hormone, FSH ≥20uU/L in follicular phase);

  3. hyperprolactinemia; diabetes mellitus; other hypothalamic pituitary-adrenal axis abnormality

  4. Maternal anatomical abnormality: uterine malformation; Asherman syndrome; cervical incompetence; uterine fibrosis more than 5 cm.Vaginal infection.

  5. Any known severe cardiac, hepatic, renal, hematological or endocrinal diseases:

  6. Any active infection: Active infection including V aricella zostervirus(VZV), human immunodeficiency virus (HIV), Human papillomavirus (HPV),syphilis or tuberculosis.

  7. Allergic to prednisone, hydroxychloroquine, low-molecular-weight heparin or aspirin.

  4.Disease history as follows:

  1. Past history of digestive ulcers or upper gastrointestinal hemorrhage.
  2. Past history of malignancy.
  3. Past history of epilepsia or psychotic disorders.

  5.Women have been diagnosed with Systemic lupus erythematosus

  6. Women who disagree or cannot complete pregnancy and follow-up after delivery.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
The Antiphospholipid syndrome (APS)	Prednisone	The cohort includes that patients who meet the proposed Sydney criteria.
The Antiphospholipid syndrome (APS)	low molecular weight heparin Enoxaparin	The cohort includes that patients who meet the proposed Sydney criteria.
Undifferentiated connective tissue disease (UCTD)	low molecular weight heparin Enoxaparin	The cohort includes the patients who are diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibodies (aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting CTD ,while not fulfilling any classification criteria of a defined CTD.
The Antiphospholipid syndrome (APS)	Hydroxychloroquine	The cohort includes that patients who meet the proposed Sydney criteria.
The Antiphospholipid syndrome (APS)	Aspirin	The cohort includes that patients who meet the proposed Sydney criteria.
Undifferentiated connective tissue disease (UCTD)	Prednisone	The cohort includes the patients who are diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibodies (aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting CTD ,while not fulfilling any classification criteria of a defined CTD.
Undifferentiated connective tissue disease (UCTD)	Hydroxychloroquine	The cohort includes the patients who are diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibodies (aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting CTD ,while not fulfilling any classification criteria of a defined CTD.
Undifferentiated connective tissue disease (UCTD)	Aspirin	The cohort includes the patients who are diagnosed with UCTD: at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-extractable nuclear antigen (ENA) antibodies, anti-doublestranded DNA (ds-DNA) antibody, antiphospholipid antibodies (aPL), and non-criteria aPL (NC-aPL), with at least one symptoms or signs suggesting CTD ,while not fulfilling any classification criteria of a defined CTD.

Primary Outcome Measures

Name	Time	Method
Live birth rate	After 28 weeks of gestation	Percentage of all patients that lead to live birth after 28 weeks of gestation

Secondary Outcome Measures

Name	Time	Method
Early fetal loss	within 10 weeks of gestation	Spontaneous pregnancy loss within 10 weeks of gestation
Late fetal loss	after 10 weeks of gestation	Spontaneous pregnancy loss after 10 weeks of gestation
Low-weight birth	after 28 weeks of gestation	newborns with low weight (\<2500g)
Fetal growth retardation (FGR)	after 12 weeks of gestation	weight below the 10th percentile for the gestational age
Number of participants with placental hematoma during pregnancy	during pregnancy, an average of 10 months	the number of participants whose B-ultrasound indicates placental hematoma during pregnancy
Gestational diabetes	through study completion, an average of 10 months	the number of participants who were diagnosed with gestational diabetes
Stillbirth	after 20 weeks of gestation	Spontaneous pregnancy loss after 20 weeks of gestation
Placental abruption	after 28 weeks of gestation	the number of participants complicated with placental abruption
Number of participants with low amniotic fluid during pregnancy	after 12 weeks of gestation	the number of participants whose B-ultrasound indicates low amniotic fluid during pregnancy
Number of participants with abnormal S / D values during pregnancy	after 12 weeks of gestation	the number of participants whose B-ultrasound indicates abnormal S / D values during pregnancy
Eclampsia	after 20 weeks of gestation	New-onset hypertension after 20 weeks of gestation, with or without proteinuria \> 300mg/24h, with or without any organ damage with seizures
Preterm delivery	between 28 and 37 weeks of gestation	Live birth before 37 weeks of gestation
Premature rupture of membranes	after 28 weeks of gestation	the number of participants complicated with premature rupture of membranes
Number of participants with placental infarction	at delivery	the number of participants whose placenta with infarction.
Gestational hypertension	through study completion, an average of 10 months	the number of participants who were diagnosed with gestational hypertension

Trial Locations

Locations (1)

Qilu Hospital; 🇨🇳 Jinan, Shandong, China