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Immunosuppressant Regimens for Living Fetuses Study

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ClinicalTrials.gov Identifier: NCT03671174
Recruitment Status : Not yet recruiting
First Posted : September 14, 2018
Last Update Posted : September 14, 2018
Sponsor:
Collaborators:
The First Affiliated Hospital of Anhui Medical University
China-Japan Union Hospital, Jilin University
Wuxi No. 2 People's Hospital
Xiangya Hospital of Central South University
Information provided by (Responsible Party):
Liangjing Lv, RenJi Hospital

Brief Summary:
Undifferentiated connective tissue diseases (UCTD) are known to increase the risk of pregnancy morbidities, including recurrent pregnancy loss. However, there is no consensus or guideline about the treatment for recurrent pregnancy loss in UCTD patients. Therefore, based on the tendency to thrombosis formation and placental inflammation in the pathogenesis of UCTD, this trial proposes to evaluate the effect of hydroxychloroquine with or without prednisone combined with anticoagulation on pregnancy outcomes in recurrent pregnancy loss patients with UCTD.

Condition or disease Intervention/treatment Phase
Undifferentiated Connective Tissue Disease Recurrent Pregnancy Loss Drug: Prednisone Drug: Hydroxychloroquine Drug: Aspirin Drug: low molecular weight heparin Not Applicable

Detailed Description:

Objective: To evaluate the effect of anticoagulation with or without immunomodulatory therapy on pregnancy outcomes of recurrent pregnancy loss with undifferentiated connective tissue diseases Design: a multi-center, randomised, open-label, paralleled study. Patients: Pregnant patients with recurrent pregnancy loss and undifferentiated connective tissue diseases without any known etiology for pregnancy loss (detailed in section 10).

Methods: 375 selected patients are divided into 3 parallel groups (detailed in section 8).

Randomization: Patients who present to relevant clinics for management of recurrent pregnancy loss (RPL) will be evaluated for inclusion criteria and exclusion criteria by a formed physician. Once patient is eligible for the study, the co-investigator will obtain written patient's consent. Participants will be randomized into one of the 3 groups. Randomized numbers will be generated by pharmacology research personnel in Renji Hospital. Given the different administrated medications, neither the patient nor the provider will be blinded.

Follow-up: Consultation will be scheduled every 4 weeks from confirmed pregnancy until delivery. The co-investigator will complete a follow-up survey including clinical, biological data.

Missing data: Patients are willing to drop the study, unavailable, incompliant, with severe complications or with severe adverse effects. The missing data will be recorded in detail and be analysed with last pregnancy outcome.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 375 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Open-label Randomized Controlled Trial of the Effectiveness of Hydroxychloroquine and Low-dose Prednisone Jointed With Anticoagulation and Antiaggregation on Recurrent Spontaneous Pregnancy Loss With Undifferentiated Connective Tissue Diseases: Immunosuppressant Regimens for Living Fetuses Study (ILIFE Trial)
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Prednisone + hydroxychloroquine + anticoagulation
Oral low-dose prednisone PLUS Oral hydroxychloroquine PLUS Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin
Drug: Prednisone
10mg once daily orally

Drug: Hydroxychloroquine
100mg to 200mg twice daily orally

Drug: Aspirin
50mg once daily orally

Drug: low molecular weight heparin
Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous
Other Names:
  • Enoxaparin
  • Dalteparin
  • Nadroparin

Experimental: Hydroxychloroquine + anticoagulation
Oral hydroxychloroquine PLUS Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin
Drug: Hydroxychloroquine
100mg to 200mg twice daily orally

Drug: Aspirin
50mg once daily orally

Drug: low molecular weight heparin
Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous
Other Names:
  • Enoxaparin
  • Dalteparin
  • Nadroparin

Active Comparator: Anticoagulation
Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin
Drug: Aspirin
50mg once daily orally

Drug: low molecular weight heparin
Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous
Other Names:
  • Enoxaparin
  • Dalteparin
  • Nadroparin




Primary Outcome Measures :
  1. Spontaneous pregnancy loss [ Time Frame: Within 28 weeks of gestation ]
    Spontaneous pregnancy loss within 28 weeks of gestation, confirmed by pelvic ultrasound findings. This includes no yolk sac or embryo in a gestational sac and an embryo without cardiac activity.


Secondary Outcome Measures :
  1. Live birth rate [ Time Frame: After 28 weeks of gestation ]
    Percentage of all cycles that lead to live birth

  2. Fetus growth restriction [ Time Frame: After 20 weeks of gestation ]
    Birth weight below the 10th percentile for the gestational age Prematurity (live birth between 28 and 37 weeks of gestations); Eclampsia (new-onset hypertension after 20 weeks of gestation, +/- proteinuria > 300mg/24h, with or without any organ damage with seizures); Fetal abnormality (congenital heart conduction block, neonatal lupus or malformation)

  3. Eclampsia [ Time Frame: 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

  4. Fetal abnormality [ Time Frame: After 28 weeks of gestation ]
    Congenital heart conduction block, neonatal lupus or malformation

  5. Prematurity [ Time Frame: After 28 weeks of gestation ]
    Live birth between 28 and 37 weeks of gestations

  6. UCTD outcomes - evolution to SLE [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to systemic lupus erythematosus (SLE), which means patients confirming the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria.

  7. UCTD outcomes - evolution to APS [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to antiphospholipid antibody syndrome (APS), which means patients confirming the 2006 Sydney criteria for diagnosing APS.

  8. UCTD outcomes - evolution to SS [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to Sjögren's syndrome (SS), which means patients confirming 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for diagnosing SS.

  9. UCTD outcomes - evolution to SSc [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to systemic sclerosis (SSc), which means patients confirming 2013 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for diagnosing SSc.

  10. UCTD outcomes - evolution to DM/PM [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to dermatomyositis/polymyositis (DM/PM), which means patients confirming 2017 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for diagnosing DM or PM

  11. UCTD outcomes - evolution to RA [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to rheumatoid arthritis (RA), which means patients confirming 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for diagnosing RA.

  12. UCTD outcomes - evolution to AS [ Time Frame: Through study, average 1 year ]
    Whether UCTD evolute to ankylosing spondylitis (AS), which means patients confirming 2009 and 2011 Assessment of SpondyloArthritis International Society (ASAS) criteria for diagnosing AS.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of undifferentiated connective tissue diseases [at least one symptoms or signs suggesting connective tissue disease (CTD) and with at least one presence of auto-antibodies, including antinuclear antibodies (ANA), anti-SSA antibodies (anti-SSA), while not fulfilling any classification criteria of a defined CTD] with recurrent pregnancy loss (at least two consecutive spontaneous pregnancy loss )
  2. Female of reproductive age (20-40 years old)
  3. Obtained fully informed patients' consents

Exclusion Criteria:

  1. Any known etiology of pregnancy loss:

    • Diagnosis of antiphospholipid antibody syndrome
    • Known paternal, maternal or embryo chromosome abnormality
    • Maternal endocrine dysfunction: corpus luteal insufficiency; polycystic ovarian syndrome; premature ovarian failure (FSH ≥20uU/L in follicular phase); hyperprolactinemia; thyroid disease; diabetes mellitus; other hypothalamic-pituitary-adrenal axis abnormality;
    • Maternal anatomical abnormality: uterine malformation; Asherman syndrome; cervical incompetence; uterine fibrosis more than 5 cm;
    • Vaginal infection;
  2. Any known severe cardiac, hepatic, renal, hematological or endocrinal diseases:

    • alanine transaminase (ALT) or aspartate transaminase (AST) more than twice the Upper Limit of Normal;
    • Clearance of creatinine less than 30mL/min;
    • Leucocytes less than 2.5*10^9/L;
    • Hemoglobins less than 85g/L;
    • Platelets less than 50*10^9/L
  3. Any active viral hepatitis or history of severe viral hepatitis, including Hepatitis B Virus (HBV), Hepatitis C Virus (HCV);
  4. Allergic to prednisone, hydroxychloroquine, low-molecular-weight heparin or aspirin
  5. Any active infection , including varicellae-zona virus (VZV), human immunodeficiency virus (HIV) or tuberculosis
  6. History of digestive ulcers or upper gastrointestinal hemorrhage
  7. History of malignancy
  8. Any psychiatric diseases
  9. History of seizures or other neurology dysfunction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03671174


Contacts
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Contact: Liangjing LV +86 13661472001 Lu_liangjing@163.com

Sponsors and Collaborators
RenJi Hospital
The First Affiliated Hospital of Anhui Medical University
China-Japan Union Hospital, Jilin University
Wuxi No. 2 People's Hospital
Xiangya Hospital of Central South University
Investigators
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Study Chair: Liangjing LV RenJi Hospital

Publications of Results:

Other Publications:
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Responsible Party: Liangjing Lv, Professor, RenJi Hospital
ClinicalTrials.gov Identifier: NCT03671174     History of Changes
Other Study ID Numbers: ILIFE Study
First Posted: September 14, 2018    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: No

Additional relevant MeSH terms:
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Anticoagulants
Connective Tissue Diseases
Abortion, Spontaneous
Fetal Death
Abortion, Habitual
Undifferentiated Connective Tissue Diseases
Pregnancy Complications
Death
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Prednisone
Aspirin
Heparin
Calcium heparin
Heparin, Low-Molecular-Weight
Dalteparin
Nadroparin
Hydroxychloroquine
Immunosuppressive Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics