Immunosuppressant Regimens for Living Fetuses Study

NCT ID: NCT03671174

Last Updated: 2019-08-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-08-02

Study Completion Date

2023-02-28

Brief Summary

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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.

Detailed Description

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

Randomization: Patients who present to relevant clinics for management of recurrent spontaneous abortion (RSA) 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.

Conditions

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Undifferentiated Connective Tissue Disease Recurrent Pregnancy Loss

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Prednisone + hydroxychloroquine + anticoagulation

Oral low-dose prednisone PLUS Oral hydroxychloroquine PLUS Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin

Group Type EXPERIMENTAL

Prednisone

Intervention Type DRUG

10mg once daily orally

Hydroxychloroquine

Intervention Type DRUG

100mg to 200mg twice daily orally

Aspirin

Intervention Type DRUG

50mg once daily orally

low molecular weight heparin

Intervention Type DRUG

Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous

Hydroxychloroquine + anticoagulation

Oral hydroxychloroquine PLUS Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin

Group Type EXPERIMENTAL

Hydroxychloroquine

Intervention Type DRUG

100mg to 200mg twice daily orally

Aspirin

Intervention Type DRUG

50mg once daily orally

low molecular weight heparin

Intervention Type DRUG

Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous

Anticoagulation

Oral low-dose aspirin PLUS subcutaneous low-molecular-weight heparin

Group Type ACTIVE_COMPARATOR

Aspirin

Intervention Type DRUG

50mg once daily orally

low molecular weight heparin

Intervention Type DRUG

Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous

Interventions

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Prednisone

10mg once daily orally

Intervention Type DRUG

Hydroxychloroquine

100mg to 200mg twice daily orally

Intervention Type DRUG

Aspirin

50mg once daily orally

Intervention Type DRUG

low molecular weight heparin

Enoxaparin 40mg once daily subcutaneous or dalteparin 5000IU once daily subcutaneous or nadroparin calcium 4100U once daily subcutaneous

Intervention Type DRUG

Other Intervention Names

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Enoxaparin Dalteparin Nadroparin

Eligibility Criteria

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Inclusion Criteria

1. At reproductive age (20-40 years old).
2. Trying to conceive.
3. Diagnosed with UCTD\[2\]: at least one symptoms or signs suggesting connective tissue disease(CTD) and with at least one presence of auto-antibodies, including antinuclear antibody (ANA), anti-SSA antibody, while not fulfilling any classification criteria of a defined CTD.
4. Diagnosed with RSA\[39\]: two or more failed pregnancies of unknown origin.

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

(1)Alanine transaminase (ALT) or aspartate transaminase(AST) more than twice the upper limit of normal.

(2)Clearance of creatinine less than 30mL/min. (3)Leucocytes less than 2.5\*10\^9/L, or Hemoglobine less than 85g/L, or Platelet less than 50\~10\^9/L.

3.Any active infection:

1. Active viral hepatitis including hepatitis B virus (HBV), hepatitis C virus (HCV).
2. Active infection including V aricella-zostervirus(VZV), human immunodeficiency virus (HIV), syphilis or tuberculosis.

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

5.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. 6.Woman unable to consent or impossible to follow-up.
Minimum Eligible Age

20 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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The First Affiliated Hospital of Anhui Medical University

OTHER

Sponsor Role collaborator

China-Japan Union Hospital, Jilin University

OTHER

Sponsor Role collaborator

Wuxi No. 2 People's Hospital

OTHER

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role collaborator

RenJi Hospital

OTHER

Sponsor Role lead

Responsible Party

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Liangjing Lu

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Liangjing Lu

Role: STUDY_CHAIR

RenJi Hospital

Locations

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Renji Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Liangjing Lu

Role: CONTACT

+86 13661472001

Facility Contacts

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Liangjing Lu

Role: primary

+8613661472001

Shaoying Yang

Role: backup

+8613601984013

References

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Reference Type DERIVED
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Other Identifiers

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ILIFE Study

Identifier Type: -

Identifier Source: org_study_id

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