Immunosuppressant Regimens for Living Fetuses Study

Shanghai Jiao Tong University

Status: Unknown

Conditions: Undifferentiated Connective Tissue Disease; Recurrent Pregnancy Loss

Treatments: Drug: low molecular weight heparin; Drug: Prednisone; Drug: Aspirin; Drug: Hydroxychloroquine

Study type: Interventional

Funder types: Other

Identifiers

NCT03671174

ILIFE Study

Details and patient eligibility

About

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.

Full 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: 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.

Enrollment: 420 estimated patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria

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

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.
5. Providing written 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. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

420 participants in 3 patient groups

Prednisone + hydroxychloroquine + anticoagulation

Experimental group

Description:

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

Treatment:

Drug: Aspirin

Drug: Prednisone

Drug: Hydroxychloroquine

Drug: low molecular weight heparin

Hydroxychloroquine + anticoagulation

Experimental group

Description:

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

Treatment:

Drug: Aspirin

Drug: Hydroxychloroquine

Drug: low molecular weight heparin

Anticoagulation

Active Comparator group

Description:

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

Treatment:

Drug: Aspirin

Drug: low molecular weight heparin