Immunosuppressant Regimens for Living Fetuses Study

August 8, 2019 updated by: Liangjing Lu, RenJi Hospital

A Three-arm, Multicenter, Open-label Randomized Controlled Trial of Hydroxychloroquine and Low-dose Prednisone on Recurrent Spontaneous Abortion With Undifferentiated Connective Tissue Diseases: Protocol for the Immunosuppressant Regimens for Living FEtuses (ILIFE) Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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: 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.

Study Type

Interventional

Enrollment (Anticipated)

420

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200001

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live birth rate
Time Frame: After 28 weeks of gestation
Percentage of all cycles that lead to live birth
After 28 weeks of gestation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of miscarriage
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.
Within 28 weeks of gestation
Premature birth
Time Frame: between 28 and 37 weeks of gestations
live birth between 28 and 37 weeks of gestations 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)
between 28 and 37 weeks of gestations
Intrauterine growth retardation
Time Frame: between 28 and 37 weeks of gestations
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)
between 28 and 37 weeks of gestations
Gestational age and weight at birth
Time Frame: post-partum 6 weeks
the children's gestational age and weight at birth
post-partum 6 weeks
Survival at 28 days
Time Frame: post-partum 6 weeks
still alive at 28 days
post-partum 6 weeks
Number of newborns with treatment-related adverse events assessed by 3 parameters
Time Frame: post-partum 6 weeks
assess the number of the newborns with abnormal vision, hearing and length at 6 weeks
post-partum 6 weeks
Congenital abnormality
Time Frame: post-partum 6 weeks
congenital heart conduction block, neonatal lupus or malformation
post-partum 6 weeks
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
After 20 weeks of gestation
Number of participants with Infection
Time Frame: through study completion, an average of 1.5 years
Infection of respiratory tract, digestive tract, urinary tract and skin
through study completion, an average of 1.5 years
Gestational diabetes mellitus
Time Frame: through study completion, an average of 1.5 years
Clinical diagnosis of gestational diabetes mellitus
through study completion, an average of 1.5 years
Activity of UCTD
Time Frame: through study completion, an average of 1.5 years
New onset or aggravation of symptoms like arthritis, rash, Reynolds phenomenon, proteinuria, etc.
through study completion, an average of 1.5 years
Number of participants who evolved to systemic lupus erythematosus(SLE) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of systemic lupus erythematosus
post-partum 6 weeks
Number of participants who evolved to Sjogren's syndrome(SS) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of Sjogren's syndrome
post-partum 6 weeks
Number of participants who evolved to systemic sclerosis(SSc) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of systemic sclerosis
post-partum 6 weeks
Number of participants who evolved to polymyositis(PM) or dermatomyositis(DM) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of polymyositis or dermatomyositis
post-partum 6 weeks
Number of participants who evolved to antiphospholipid syndrome (APS) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of antiphospholipid syndrome
post-partum 6 weeks
Number of participants who evolved to rheumatoid arthritis (RA) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of rheumatoid arthritis
post-partum 6 weeks
Number of participants who evolved to mixed connective tissue disease(MCTD) from undifferentiated connective tissue diseases(UCTD)
Time Frame: post-partum 6 weeks
Clinical diagnosis of mixed connective tissue disease
post-partum 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

RenJi Hospital

Collaborators

The First Affiliated Hospital with Nanjing Medical University
The First Affiliated Hospital of Anhui Medical University
Xiangya Hospital of Central South University
China-Japan Union Hospital, Jilin University
Wuxi No. 2 People's Hospital

Investigators

  • Study Chair: Liangjing Lu, RenJi hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 2, 2019

Primary Completion (Anticipated)

September 1, 2021

Study Completion (Anticipated)

February 1, 2023

Study Registration Dates

First Submitted

August 30, 2018

First Submitted That Met QC Criteria

September 12, 2018

First Posted (Actual)

September 14, 2018

Study Record Updates

Last Update Posted (Actual)

August 12, 2019

Last Update Submitted That Met QC Criteria

August 8, 2019

Last Verified

August 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ILIFE Study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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