UMIN-CTR Clinical Trial

Public title

Effect of intravenous immunoglobulin (IVIG) in pregnant women with refractory obstetric antiphospholipid syndrome: A prospective single-arm interventional study

Acronym

Effect of intravenous immunoglobulin (IVIG) in pregnant women with refractory obstetric antiphospholipid syndrome: A prospective single-arm interventional study

Scientific Title

Effect of intravenous immunoglobulin (IVIG) in pregnant women with refractory obstetric antiphospholipid syndrome: A prospective single-arm interventional study

Scientific Title:Acronym

Effect of intravenous immunoglobulin (IVIG) in pregnant women with refractory obstetric antiphospholipid syndrome: A prospective single-arm interventional study

Region

Japan

Condition

antiphospholipid syndrome

Classification by specialty

Clinical immunology

Obstetrics and Gynecology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Obstetric antiphospholipid syndrome (APS) is characterized by recurrent early miscarriages, fetal loss in later pregnancy, and maternal thrombosis. Although the first-line treatment regimen for women with obstetric APS is anticoagulation therapy consisting of a combination of heparin and low dose aspirin (LDA), 20-30% of cases result in pregnancy failure despite appropriate treatment. In addition, these patients are at a significantly higher risk of developing recurrent severe gestational complications such as maternal thrombosis, preeclampsia, and the HELLP syndrome.
Adding immunosuppressive therapies to standard antithrombotic therapy for refractory APS patients has been anticipated. IVIg may be a good candidate treatment for refractory obstetric APS; several reports have described the efficacy of IVIg therapy in women with refractory APS.
Our objective in this study is to determine the efficacy of IVIg therapy for refractory obstetric APS.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Live birth rate after 30 weeks of gestation

Key secondary outcomes

1 Comparison of pregnancy outcomes (including birth outcomes) between previous pregnancies and the current pregnancy with the intervention (efficacy)
2 Assessment of the prevalence of pregnancy complications (gestational hypertension, preeclampsia, HELLP syndrome, placental abruption, and fetal growth restriction [FGR]) (efficacy)
3 Changes in antiphospholipid antibody titers (aCL IgG/IgM, aCL&beta2GP-I IgG, LA) (efficacy)
4 All adverse events, including laboratory test results during pregnancy and the postpartum period (safety)

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Historical

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Intravenous immunoglobulin administration (IVIG) during early pregnancy, in addition to standard anticoagulation therapy.
A five-day course of IVIG (400 mg/kg body weight) was initiated soon after confirmation of a fetal heartbeat (FHB).

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

Pregnant women with APS diagnosed according to the international criteria who meet the following inclusion criteria will be enrolled:
1. One or more unexplained episodes of fetal death of a morphologically normal fetus at or beyond the 10th week of gestation, an episode of fetal death without fetal chromosomal abnormalities at or beyond the 10th week of gestation, or an episode of preterm delivery before the 30th week of gestation due to pregnancy complications (e.g., severe preeclampsia or gestational hypertension, FGR, or placental abruption) despite standard anticoagulation therapy.
2. A history of vascular thrombosis due to pregnancy despite standard anticoagulation therapy.

Key exclusion criteria

1 History of drug hypersensitivity
2 History of heparin-induced thrombocytopenia
3 Hereditary fructose intolerance
4 IgA deficiency
5 Uterine anomalies, uterine submucosal myomas, or intrauterine tumors more than 10 cm in diameter
6 Inability to obtain written informed consent
7 Abnormal laboratory blood test results:
Platelets are less than 50000/mm3
ALT, ALT, LDH, and ganma-GTP are more than 1.5 times the upper limit at each institution
Plasma creatinine is more than 0.8 mg/dl

Target sample size

8

Name of lead principal investigator

1st name	Atsuko
Middle name
Last name	Murashima

Organization

National Center for Child Health and Development

Division name

Center of Maternal-Fetal, Neonatal and Reproductive Medicine

Zip code

1578535

Address

2-10-1, Okura Setagaya, Tokyo, Japan

TEL

0334160181

Email

kaneko-ky@ncchd.go.jp

Name of contact person

1st name	Kayoko
Middle name
Last name	Kaneko

Organization

National center for Child health and Development

Division name

Division of Maternal Medicine, Center of Maternal-Fetal, Neonatal and Reproductive Medicine

Zip code

1578535

Address

2-10-1, Okura, setagaya-ku

TEL

0334160181

Homepage URL

Email

kaneko-ky@ncchd.go.jp

Institute

National Center for Child Health and Development

Institute

Department

Personal name

Organization

Health Labour Sciences Research Grant, Diagnosis and treatment of antiphospholipid syndrome in obstetric field

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

Certified Clinical Research Review Board, National Center for Child Health and Development

Address

2-10-1, Okura, setagaya-ku

Tel

0334160181

Email

rinken@ncchd.go.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

国立成育医療研究センター病院（東京都）、大阪府立母子保健総合医療センター（大阪府）、愛媛大学医学部付属病院（愛媛県）、北里メディカルセンター（埼玉県）、大阪医科薬科大学（大阪府)

Date of disclosure of the study information

2014

Year

03

Month

25

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

8

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

06

Month

14

Day

Date of IRB

2014

Year

02

Month

10

Day

Anticipated trial start date

2016

Year

06

Month

14

Day

Last follow-up date

2023

Year

03

Month

31

Day

Date of closure to data entry

2023

Year

03

Month

31

Day

Date trial data considered complete

2023

Year

03

Month

31

Day

Date analysis concluded

2023

Year

03

Month

31

Day

Other related information

Registered date

2014

Year

03

Month

24

Day

Last modified on

2023

Year

03

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015764