Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage

Study Overview
=================
Brief Summary
-----------------
The investigators want to test whether infusions of intravenous immunoglobulin - a blood product known to modify immune responses - in early pregnancy will increase the chance of a subsequent live birth in women with three or more miscarriages after a birth and a total of at least four miscarriages. This will be done in a trial where 82 patients will be randomly allocated to infusions with intravenous immunoglobulin or placebo during pregnancy.

Official Title
-----------------
A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Immunoglobulin for Women With Unexplained Secondary Recurrent Miscarriage

Conditions
-----------------
Secondary Recurrent Miscarriage

Intervention / Treatment
-----------------
* Drug: Intravenous immunoglobulin
* Drug: Human albumin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 4 or more miscarriages before the end of gestational week 14 in patients with secondary recurrent miscarriages. At least three of these must be consecutive after the previous birth At least two of the miscarriages with the present partner. Exclusion Criteria: Age below 18 or above 41 years at conception Significant uterine anomalies detected by hysterosalpingography, hysteroscopy or hydrosonography. Significant chromosomal aberrations in the couple Menstrual cycle < 23 or > 35 days Presence of lupus anticoagulant or IgG anticardiolipin concentration >= 40 GPL ku/l or plasma homocystein >= 25 microg./l by repeated measurements at 8 weeks intervals Tests positive for HIV or tests indicating carriage of hepatitis B or C IgA deficiency Allergy to albumin, IvIg or one of the substances added to preserve the drugs. Presence of chronic disease, which necessitate permanent treatment with e.g. corticosteroids , non-steroidal antiinflammatory drugs, anticoagulation, simvastatin or imurel from the start of pregnancy. Less than 2 of the previous pregnancy losses documented by ultrasound or uterine curettage. Present pregnancy a result of donor insemination or egg donation. Planned administration of gestagens or estrogens from the beginning of pregnancy. 3 or more previous IVF/ICSI/FER attempts resulting in chemical pregnancy/miscarriage. Previous participation in the trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IvIg<br>Repeated infusions of intravenous immunoglobulin in early pregnancy | Drug: Intravenous immunoglobulin<br>* Intravenous infusions, 25-35 g each time, 4th to 15th gestational week<br>* Other names: Intravenous immunoglobulin Privigen CSL Behring 100mg/ml;|
| Placebo Comparator: placebo<br>infusion of human albumin CSL Behring 5% | Drug: Human albumin<br>* Repeated infusions of Human Albumin 5%, 250-350 ml between 4th and 15th gestational week<br>* Other names: Human Albumin 5% CSL Behring;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the subsequent livebirth rate among patients with secondary recurrent miscarriage who, during the trial, receive intravenous immunoglobulin or placebo, respectively, without any exclusions (ITT analysis) |  | August 2008 to June 2011 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference in the subsequent livebirth rate among women with secondary recurrent miscarriage who receive intravenous immunoglobulin or placebo, respectively, after relevant and predefined exclusions (PP analysis). |  | August 2008 to June 2011 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
recurrent miscarriage, immunology, intravenous immunoglobulin, miscarriage