Clinical trial NCT00722475: Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage
Official title: A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Immunoglobulin for Women With Unexplained Secondary Recurrent Miscarriage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Secondary Recurrent Miscarriage
Keywords: recurrent miscarriage
immunology
intravenous immunoglobulin
miscarriage
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: The Ministry of Science, Technology and Innovation, Denmark
First posted: 2008-07-25
Enrollment: 82
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: 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)
timeFrame: August 2008 to June 2011
Secondary outcomes:
measure: 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).
timeFrame: August 2008 to June 2011
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Fertility Clinic 4071, Rigshospitalet
Study officials:
affiliation: Rigshospitalet, Denmark
name: Ole B. Christiansen, MD, D.M.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hutton B, Sharma R, Fergusson D, Tinmouth A, Hebert P, Jamieson J, Walker M. Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review. BJOG. 2007 Feb;114(2):134-42. doi: 10.1111/j.1471-0528.2006.01201.x. Epub 2006 Dec 12.
citation: Christiansen OB, Pedersen B, Rosgaard A, Husth M. A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage. Hum Reprod. 2002 Mar;17(3):809-16. doi: 10.1093/humrep/17.3.809.
citation: Christiansen OB, Mathiesen O, Lauritsen JG, Grunnet N. Intravenous immunoglobulin treatment of women with multiple miscarriages. Hum Reprod. 1992 May;7(5):718-22. doi: 10.1093/oxfordjournals.humrep.a137724.
citation: Christiansen OB, Mathiesen O, Husth M, Rasmussen KL, Ingerslev HJ, Lauritsen JG, Grunnet N. Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin. Hum Reprod. 1995 Oct;10(10):2690-5. doi: 10.1093/oxfordjournals.humrep.a135769.
citation: Egerup P, Kolte AM, Larsen EC, Krog M, Nielsen HS, Christiansen OB. Recurrent pregnancy loss: what is the impact of consecutive versus non-consecutive losses? Hum Reprod. 2016 Nov;31(11):2428-2434. doi: 10.1093/humrep/dew169. Epub 2016 Sep 2.
citation: Christiansen OB, Larsen EC, Egerup P, Lunoee L, Egestad L, Nielsen HS. Intravenous immunoglobulin treatment for secondary recurrent miscarriage: a randomised, double-blind, placebo-controlled trial. BJOG. 2015 Mar;122(4):500-8. doi: 10.1111/1471-0528.13192. Epub 2014 Nov 21.