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

Primary Purpose

Secondary Recurrent Miscarriage

Status

Completed

Phase

Phase 3

Locations

Denmark

Study Type

Interventional

Intervention

Intravenous immunoglobulin

Human albumin

About this trial

This is an interventional treatment trial for Secondary Recurrent Miscarriage focused on measuring recurrent miscarriage, immunology, intravenous immunoglobulin, miscarriage

Eligibility Criteria

18 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Fertility Clinic 4071, Rigshospitalet

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IvIg

placebo

Arm Description

Repeated infusions of intravenous immunoglobulin in early pregnancy

infusion of human albumin CSL Behring 5%

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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).

Full Information

NCT ID

NCT00722475

First Posted

July 23, 2008

Last Updated

November 5, 2014

Sponsor

Rigshospitalet, Denmark

Collaborators

The Ministry of Science, Technology and Innovation, Denmark

1. Study Identification

Unique Protocol Identification Number

NCT00722475

Brief Title

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

2. Study Status

Record Verification Date

November 2014

Overall Recruitment Status

Completed

Study Start Date

August 2008 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Rigshospitalet, Denmark

Collaborators

The Ministry of Science, Technology and Innovation, Denmark

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Secondary Recurrent Miscarriage

Keywords

recurrent miscarriage, immunology, intravenous immunoglobulin, miscarriage

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

82 (Actual)

8. Arms, Groups, and Interventions

Arm Title

IvIg

Arm Type

Experimental

Arm Description

Repeated infusions of intravenous immunoglobulin in early pregnancy

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

infusion of human albumin CSL Behring 5%

Intervention Type

Drug

Intervention Name(s)

Intravenous immunoglobulin

Other Intervention Name(s)

Intravenous immunoglobulin Privigen CSL Behring 100mg/ml

Intervention Description

Intravenous infusions, 25-35 g each time, 4th to 15th gestational week

Intervention Type

Drug

Intervention Name(s)

Human albumin

Other Intervention Name(s)

Human Albumin 5% CSL Behring

Intervention Description

Repeated infusions of Human Albumin 5%, 250-350 ml between 4th and 15th gestational week

Primary Outcome Measure Information:

Title

Time Frame

August 2008 to June 2011

Secondary Outcome Measure Information:

Title

Time Frame

August 2008 to June 2011

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ole B. Christiansen, MD, D.M.Sc.

Organizational Affiliation

Rigshospitalet, Denmark

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fertility Clinic 4071, Rigshospitalet

City

Copenhagen

ZIP/Postal Code

DK-2100

Country

Denmark

12. IPD Sharing Statement

Citations:

PubMed Identifier

17166218

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.

Results Reference

background

PubMed Identifier

11870141

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.

Results Reference

background

PubMed Identifier

1639992

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.

Results Reference

background

PubMed Identifier

8567794

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.

Results Reference

background

PubMed Identifier

27591241

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.

Results Reference

derived

PubMed Identifier

25412569

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.

Results Reference

derived

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

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