NCT00722475

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
82

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Aug 2008

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 23, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 25, 2008

Completed
7 days until next milestone

Study Start

First participant enrolled

August 1, 2008

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

November 6, 2014

Status Verified

November 1, 2014

Enrollment Period

5.8 years

First QC Date

July 23, 2008

Last Update Submit

November 5, 2014

Conditions

Secondary Recurrent Miscarriage

Keywords

recurrent miscarriageimmunologyintravenous immunoglobulinmiscarriage

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • 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

Study Arms (2)

IvIg

EXPERIMENTAL

Repeated infusions of intravenous immunoglobulin in early pregnancy

Drug: Intravenous immunoglobulin

placebo

PLACEBO COMPARATOR

infusion of human albumin CSL Behring 5%

Drug: Human albumin

Interventions

Intravenous immunoglobulinDRUG

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

Also known as: Intravenous immunoglobulin Privigen CSL Behring 100mg/ml
IvIg
Human albuminDRUG

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

Also known as: Human Albumin 5% CSL Behring
placebo

Eligibility Criteria

Age18 Years - 40 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • or more previous IVF/ICSI/FER attempts resulting in chemical pregnancy/miscarriage.
  • Previous participation in the trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Fertility Clinic 4071, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Related Publications (6)

  • 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.

    PMID: 17166218BACKGROUND

  • 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.

    PMID: 11870141BACKGROUND

  • 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.

    PMID: 1639992BACKGROUND

  • 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.

    PMID: 8567794BACKGROUND

  • 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.

    PMID: 27591241DERIVED

  • 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.

    PMID: 25412569DERIVED

MeSH Terms

Conditions

Abortion, HabitualAbortion, Spontaneous

Interventions

Immunoglobulins, IntravenousSerum Albumin, Human

Condition Hierarchy (Ancestors)

Pregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin GImmunoglobulin IsotypesAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsSerum AlbuminAlbumins

Study Officials

  • Ole B. Christiansen, MD, D.M.Sc.

    Rigshospitalet, Denmark

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
consultant

Study Record Dates

First Submitted

July 23, 2008

First Posted

July 25, 2008

Study Start

August 1, 2008

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

November 6, 2014

Record last verified: 2014-11

Locations

DK(1)