Secondary Recurrent MiscarriagePhase 3NCT00722475
Trial of the Efficacy of Intravenous Immunoglobulin for Treating Women With Unexplained Secondary Recurrent Miscarriage
A Phase 3 study testing Intravenous immunoglobulin and Human albumin in people with Secondary Recurrent Miscarriage, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Secondary Recurrent Miscarriage
- What is being tested?
- Intravenous immunoglobulin and Human albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 1 siteDenmark
- Study dates
- Aug 2008to May 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Immunoglobulin for Women With Unexplained Secondary Recurrent Miscarriage
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.
- Conditions
- Secondary Recurrent Miscarriage
- Being tested
- Intravenous immunoglobulin, Human albumin
- Keywords
- recurrent miscarriage, immunology, intravenous immunoglobulin, miscarriage
- Medical subject headings
- Abortion, Habitual, Abortion, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous immunoglobulinDrug
Also called Intravenous immunoglobulin Privigen CSL Behring 100mg/ml
Intravenous infusions, 25-35 g each time, 4th to 15th gestational week
Human albuminDrug
Also called Human Albumin 5% CSL Behring
Repeated infusions of Human Albumin 5%, 250-350 ml between 4th and 15th gestational week
| Study group | Role | What they receive |
|---|---|---|
| IvIg | Experimental | Repeated infusions of intravenous immunoglobulin in early pregnancy Receives: Drug: Intravenous immunoglobulin |
| placebo | Placebo comparator | infusion of human albumin CSL Behring 5% Receives: Drug: Human albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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).
Measured: August 2008 to June 2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2008 (estimated)
- Study startAug 2008
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Secondary Recurrent MiscarriageStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark
- Responsible party
- Principal investigator, Ole B Christiansen, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Ole B. Christiansen, MD, D.M.Sc., Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00722475
- Sponsor's protocol ID
- IvIg for recurrent miscarriage
- Other IDs
- EudraCT nr. 2008-001589-94
- Status last verified
- Nov 2014
- First submitted
- 23 Jul 2008
- Last updated
- 6 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 17166218Christiansen 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.
PubMed 11870141Christiansen 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.
PubMed 1639992Christiansen 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.
PubMed 8567794Egerup 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.
PubMed 27591241Christiansen 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.
PubMed 25412569
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Placebo-controlled, Double-blind Trial of Intravenous Immunoglobulin for Women With Unexplained Secondary Recurrent Miscarriage
- ClinicalTrials.gov ID
- NCT00722475
- Acronym / sponsor ID
- IvIg for recurrent miscarriage
- Conditions
- Secondary Recurrent Miscarriage
- Keywords
- recurrent miscarriage, immunology, intravenous immunoglobulin, miscarriage
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark
- Study start
- Aug 2008
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 25 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IvIg | Experimental | Drug: Intravenous immunoglobulinRepeated infusions of intravenous immunoglobulin in early pregnancy |
| placebo | Placebo comparator | Drug: Human albumininfusion of human albumin CSL Behring 5% |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous immunoglobulinAlso: Intravenous immunoglobulin Privigen CSL Behring 100mg/mlIntravenous infusions, 25-35 g each time, 4th to 15th gestational week | Drug | IvIg |
| Human albuminAlso: Human Albumin 5% CSL BehringRepeated infusions of Human Albumin 5%, 250-350 ml between 4th and 15th gestational week | Drug | placebo |
Primary outcome
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)
Time frame: August 2008 to June 2011
1 secondary outcome
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).
Time frame: August 2008 to June 2011
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2014.
- Background: PubMed 17166218Hutton 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.
- Background: PubMed 11870141Christiansen 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.
- Background: PubMed 1639992Christiansen 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.
- Background: PubMed 8567794Christiansen 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.
- Derived from this study: PubMed 27591241Egerup 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.
- Derived from this study: PubMed 25412569Christiansen 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ole B. Christiansen, MD, D.M.Sc. principal investigator
Copenhagen University Hospital, Rigshospitalet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Intravenous immunoglobulin and Human albumin in people with Secondary Recurrent Miscarriage, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: August 2008 to June 2011). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00722475, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2014.