Abortion, Habitual, Miscarriage, Recurrent
Conditions
Keywords
Recurrent miscarriage, Recurrent spontaneous abortion, Habitual abortion, IVIG, Randomized Controlled Trial
Brief summary
Recurrent miscarriage is a prevalent reproductive problem that affects many couples who are trying to establish a family. This clinical study will evaluate the effectiveness of intravenous immunoglobulin (IVIG) in improving the live birth rate in couples who suffer from secondary recurrent miscarriage. This study will help in providing an answer to the question of whether IVIG is helpful in secondary recurrent miscarriage.
Detailed description
The purpose of this multi-center trial is to evaluate the efficacy of IVIG in improving the ongoing pregnancy (\>20 weeks of gestation) rate in couples with unexplained secondary recurrent miscarriage, and; to characterize and compare pharmacokinetic and pharmacodynamic parameters for IVIG pre-conceptually and in the 1st and 2nd trimesters of pregnancy, so that an improved IVIG dosing strategy can be determined.
Interventions
BIOLOGICALGamimune N or Gamunex 10%
500 mg/kg administered in the follicular phase of the menstrual cycle. With conception, infusions every four weeks until 18-20 weeks of gestation.
OTHERnormal saline
equivalent volume of normal saline
Sponsors
University of British Columbia
University of Tennessee
Sunnybrook Health Sciences Centre
Grifols Therapeutics LLC
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
* Couple has a history of unexplained secondary recurrent miscarriage. * Most recent pregnancy occurred within one year of discontinuing contraception.
Exclusion criteria
* Maternal IgA deficiency * Maternal history of immunoglobulin hypersensitivity. * Maternal contraindication to pregnancy. * Evidence of active hepatitis or immunocompromised state in either partner. * Concomitant use of medication(s) for treatment of recurrent miscarriage, such as but not limited to progesterone, clomiphene citrate, acetylsalicylic acid, heparin, glucocorticoids or hCG injections.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Successful Pregnancies Defined as an Ongoing Pregnancy Over 20 Weeks Gestation, Per Number of Index Pregnancies | 20 weeks gestation |
Countries
United States
Participant flow
Recruitment details
Between November 1999 and February 2008, a total of 82 women were recruited from seven centers: University of British Columbia, University of Chicago, University of Tennessee-Memphis, University of Toronto, Ottawa University, Yale University and McMaster University.
Pre-assignment details
Five of the 82 withdrew consent prior to group assignment.
Participants by arm
| Arm | Count |
|---|---|
| IVIG IVIG, either Gamimune N (Talecris Biotherapeutics, Inc., Clayton, NC) or Gamunex 10% (Talecris Biotherapeutics, Inc., Clayton, NC), both as a 10% solution. 500 mg/kg adminstered in the follicular phase of the menstrual cycle. With conception, infusions every four weeks until 18-20 weeks of gestation. | 23 |
| Normal Saline equivalent volume of normal saline | 24 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Non-Index Pregnancy | 1 | 4 |
| Overall Study | No Pregnancy | 9 | 6 |
| Overall Study | Withdrew | 5 | 5 |
Baseline characteristics
| Characteristic | IVIG | Normal Saline | Total |
|---|---|---|---|
| Age Continuous | 36 years STANDARD_DEVIATION 5 | 35 years STANDARD_DEVIATION 4 | 36 years STANDARD_DEVIATION 4 |
| Sex: Female, Male Female | 23 Participants | 24 Participants | 47 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 23 | 2 / 24 |
| serious Total, serious adverse events | 0 / 23 | 0 / 24 |
Outcome results
Primary
Number of Successful Pregnancies Defined as an Ongoing Pregnancy Over 20 Weeks Gestation, Per Number of Index Pregnancies
Time frame: 20 weeks gestation
Population: 47 women who achieved an index pregnancy, defined as the first pregnancy in the study, unless it resulted in a noneuploid miscarriage, ectopic, molar pregnancy or genetic termination, were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IVIG | Number of Successful Pregnancies Defined as an Ongoing Pregnancy Over 20 Weeks Gestation, Per Number of Index Pregnancies | 16 Successful pregnancies |
| Normal Saline | Number of Successful Pregnancies Defined as an Ongoing Pregnancy Over 20 Weeks Gestation, Per Number of Index Pregnancies | 15 Successful pregnancies |
p-value: <0.0595% CI: [0.41, 4.61]Chi-squared