Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment: a randomised, double-blind, placebo-controlled trial

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2020-000256-35-DK

Enrollment

Registered

2020-09-14

Start date

2020-12-16

Completion date

Unknown

Last updated

2024-05-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Recurrent pregnancy loss after assisted reproductive technology treatment MedDRA version: 20.0 Level: LLT Classification code 10078356 Term: Recurrent pregnancy loss System Organ Class: 100000004868

Interventions

Trade Name: Privigen Product Name: Privigen Pharmaceutical Form: Infusion INN or Proposed INN: Human normal immunoglobulin Current Sponsor code: IVIg Other descriptive name: HUMAN NORMAL IMMUNOGLOBULI

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Women with = 2 consecutive pregnancy losses (miscarriages or biochemical pregnancies) = gestational week 10 after ART with the present partner Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 74 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: BMI =35 Age =41 years Significant uterine malformation(s) Known parental balanced chromosomal translocations =2 previous pregnancies with fetuses with known abnormal karyotype Patients with IgA deficiency, IgA-autoantibodies or hyperprolinaemia Anti-Müllerian hormone (AMH) <4 pmol/l if the planned IVF/ICSI cycle does not imply the use of donor egg. If IVF/ICSI with egg donation is planned, a low AMH value is not an exclusion criterion. Treatment with medication interacting with prednisolone: CYP3A4-inhibitors (fx erythromycin, itraconazol, ritonavir, lopinavir), CYP3A4-inductors (fx phenobarbital, phenytoin og rifampicin), loop diuretics, thiazides, amphotericin B, beta2-agonists, antidiabetics (metformin is acceptable), interleukin-2, somatropins, anticholinergics and regular treatment with NSAIDs. Patients with moderate/severe hypertension, diabetes mellitus, heart insufficiency, severe mental disorders, Cushing syndrome, myasthenia gravis, ocular herpes simplex, pheochromocytoma, systemic sclerosis, and moderate/severe renal dysfunction. Patients with a clinical or biochemical profile indicating need for heparin or levothyroxine treatment during pregnancy (see the description below) Previous treatment with IVIg Allergy to prednisolone and/or IVIg

Design outcomes

Primary

Measure	Time frame
Main Objective: In a randomized, double-blinded placebo-controlled trial we aim to investigate whether treatment with prednisolone and IVIg before and in early pregnancy improves the chance of a live birth in women undergoing treatment with artificial reproductive technologies (ART) after previous recurrent pregnancy losses after ART.;Secondary Objective: The study aims to investigate if treatment with IVIg combined with prednisolone is associated with adverse events to the women or her child, and whether the drugs can modulate leucocyte subsets in pheripheral blood. ;Primary end point(s): The primary endpoint is the percentage of participants with =1 normal, viable fetus at NT scan among all participants in each treatment group, and subsequently among participants with a positive pregnancy test after embryo transfer and among all participants except participants pregnant with a fetus having a confirmed chromosomal abnormality. Furthermore, the relative risk, absolute risk reduction, and adjusted risk ratio for this primary outcome will describe the primary outcome. The primary endpoint is also measured in subgroups based on diagnosis of primary and secondary RPL, respectively, i.e., no prior birth or a history of =1 previous birth after 22 weeks prior to RPL diagnosis. The primary analyses will be undertaken as 1.an Intention-to-Treat (ITT) analysis, including all patients who were allocated to either active or placebo treatment at the start of the ART cycle, even if they did not receive infusion with IVIg or albumin due to cancellation of embryo/blastocyst transfer. 2.a per-protocol (PP) analysis including patients who were randomized and received the allocated infusion of study medicine at embryo/blastocyst transfer and had this transfer performed. (excluded: : A verified complete or partial mola or ectopic pregnancy or an induced abortion after ET for social or genetic reason) ;Timepoint(s) of evaluation of this end point: The true measure for success in this	—

Measure

Time frame

Main Objective: In a randomized, double-blinded placebo-controlled trial we aim to investigate whether treatment with prednisolone and IVIg before and in early pregnancy improves the chance of a live birth in women undergoing treatment with artificial reproductive technologies (ART) after previous recurrent pregnancy losses after ART.;Secondary Objective: The study aims to investigate if treatment with IVIg combined with prednisolone is associated with adverse events to the women or her child, and whether the drugs can modulate leucocyte subsets in pheripheral blood. ;Primary end point(s): The primary endpoint is the percentage of participants with =1 normal, viable fetus at NT scan among all participants in each treatment group, and subsequently among participants with a positive pregnancy test after embryo transfer and among all participants except participants pregnant with a fetus having a confirmed chromosomal abnormality. Furthermore, the relative risk, absolute risk reduction, and adjusted risk ratio for this primary outcome will describe the primary outcome. The primary endpoint is also measured in subgroups based on diagnosis of primary and secondary RPL, respectively, i.e., no prior birth or a history of =1 previous birth after 22 weeks prior to RPL diagnosis. The primary analyses will be undertaken as 1.an Intention-to-Treat (ITT) analysis, including all patients who were allocated to either active or placebo treatment at the start of the ART cycle, even if they did not receive infusion with IVIg or albumin due to cancellation of embryo/blastocyst transfer. 2.a per-protocol (PP) analysis including patients who were randomized and received the allocated infusion of study medicine at embryo/blastocyst transfer and had this transfer performed. (excluded: : A verified complete or partial mola or ectopic pregnancy or an induced abortion after ET for social or genetic reason) ;Timepoint(s) of evaluation of this end point: The true measure for success in this

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Secondary

Measure	Time frame
Secondary end point(s): The secondary outcome is the frequency of maternal and fetal serious and non-serious adverse events/reactions, other reproductive outcomes (miscarriages with and without confirmed chromosomal abnormality, negative pregnancy tests, stillbirths, live births), perinatal outcomes (sex, birth weight, gestational age, admission to neonatal unit, congenital deformities, prematurity (<37 weeks of gestation), small for gestational age (SGA = birthweight <10th percentile), birth weight <2500 g), and pregnancy complications (preeclampsia, gestational hypertension, gestational diabetes, and instrumental delivery) in each two treatment groups. The secondary endpoint is the relative difference between groups in each of the secondary outcomes. Maternal adverse reactions and fetal adverse reactions that might be associated with the study medicine will be assessed continuously during treatment of the participants and until after birth for pregnant participants. And lastly, the effect of study medicine on immune cells and microvesicles in the participants' blood. ;Timepoint(s) of evaluation of this end point: The same as in the primary outcome; at the time when all patients, who become pregnant after their ART treatment, have ended their pregnancy.	—

Measure

Time frame

Secondary end point(s): The secondary outcome is the frequency of maternal and fetal serious and non-serious adverse events/reactions, other reproductive outcomes (miscarriages with and without confirmed chromosomal abnormality, negative pregnancy tests, stillbirths, live births), perinatal outcomes (sex, birth weight, gestational age, admission to neonatal unit, congenital deformities, prematurity (<37 weeks of gestation), small for gestational age (SGA = birthweight <10th percentile), birth weight <2500 g), and pregnancy complications (preeclampsia, gestational hypertension, gestational diabetes, and instrumental delivery) in each two treatment groups. The secondary endpoint is the relative difference between groups in each of the secondary outcomes. Maternal adverse reactions and fetal adverse reactions that might be associated with the study medicine will be assessed continuously during treatment of the participants and until after birth for pregnant participants. And lastly, the effect of study medicine on immune cells and microvesicles in the participants' blood. ;Timepoint(s) of evaluation of this end point: The same as in the primary outcome; at the time when all patients, who become pregnant after their ART treatment, have ended their pregnancy.

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Countries

Denmark

Contacts

Public ContactOle B. Christiansen

Ole B. Christiansen

olbc@rn.dk+4526821960

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026