E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent pregnancy losses. Women with >3 subsequent pregnancy losses or 3 pregnancy losses of which one was a 2. trimester loss. |
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E.1.1.1 | Medical condition in easily understood language |
Recurrrent pregnancy losses |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072314 |
E.1.2 | Term | Pregnancy loss |
E.1.2 | System Organ Class | 100000004868 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The objective of the trial is to investigate whether Plaquenil (Hydroxychloroquin sulfate) prior to and during pregnancy increases the chance of live birth in women with unexplained recurrent pregnancy losses compared with placebo.
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E.2.2 | Secondary objectives of the trial |
Weight at birth, duration of pregnancy, Apgar-score 5 minutes after delivery and the amount of days at neonatal department in the Plaquenil versus the placebo group.
The immunological status (cytokine profile) in the women who obtains a live birth compared with the women with another pregnancy loss as well as in the women in the Plaquenil group compared with the placebo group. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
>3 recurrent subsequent spontaneous pregnancy losses or 3 recurrent subsequent spontaneous pregnancy losses of which one is a second trimester loss. |
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E.4 | Principal exclusion criteria |
1) Age below 18 or above 40 at the time of achieved pregnancy
2) Significant uterine abnormalities diagnosed by hysterosalpingography/hysteroscopy/hydrosonography.
3) Significant chromosome abnormalia (especially tranlocations) in the couple
4) Menstruation cycle < 23 days or > 35 days
5) Lupusanticoagulans or IgG anticardiolipinantibody concentration ≥40 GPL kU/l or plasma homocystein ≥25 mikrogr./l after recurrent measurements with 8 weeks intervals before pregnancy
6) Positive test for HIV or tests suggestive på hepatitis B or C carrier state.
7) Psoriasis, retinopathy and adverse hearing loss (contra indications for Plaquenil)
8) Chronical diseases requiring anti inflammatory medicine or medicine potentially harmfull to pregnancy: corticosteroids, acetylsalicyle acid, indometacin, simvastatin, imurel ect.. Periodic paracetamol use is allowed.
9) >1 previous live birth
10) Previous participation in the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
Chance of live birth in women with unexplained recurrent pregnancy losses in women treated with Plaquenil compared with placebo.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
When trial is completed - 186 patients included and they all have either a live birth or another pregnancy loss. |
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E.5.2 | Secondary end point(s) |
Weight at birth, duration of pregnancy, Apgar-score 5 minutes after delivery and the amount of days at neonatal department in the Plaquenil versus the placebo group.
The immunological status (cytokine profile) in the women who obtains a live birth compared with the women with another pregnancy loss as well as in the women in the Plaquenil group compared with the placebo group. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
When trial is completed - 186 patients included and they all have either a live birth or another pregnancy loss. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The trial ends when the last women of the trial (n=186) has either had a live birth or a spontaneous pregnancy loss. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |