E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
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 |
PRINCIPAL OBJECTIVE: To test the hypothesis that in women with unexplained recurrent miscarriages, progesterone (2 x 200mg pessaries, twice daily), started as soon as possible after a positive pregnancy test (and no later than 6 weeks gestation) and continued to 12 weeks of gestation, compared to placebo, increases live births beyond 24 completed weeks of pregnancy by at least 10%. |
|
E.2.2 | Secondary objectives of the trial |
SECONDARY OBJECTIVES: 1. To test the hypothesis that progesterone improves various pregnancy and neonatal outcomes (such as reduction in miscarriage rates and improvement in survival at 28 days of neonatal life). 2. To test the hypothesis that progesterone, compared to placebo, does not incur substantial adverse effects to the mother or the neonate (such as genital anomalies in the neonate). 3. To explore differential or subgroup effects of progesterone in various prognostic subgroups. (Three subgroup analyses are planned: a)by maternal age (<35, ≥35), b) Number of previous miscarriages (3, ≥4) and c) presence or absence of polycystic ovaries). 4. To perform an economic evaluation for cost-effectiveness. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Women with unexplained recurrent miscarriages (3 or more first trimester miscarriages). 2. Age 18 - 39 years at randomisation (likelihood of miscarriages due to chromosomal aberrations is higher in older women; such miscarriages are unlikely to be prevented by progesterone therapy). 3. Spontaneous conception (as confirmed by urinary pregnancy tests). 4. Willing and able to give informed consent. |
|
E.4 | Principal exclusion criteria |
1. Inability to conceive spontaneously within 1 year of recruitment. 2. Antiphospholipid syndrome (lupus anticoagulant and/ or anticardiolipin antibodies [IgG or IgM]); other recognised thrombophilic conditions (testing according to usual clinic practice). 3. Intrauterine abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram or hysteroscopy). 4. Fibroids distorting the uterine cavity. 5. Abnormal parental karyotype. 6. Other identifiable causes of recurrent miscarriages (tests initiated only if clinically indicated): e.g. diabetes, thyroid disease and SLE. 7. Current heparin therapy. 8. Contraindications to progesterone use (e.g. allergy to progesterone). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary outcome: live birth beyond 24 completed weeks of gestation (We decided on this as the clinically most relevant outcome following discussions amongst health care professionals, patients, and patient representative bodies) |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
It is the last encounter (whether visit or telephonic interview) with the last participant undergoing the trial. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |