E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Poly Cystic Ovarial Syndrome (PCOS) in pregnant women. PCOS should be diagnosed according to the Rotterdam Consensus criterias:
- at least 2 out of 3 criterias
1.PCO in at least one ovary
2.Oligo-/anovulation (clinically diagnosed as oligo-/amenorrhea,i.e. menstrual cycles > 35 days or <10 menstruations/year
3.Hyperandrogenism; clinical or biochemical
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065161 |
E.1.2 | Term | Polycystic ovarian syndrome |
E.1.2 | System Organ Class | 100000004872 |
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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 overall aim and primary endpoint of the PregMet 2 Study is to investigate whether metformin prevents late miscarriages and preterm deliveries in PCOS women treated with metformin from first trimester of pregnancy to delivery in a large, randomized, controlled, multi-centre trial setting. |
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E.2.2 | Secondary objectives of the trial |
Secondary endpoints
• NICU admissions and total number of days in NICU/baby
• No. of patients hospitalized (except delivery and post partum)
• Total number of hospitalization days/ hospitalized participant
• The prevalence of gestational diabetes
• The prevalence of preeclampsia
Tertiary endpoints
• Weight gain in pregnancy
• Newborn data
• Birth weight
• Birth length
• Head Circumference
• Apgar score/ pH , BE from umbilical cord blood
• Malformations
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion criteria
• Age: 18-45 years
• PCOS diagnosed or reconfirmed according to Rotterdam 2003 criteria, not more than 5 years prior to inclusion.
• Mode of conception: Any
• Single, viable fetus, diagnosed by vaginal ultrasound
• Gestational week at inclusion: week 6 + 0 to 12 + 0.
• Wash out for metformin: at least 7 days
• Able to communicate fluently in the official language at the study cite or English
• Informed consent |
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E.4 | Principal exclusion criteria |
Exclusion criteria
• Any type of diabetes (except GDM in former pregnancy).
• Known liver disease or ALAT > 100 IU/L
• Known kidney disease or creatinine > 110 μmol/L
• Known alcohol or drug abuse
• Use of drugs interfering with metformin: erytromycin (or other macrolides), cimetidin, anticoagulation therapy
• Unsuitable for participation of other reasons
• Participating in other medical trials in the same period of time
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoints
• The combined incidence of late miscarriages and preterm births. This includes spontaneous births, induced vaginal deliveries and operative deliveries on medical indications.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated when the last participant of the studygroup has delivered |
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E.5.2 | Secondary end point(s) |
Secondary endpoints
• NICU admissions and total number of days in NICU/baby
• No. of patients hospitalized (except delivery and post partum)
• Total number of hospitalization days/ hospitalized participant
• The prevalence of gestational diabetes
• The prevalence of preeclampsia
Tertiary endpoints
• Weight gain in pregnancy
• Newborn data
• Birth weight
• Birth length
• head circumference
• Apgar score/ pH , BE from umbilical cord blood
• Malformations
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated when the last participant of the studygroup given birth |
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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 | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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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For the participating individuals the trial ends at delivery (or spontaneous pregnancy loss). We plan to follow up both women and offspring after delivery. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |