E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10004953 |
E.1.2 | Term | Birth premature |
E.1.2 | System Organ Class | 10036585 - Pregnancy, puerperium and perinatal conditions |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10007607 |
E.1.2 | Term | Cardiac septal defects congenital |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041524 |
E.1.2 | Term | Spina bifida |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 |
1. What is the effect of a high (4.0 mg) versus low (0.4 mg) dose of folic acid supplementation from 4 weeks before conception to 12 weeks of gestation on the prevalence of folic acid related congenital anomalies?
2. What is the effect of 0.8 mg folic acid supplementation versus 0,2 folic acid supplementation from 12 weeks of gestation to the end of pregnancy on the prevalence of preterm birth and preeclampsia?
|
|
E.2.2 | Secondary objectives of the trial |
3. Which side effects of periconceptional and prenatal folic acid use are reported by trail participants?
4. What associations between study groups and the incidence, severity and types of side effects reported, can be identified?
a. During the first period (until 12 weeks of gestation);
b. During the second period (from 12 weeks of gestation until the end of the pregnancy).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All women living in the Northern region of the Netherlands of 18 to 45 years old who want to become pregnant within 12 months are eligible for participation in the study. |
|
E.4 | Principal exclusion criteria |
When the participant appears to have a multiple pregnancy, she will be excluded for further participation, because these women are advised by midwifes to use 1 mg FA. Women who had previous offspring with NTD and other women who take high doses of FA for any other reason and women who use FA-antagonists will be excluded from the study.
Further exclusion criteria are:
a) no informed consent given
b) not understanding Dutch
c) already pregnant at time of inclusion or within 4 weeks after start intervention
d) planning to move to an area where the study is not implemented
e) recently or at present using folic acid antagonists or antifolates or other drugs influencing the folic acid metabolism (methotrexaat, pyrimethamine, trimethoprim)
f) being affected by epilepsy, diabetes, megaloblastic anaemia and/or cancer (previous cancer or abnormal PAP smears)
g) being allergic to folic acid or any other ingredient of the pills used in this study
h) take defined dosages of folic acid for directions other than those listed in the above exclusion criteria.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
FA related congenital anomalies and preterm birth. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at birth and during first year postpartum |
|
E.5.2 | Secondary end point(s) |
- Birth weight, obtained from medical records
- preeclampsia (defined as a systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg after 20 weeks of gestation among women with previously normal blood pressure, combined with proteinuria (≥ 300 mg/24 hours)), obtained from medical records
- compliance with intervention: Women will be asked to return all pills they have not used within a 12 week period to the pharmacy, in order to check compliance with folic acid supplementation. Additionally, each time they pick up their supplements at the pharmacy, they will be asked to fill in a short questionnaire including questions on compliance with the intervention (MARS-5 questionnaire). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Compliance: when picking up new folic acid supplements at pharmacy (every 3 months)
others: at birth. |
|
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 | No |
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) | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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
|
One year after last participant gave birth.
Birth defects are registered during the first year after birth. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |