Effect of Folic Acid Supplementation in Pregnancy on Preeclampsia-Folic Acid Clinical Trial (FACT)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,464
- 试验地点
- 72
- 主要终点
- Preeclampsia
研究概览
简要总结
To determine the efficacy of high dose folic acid supplementation for prevention of preeclampsia in women with at least one risk factor: pre-existing hypertension, pre-pregnancy diabetes (type 1 or 2), twin pregnancy, preeclampsia in a previous pregnancy, or body mass index ≥35. It was hypothesized that high dose (4.0 mg per day) supplementation starting in early pregnancy and continued throughout the entire pregnancy will lower the incidence of preeclampsia in pregnant women at high risk of developing preeclampsia.
详细描述
Preeclampsia is a complication of pregnancy which affects at least 5% of all pregnancies worldwide and has serious health consequences to these women and their babies. Preeclampsia is hypertension (high blood pressure) in pregnancy with proteinuria. Proteinuria is when protein is found in the urine, and it is a sign that the kidneys are not functioning properly. The only effective treatment for preeclampsia is delivery of the baby. Because delivery may be required before the anticipated date of delivery; preeclampsia is also one of the leading causes of preterm delivery and accounts for 25% of very low birth weight infants. Recent research has also shown that women who have had preeclampsia during pregnancy are more likely to be at risk for future cardiovascular events later in life.
Recently some studies have shown that supplementation with multivitamins containing folic acid is associated with a reduced risk of developing preeclampsia. These findings also suggested that for the prevention of preeclampsia, a high dose of folic acid (much higher than the amount of folate received from food intake or what is usually taken during pregnancy) may be needed.
A randomized controlled trial was conducted in 70 obstetrical centres in 5 countries (Argentina, Australia, Canada, Jamaica, and the UK) to evaluate the effect of high dose folic acid started in early pregnancy on the risk of developing preeclampsia in high-risk women. A sample size of 2464 allowed for 80% power and a 10% loss to follow-up/study withdrawal. Participants received either placebo or four 1.0 mg oral tablets of folic acid.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Capability of subject to comprehend and comply with study requirements
- •≥ 18 years of age at time of consent
- •Subject is taking ≤1.1 mg of folic acid daily at the time of randomization
- •Live fetus (documented positive fetal heart prior to randomization)
- •Gestational age between 8+0 and 16+6 weeks of pregnancy (Gestational age (GA) of subjects will be calculated based on the first day of the last menstrual period (LMP) or ultrasound performed before 12+
- •If early ultrasound and LMP dates differ by ≤ 7 days, base GA estimate on LMP date; if > 7 days, use early < 12+6 ultrasound)
- •Subject plans to give birth in a participating hospital site
- •Pregnant subjects must fulfill at least one of the following identified risk factors for pre-eclampsia (PE):
- •Pre-existing hypertension (documented evidence of diastolic blood pressure ≥ 90 mmHg on two separate occasions or at least 4 hours apart prior to randomization, or use of antihypertensive medication during this pregnancy specifically for the treatment of hypertension prior to randomization)
- •Pre-pregnancy diabetes (documented evidence of Type I or type II DM)
- •Twin pregnancy
- •Documented evidence of history of PE in a previous pregnancy
- •BMI > 35 kg/m2 within 3 months prior to this pregnancy and up to randomization of this pregnancy (documented evidence of height and weight to calculate BMI is required)
排除标准
- •Known history or presence of any clinically significant disease or condition which would be a contraindication to folic acid supplementation of up to 5 mg daily for the duration of pregnancy
- •Known major fetal anomaly or fetal demise
- •History of medical complications, including:
- •renal disease with altered renal function,
- •epilepsy,
- •cancer, or
- •use of folic acid antagonists such as valproic acid
- •Individual who is currently enrolled or has participated in another clinical trial or who received an investigational drug within 3 months of the date of randomization (unless approved by the Trial Coordinating Centre)
- •Known presence of:
- •Alcohol abuse (≥ 2 drinks per day) or alcohol dependence
- •Illicit drug/substance use and/or dependence
- •Known hypersensitivity to folic acid
- •Multiple Pregnancy (triplets or more)
- •Participation in this study in a previous pregnancy
研究组 & 干预措施
Folic Acid 4 mg
Folic Acid 1.0 mg x 4 tablets will be taken daily by oral administration. The majority of women in the study will routinely take 1.0 mg folic acid in a prenatal vitamin supplement, as recommended by their primary obstetrical provider; the study requirements do not require that participants change their practice. Therefore the actual total daily dose may be up to 5.1 mg of folic acid
干预措施: Folic Acid 4 mg (Drug)
Placebo
Women will be randomised in a 1:1 ratio to folic acid 4.0 mg or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Preeclampsia
时间窗: Participants will be followed from 20+0 weeks of gestational age until 42 days postpartum (after delivery)
PE is defined as diastolic blood pressure ≥90 mmHg on two occasions ≥4 hours apart and proteinuria developed in women greater than 20+0 weeks of gestation. Proteinuria is defined as: urinary protein ≥300mg in 24 hour urine collection OR in the absence of 24 hour collection, ≥2+ dipstick proteinuria, OR random protein-creatinine ratio ≥30mg protein/mmol. OR HELLP (Haemolysis, Elevated, Liver Enzymes, Low Platelets) syndrome defined as: Haemolysis (characteristic peripheral blood smear), Serum LDH ≥ 600U/L, Serum AST ≥ 70U/L, and Platelet count \<100 x109/L OR Superimposed pre-eclampsia, defined as history of pre-existing hypertension (diagnosed pre-pregnancy or before 20+0 weeks' gestation) with new proteinuria.
次要结局
- Preterm Birth(Participants will be followed from 20+0 weeks to 36+6 weeks of gestation)
- Perinatal Mortality(Participants will be followed from 20+0 weeks of gestation until 28 days of life.)
- Retinopathy of Prematurity(Infants born to the participant will be followed for the duration of hospital stay, or up to 6 weeks)
- Early Onset Sepsis(Infants born to the participants will be followed first 48 hours of life.)
- Premature Rupture of Membranes(Participants will be followed from randomization (8-16 weeks' completed gestation) until the onset of labor)
- Severe Preeclampsia(Participants will be followed from 20+0 weeks of gestation until delivery.)
- Maternal Death(Time Frame: Participants will be followed from 20+0 weeks of gestation until 42 days postpartum (after delivery))
- HELLP (Hemolysis, Elevated Liver Enzyme Levels & Low Platelet Count)(Participants will be followed from 20+0 weeks of gestation until delivery)
- Antenatal Inpatient Length of Stay(Participants will be followed from date of randomization (8-16 weeks' completed gestation) until admission for delivery)
- Stillbirth(Participants will be followed from 20+0 weeks of gestation up to delivery.)
- Spontaneous Abortion(Participants will be followed from randomization until 20+0 weeks of gestation)
- Placenta Abruption(Participants will be followed from 20+0 weeks of gestation until delivery)
- Necrotising Enterocolitis(Infants borm to the participants will be followed for the duration of hospital stay, or up to 6 weeks.)
- Intrauterine Growth Restriction (<3rd Percentile)(Participants will be followed from 20+0 weeks of gestation until delivery)
- Intrauterine Growth Restriction (<10th Percentile)(Participants will be followed from 20+0 weeks of gestation until delivery)
- Neonatal Death(Infants to the participants will be followed for 28 days after birth.)
- Intraventricular Hemorrhage (IVH)(Time Frame: Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks)
- Ventilation(Infants born to the participants will be followed for the duration of hospital stay, or up to 6 weeks.)
- Composite Severe Adverse Fetal/Neonatal Outcome(Outcomes included in the composite outcome were measured for each of their respective time frames, up to 6-weeks after birth)
- Need for Oxygen at 28 Days(Infants to the participants will be followed for 28 days after birth.)
- Length of Stay in 'High Level' Neonatal Care Unit(Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.)
- Periventricular Leukomalacia(Infants to the participants were followed for 28 days after birth.)
- Neonatal Intensive Care Unit (NICU) Admission(Infants to the participants will be followed for the duration of hospital stay, or up to 6 weeks.)