Preeclampsia
Conditions
Keywords
Preterm preeclampsia, Aspirin, Metformin
Brief summary
This is a prospective, multicenter, randomized controlled, double-blind trial of three treatment arms: (1) aspirin 75 mg/day vs. (2) aspirin 150 mg/day vs. (3) aspirin 75 mg/day with metformin 1.5 g/day from the first trimester to compare the incidence of preterm preeclampsia with delivery at \<37 week's gestation between the treatment arms, in order to determine the optimal therapeutic intervention for the prevention of preterm preeclampsia among Chinese women at high-risk of preeclampsia.
Detailed description
All women with singleton pregnancies who are attending for their routine hospital visit at 11-13 weeks' gestation will be invited to undergo screening for preeclampsia. We use a Bayes theorem-based method that combines maternal characteristics, medical and obstetric history together with mean arterial pressure (MAP) and serum placental growth factor (PlGF) level. Women who are deemed high-risk following first trimester combined screening (cutoff corresponding to a screen positive rate of 10%, e.g ≥1 in 80) will be invited to participate in the 3-arm randomized controlled trial.
Interventions
DRUG75 mg acetylsalicylic acid
75 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral
DRUG1.5g Metformin
up to 1.5 g metformin (C4H11N5, CAS number 657-24-9) daily, Oral Dose increases from 0.5g to 1.0g to 1.5g
DRUG150 mg acetylsalicylic acid
150 mg acetylsalicylic acid (C9H8O4, CAS number 50-78-2) daily, Oral
DRUGPlacebo of acetylsalicylic acid and Metformin
Pills with shape, color and smell same with acetylsalicylic acid and metformin, daily, oral
Sponsors
Obstetrics & Gynecology Hospital of Fudan University
Shanghai First Maternity and Infant Hospital
West China Second University Hospital
Peking University First Hospital
Chinese University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
PI, participating research doctors, pharmacists at the local clinical trial pharmacy, project managers and others involved in the trial are all blinded to the investigational medicinal product (IMP). The tablets and capsules will be identical, so it will not be possible to distinguish between the different IMPs.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Singleton pregnancies * Live fetus at 11-13 weeks' gestation * High-risk for preterm preeclampsia at 11-13 weeks by the algorithm combining maternal characteristics, medical and obstetric history, MAP and serum PlGF * Informed and written consent
Exclusion criteria
* Age \<18 years old * Multiple pregnancies * Treatment with low-dose aspirin and metformin at the time of screening * Pregnancies complicated by major fetal abnormality identified during the first trimester * Women with learning difficulties, or serious mental illness * Bleeding disorders such as Von Willebrand's disease * Active peptic ulceration or gastrointestinal bleeding * Hypersensitivity to aspirin, metformin hydrochloride and other biguanides * Treatment with long term nonsteroidal anti-inflammatory medication * Hyperemesis gravidarum * Renal, liver or heart failure * A serious medical condition * Concurrent participation in another drug trial or at any time within the previous 28 days * Any other reason the clinical investigators think will prevent the potential participant from complying with the trial protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of preterm preeclampsia(<37 weeks) | ≥20 weeks to <37 weeks of gestation | Preeclampsia will be defined as per the International Society for the Study of Hypertension in Pregnancy.The Proportions of delivery with preterm-preeclampsia between different intervention groups will be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse outcome of pregnancy at <34 weeks. | <34 weeks of gestation | including preeclampsia requiring delivery, gestational age (SGA; \<5th percentile) requiring delivery, miscarriage or still birth or placental abruption. |
| Adverse outcome of pregnancy at ≥37 weeks | ≥37 weeks of gestation | including preeclampsia requiring delivery, gestational age (SGA; \<5th percentile) requiring delivery, stillbirth or placental abruption. |
| Neonatal mortality | During the first 28 days of life (0-27days) | A neonatal death is a death during 0-27 days of life. |
| Neonatal morbidity | During the first 28 days of life (0-27days) | Composite neonatal morbidity (any one of the following): \>grade II intra-ventricular hemorrhage; neonatal sepsis confirmed by cultures; neonatal anemia requiring transfusion; respiratory distress syndrome requiring surfactant and ventilation; necrotising enterocolitis requiring surgical intervention. |
| Adverse outcome of pregnancy at <37 weeks. | <37 weeks of gestation | including preeclampsia requiring delivery, gestational age (SGA; \<5th percentile) requiring delivery, miscarriage or still birth or placental abruption. |
| Stillbirth or neonatal death | At delivery | Stillbirth: the death of a baby before or during birth after 24 weeks of gestation. Neonatal death: the death of a baby within the first 28 days of life. |
| <34 weeks and <37 weeks spontaneous preterm delivery | At spontaneous delivery | Spontaneous delivery at \<34 weeks(early preterm) and at \<37 weeks(total preterm) includes those with spontaneous onset of labor and those with preterm pre-labor rupture of membranes (PPROM). |
| Gestational age | At delivery | Gestation is the period of time between conception and birth. During this time, the baby grows and develops inside the mother's womb. Gestational age is the common term used during pregnancy to describe how far along the pregnancy is. It is measured in weeks, from the first day of the woman's last menstrual cycle to the current date. A normal pregnancy can range from 38 to 42 weeks. |
| Neonatal birthweight below the 3rd,5th and 10th centile. | At delivery | Birthweight and birthweight percentile for gestational age at delivery is calculated using a normal range derived in a Chinese population. |
Countries
China
Contacts
Primary ContactChiu Yee, Liona Poon, MD
Backup ContactChi Chiu Wang, PhD
Outcome results
None listed