PI4 — Исследование, оценивающее возможность продления беременности метформином при преждевременной преэклампсии (PI4)
Вмешательство 4 при преэклампсии — тройное слепое рандомизированное контролируемое исследование III фазы по оценке возможности применения метформина для продления беременности при преждевременной преэклампсии
Preterm preeclampsia is a severe condition for both the mother and the fetus. Currently, the only treatment available to stop disease progression is termination/delivery of the fetus and placenta. Therefore, preterm preeclampsia carries the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth. There is evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition. This multi centre double blind randomised controlled trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Nordic setting.
Обзор исследования
Статус
Условия
Вмешательство/лечение
Подробное описание
Preeclampsia is globally responsible for 60,000 maternal deaths per year, and far greater numbers of fetal losses. Preterm preeclampsia is a severe variant with the highest rates of neonatal morbidity and mortality due to iatrogenic preterm birth (clinicians are forced to deliver the baby preterm for maternal or fetal health reasons).
There is preclinical evidence suggesting metformin, a drug commonly used to treat diabetes in and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising the possibility that it could be used to treat the condition.
Previous research from the Preeclampsia Intervention 2 trial (PI2) show that metformin was able to delay delivery in early preterm preeclampsia. Metformin extended release (ER) was associated with a median 7.6-day prolongation of pregnancy (geometric mean ratio (GMR) 1.39 (95% CI 0.99 to 1.96) P=0.057).Trends towards increased birthweight (mean difference 110gm (95%CI -80 to 300), a decreased length of stay at the neonatal intensive care unit (median difference 5.0 days less; GMR 0.86, 95% CI 0.62 to 1.2) and a shorter period of admission in any neonatal ward (median difference 12.0 days less; GMR 0.82, 95% CI 0.57 to 1.18) in the metformin ER group were found. Importantly, while gastrointestinal side effects were common, no serious adverse events related to trial medications were observed.
The PI 2 trial has shown that metformin may be a disease modifying treatment for preterm preeclampsia. The trial is being repeated in a larger scale in the PI3 trial in South Africa to also assess neonatal outcomes. In the Nordic countries, the demographics of the population are different and expectant management of preeclampsia allows for the women to reach 37 weeks of gestation as opposed to 34 weeks of gestation in the PI2 trial. This trial aims to investigate if metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a Nordic setting. Follow up of mothers and children will be carried out two years post partum.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 3
Контакты и местонахождение
Контакты исследования
- Имя: Pia Gudmundsson, PhD
- Номер телефона: 0046-313434327
- Электронная почта: pia.gudmundsson@obgyn.gu.se
Учебное резервное копирование контактов
- Имя: Lina Bergman, Associate Professor
- Номер телефона: 0046-3134307
- Электронная почта: lina.bergman@obgyn.gu.se
Места учебы
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Lørenskog, Норвегия, N-1474
- Рекрутинг
- Akershus University Hospital
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Контакт:
- Camilla Haavaldsen, PhD
- Номер телефона: 0047-95763946
- Электронная почта: Marit.Camilla.Haavaldsen@ahus.no
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Главный следователь:
- Camilla Haavaldsen, PhD
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Oslo, Норвегия, 0372
- Рекрутинг
- Oslo University Hospital
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Контакт:
- Trond Michelsen, Professor
- Номер телефона: 0047-23072619
- Электронная почта: trmi1@ous-hf.no
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Главный следователь:
- Ingvil Krarup Sørbye, Professor
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Helsinki, Финляндия, 00290
- Рекрутинг
- Helsinki University Hospital
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Контакт:
- Pia Villa, Associate Professor
- Номер телефона: 00358-405389779
- Электронная почта: pia.villa@helsinki.fi
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Главный следователь:
- Pia Villa, Associate Professor
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Tampere, Финляндия, 33520
- Рекрутинг
- Tampere University Hospital
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Контакт:
- Hannele Laivuori, Professor
- Номер телефона: 00358-504154871
- Электронная почта: hannele.laivuori@tuni.fi
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Главный следователь:
- Hannele Laivuori, Professor
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Borås, Швеция, 50455
- Рекрутинг
- Södra Älvsborgs Hospital
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Контакт:
- Stina Berver
- Номер телефона: 0046-336163281
- Электронная почта: stina.berver@vgregion.se
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Главный следователь:
- Lina Bergman, Associate Professor
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Falun, Швеция, 79129
- Рекрутинг
- Falu Lasarett
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Контакт:
- Susanne Hesselman, PhD
- Номер телефона: 0046-23492351
- Электронная почта: susanne.hesselman@regiondalarna.se
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Gothenburg, Швеция, 416 85
- Рекрутинг
- Sahlgrenska University Hospital
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Контакт:
- Pia Gudmundsson, PhD
- Электронная почта: pia.gudmundsson@obgyn.gu.se
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Контакт:
- Lina Bergman, Associate professor
- Номер телефона: 0046-3134307
- Электронная почта: lina.bergman@obgyn.gu.se
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Linköping, Швеция, 581 85
- Рекрутинг
- Linköping University Hospital
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Контакт:
- Caroline Lilliecreutz, Associate professor
- Номер телефона: 0046-101034909
- Электронная почта: caroline.lilliecreutz@liu.se
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Контакт:
- Marie Blomberg, Professor
- Электронная почта: marie.blomberg@regionostergotland.se
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Lund, Швеция, 221 85
- Рекрутинг
- Skåne University Hospital
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Контакт:
- Emma von Wowern, PhD
- Номер телефона: 004640336809
- Электронная почта: emma.von_wowern@med.lu.se
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Контакт:
- Simon Timpka, Associate professor
- Номер телефона: 0046-46171000
- Электронная почта: simon.timpka@med.lu.se
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Malmö, Швеция, 205 02
- Рекрутинг
- Skåne University Hospital
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Контакт:
- Simon Timpka, Ass Prof
- Номер телефона: 0046-46171000
- Электронная почта: simon.timpka@med.lu.se
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Skövde, Швеция, 549 49
- Рекрутинг
- Skaraborg Hospital
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Контакт:
- Emelie Ottosson, Senior consultant
- Номер телефона: +46-73729 98 70
- Электронная почта: emelie.ottosson@vgregion.se
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Stockholm, Швеция, 17176
- Рекрутинг
- Karolinska University Hospital Solna
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Контакт:
- Anna Sandström, Associate Professor
- Номер телефона: 0046-739829820
- Электронная почта: anna.sandstrom@ki.se
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Контакт:
- Ängla Mantel, Associate Professor
- Электронная почта: angla.mantel@ki.se
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Stockholm, Швеция, 182 88
- Рекрутинг
- Danderyd Hospital
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Контакт:
- Sophia Hugo Aronzon, PhD student
- Номер телефона: 0046-72-582 21 57
- Электронная почта: hugo.aronzon@regionstockholm.se
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Stockholm, Швеция, 14157
- Рекрутинг
- Karolinska University Hospital Huddinge
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Контакт:
- Anna Sandström, Associate Professor
- Номер телефона: 0046-739829820
- Электронная почта: anna.sandstrom@ki.se
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Контакт:
- Ängla Mantel, Associate Professor
- Электронная почта: angla.mantel@ki.se
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Trollhättan, Швеция, 461 74
- Рекрутинг
- Norra Älvsborgs County Hospital
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Главный следователь:
- Lina Bergman, Associate Professor
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Контакт:
- Carina Bejlum
- Номер телефона: 0046-104350000
- Электронная почта: carina.bejlum@vgregion.se
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Umeå, Швеция, 901 85
- Рекрутинг
- Norrland´s University Hospital
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Контакт:
- Marie-Therese Vinnars, PhD
- Номер телефона: 0046-739426777
- Электронная почта: marie-therese.vinnars@umu.se
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Главный следователь:
- Marie-Therese Vinnars, PhD
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Uppsala, Швеция, 75237
- Рекрутинг
- Uppsala University Hospital
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Контакт:
- Linda Lindström, PhD
- Номер телефона: 0046-186115729
- Электронная почта: linda.lindstrom@uu.se
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Västerås, Швеция, 72335
- Рекрутинг
- Västmanlands Hospital Västerås
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Контакт:
- Merit Kullinger
- Номер телефона: 0046-21173155
- Электронная почта: merit.kullinger@regionvastmanland.se
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Главный следователь:
- Linda Lindström, PhD
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- A diagnosis of preeclampsia (defined as hypertension in combination with significant proteinuria (albumin/creatinine ratio >8 mg/mmol, protein/creatinine ratio>30 mg/mmol or >2+ protein on a urinary dipstick) has been made by the attending clinician
- The managing clinicians have made the assessment to proceed with expectant management.
- The subject has given written consent to participate in the study.
- The woman must be 18 years of age or older
- The gestational age is between 22+0 weeks to 33+6 weeks with a viable fetus
- The woman carries a singleton pregnancy
Exclusion Criteria:
- Contraindications to treatment with metformin as outlined in SmPC
- Contraindications for expectant management of preeclampsia such as an immediate indication for delivery according to SFOG guidelines for preeclampsia (https://www.sfog.se/media/338533/pe-riktlinje-230214.pdf).
- Type 1 Diabetes Mellitus
- Current use of metformin
- Known or suspected allergies against metformin
- Reluctance or language difficulties that result in difficulty understanding the meaning of study participation
- Unable to understand the informed consent process
- Previous participation in the study
- Established fetal compromise that necessitates imminent delivery (including planned delivery after 48 hours of corticosteroid treatment). This will be decided by the clinical team before expectant management is offered to the patient.
- Suspicion of a major known fetal anomaly or malformation.
- Renal disease or dysfunction, suggested by a creatinine level greater than or equal to 125 µmol/L or rapidly declining renal function
- Known acute or chronic metabolic acidosis, including diabetic ketoacidosis
- Not suitable for inclusion by the opinion of the investigator
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Рандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Тройной
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Активный компаратор: Metformin ER
Metformin ER oral tablet 500 mg three times daily and increased to one gram (two tablets) three times daily as tolerated. |
Metformin ER, one gram three times daily taken orally. Once the participants have been recruited, they will start by taking one 500 mg tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia.
Другие имена:
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Плацебо Компаратор: Placebo
1 placebo tablet three times daily and increased to 2 placebo tablets three times daily as tolerated. |
Placebo, two tablets three times daily taken orally. Once the participants have been recruited, they will start by taking one tablet three times a day. If well tolerated it will be increased day two to a maximum of two tablets three times a day. Treatment will continue until delivery. If there are side effects that are not tolerable, the dose will be decreased and the participant will remain blinded. Each participant will keep a treatment diary and number of tablets taken will be documented by the participant or hospital staff. The study will not alter or interfere with treatment or care routinely given for preterm preeclampsia. |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Pregnancy prolongation
Временное ограничение: From randomisation to delivery, measured in days and hours, up to 105 days
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Length of pregnancy from diagnosis of preeclampsia to delivery |
From randomisation to delivery, measured in days and hours, up to 105 days
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Time for neonatal care
Временное ограничение: From birth to discharge from neonatal care, measured in days and hours, up to 126 days
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Time for neonatal care from birth to discharge |
From birth to discharge from neonatal care, measured in days and hours, up to 126 days
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Neonatal birth weight
Временное ограничение: At birth
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Birth wight measured in grams |
At birth
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Другие показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Occurrence of maternal death
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of maternal death |
Registered from inclusion to two month post partum
|
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Occurrence of Eclampsia
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of Eclampsia |
Registered from inclusion to two month post partum
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Occurrence of Cerebral vascular event
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of Cerebral vascular event |
Registered from inclusion to two month post partum
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Occurrence of posterior reversible encephalopathy syndrome
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of posterior reversible encephalopathy syndrome |
Registered from inclusion to two month post partum
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Occurrence of pulmonary edema
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of pulmonary edema |
Registered from inclusion to two month post partum
|
|
Occurrence of left ventricular failure
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of left ventricular failure |
Registered from inclusion to two month post partum
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Occurrence of renal dialysis
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of renal dialysis |
Registered from inclusion to two month post partum
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Occurrence of renal failure
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of renal failure:≥ 90 µmol/L or no urinary output for 6 hours |
Registered from inclusion to two month post partum
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Occurrence of elevated liver transaminases
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of elevated liver transaminases: ALT or AST ≥ 2 times highest normal value (ALAT >1.5 µkat/L and ASAT > 1.2 µkat/L) |
Registered from inclusion to two month post partum
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Occurrence of HELLP syndrome
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of HELLP (Haemolysis, elevated liver enzymes and low platelets) syndrome |
Registered from inclusion to two month post partum
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Occurrence of thrombocytopenia
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of thrombocytopenia (platelets <100 X 109/L) |
Registered from inclusion to two month post partum
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Occurrence of liver haematoma or rupture
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of liver haematoma or rupture |
Registered from inclusion to two month post partum
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Occurrence of admission to an intensive care unit
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of admission to an intensive care unit |
Registered from inclusion to two month post partum
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Occurrence of severe hypertension
Временное ограничение: Registered from inclusion to two month post partum
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Occurrence of severe hypertension (BP>160/110 mm Hg) |
Registered from inclusion to two month post partum
|
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Occurrence of disseminated intravascular coagulation
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of disseminated intravascular coagulation |
Registered from inclusion to two month post partum
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Occurrence of caesarean section
Временное ограничение: At birth
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Occurrence of caesarean section |
At birth
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Occurrence of major postpartum hemorrhage
Временное ограничение: At birth
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Occurrence of major postpartum hemorrhage (>1000 ml) |
At birth
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Occurrence of thromboembolic disease
Временное ограничение: Registered from inclusion to two month post partum
|
Occurrence of thromboembolic disease: deep venous thrombosis or pulmonary embolism |
Registered from inclusion to two month post partum
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Duration of maternal postpartum hospital stay
Временное ограничение: Registered from birth to hospital discharge
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Duration of maternal postpartum hospital stay (days) |
Registered from birth to hospital discharge
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Number of antihypertensive drugs
Временное ограничение: At discharge
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Number of antihypertensive drugs at discharge after delivery |
At discharge
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Duration of antihypertensive medication
Временное ограничение: From inclusion to two month postpartum
|
Duration of antihypertensive medication (days) |
From inclusion to two month postpartum
|
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Occurrence of intrauterine fetal demise
Временное ограничение: From inclusion to birth
|
Occurrence of intrauterine fetal demise |
From inclusion to birth
|
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Occurrence of neonatal death
Временное ограничение: From inclusion to two month post partum
|
Occurrence of neonatal death |
From inclusion to two month post partum
|
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Occurrence of growth restriction at birth
Временное ограничение: At birth
|
Occurrence of growth restriction at birth (less than 2 standard deviations from median weight from Swedish birth weight growth curves). |
At birth
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Occurrence of grade 3 or 4 intraventricular hemorrhage
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of grade 3 or 4 intraventricular hemorrhage |
Registered from birth to two month post partum
|
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Occurrence of necrotizing enterocolitis
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of necrotizing enterocolitis |
Registered from birth to two month post partum
|
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Occurrence of reversed a-wave in the ductus venosus
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of reversed a-wave in the ductus venosus |
Registered from birth to two month post partum
|
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Occurrence of persistent reversed flow in the umbilical artery
Временное ограничение: Registered from inclusion to birth
|
Occurrence of persistent reversed flow in the umbilical artery |
Registered from inclusion to birth
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Occurrence of redistribution in the middle cerebral artery
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of redistribution in the middle cerebral artery |
Registered from birth to two month post partum
|
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Occurrence of low APGAR score
Временное ограничение: At birth
|
Occurrence of low APGAR score, defined as less than 4 at 5 minutes |
At birth
|
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Occurrence of umbilical artery pH below 7.1
Временное ограничение: At birth
|
Occurrence of umbilical artery pH below 7.1 |
At birth
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Occurrence of invasive ventilation, intubation and mechanical ventilation or non-invasive ventilatione outcome
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of invasive ventilation, intubation and mechanical ventilation or non-invasive ventilation; continuous positive airway pressure (CPAP) support or high flow nasal oxygen |
Registered from birth to two month post partum
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Occurrence of grade III/IV hyaline membrane disease
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of grade III/IV hyaline membrane disease |
Registered from birth to two month post partum
|
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Occurrence of surfactant use
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of surfactant use |
Registered from birth to two month post partum
|
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Occurrence of retinopathy of prematurity
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of retinopathy of prematurity |
Registered from birth to two month post partum
|
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Occurrence of neonatal sepsis
Временное ограничение: Registered from birth to two month post partum
|
Occurrence of neonatal sepsis |
Registered from birth to two month post partum
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Tolerability and safety
Временное ограничение: From inclusion to birth
|
Severity of nausea measured by PHASE-20 Severity of vomiting measured by PHASE-20 Severity of diarrhoea measured by PHASE-20 Severity of headache measured by PHASE-20 |
From inclusion to birth
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Tolerability and safety
Временное ограничение: From inclusion to birth
|
Occurrence of lactic acidosis (blood pH< 7.35 or blood lactate> 5 mM) |
From inclusion to birth
|
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Tolerability and safety
Временное ограничение: From inclusion to birth
|
Drug adherence (measured by treatment diary) |
From inclusion to birth
|
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Pre-eclampsia-related biomarkers
Временное ограничение: From inclusion to two years post partum
|
Concentrations of Soluble Fms-like tyrosine kinase-1 Concentrations of Placental growth factor Concentrations of Soluble endoglin |
From inclusion to two years post partum
|
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Gut and vaginal microbiome composition
Временное ограничение: From inclusion to two years post partum
|
Omics-based analysis of the microbiome |
From inclusion to two years post partum
|
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Breastfeeding initiation
Временное ограничение: From birth to two month postpartum
|
Breastfeeding initiation (measured by unvalidated breastfeeding questionnaire with no score) |
From birth to two month postpartum
|
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Depressive symptoms
Временное ограничение: From inclusion to two years post partum
|
Depressive symptoms (measured by the Edinburgh Postnatal Depression Scale; 0-30, with higher scores indicating higher self-esteem) |
From inclusion to two years post partum
|
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Self-esteem
Временное ограничение: From inclusion to two years post partum
|
Self-esteem (measured by The Rosenberg Self-Esteem Scale; 0-30, higher scores indicating higher self-esteem) |
From inclusion to two years post partum
|
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Perceived stress
Временное ограничение: From inclusion to two years postpartum
|
Perceived stress (measured by the 10-item Perceived Stress Scale; 0-40, with higher scores indicating greater perceived stress) |
From inclusion to two years postpartum
|
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Breastfeeding self-efficacy
Временное ограничение: From birth to two month postpartum
|
Breastfeeding self-efficacy (measured by the Breastfeeding Self-Efficacy Scale-Short Form; 14-70, higher score= greater breastfeeding self-efficacy) |
From birth to two month postpartum
|
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Health-related quality of life
Временное ограничение: From inclusion to two years post partum
|
Health-related quality of life (measured using the EQ-5D-5L (the official name) and reported as the EQ-5D-5L index value and the EQ VAS [0-100]). EQ-5D-5L index values will be derived using country-specific value sets where available; higher index values indicate better health-related quality of life. The EQ VAS ranges from 0 to 100, with higher scores indicating better self-rated health) |
From inclusion to two years post partum
|
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Parental-infant bonding
Временное ограничение: From birth to two month post partum
|
Parental-infant bonding (measured by the Postpartum Bonding Questionnaire; 0-125, higher score= greater impairment/difficulties in parent-infant bonding) |
From birth to two month post partum
|
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Health economic outcomes
Временное ограничение: From birth to two years post partum
|
Cost-effectiveness short-term: direct healthcare costs (based on drug and healthcare use) for mother and child from enrolment until discharge, will be compared to incremental effects measured as prolongation of gestation Cost-effectiveness long-term: societal costs (based on drug and healthcare use, and social insurance transactions) for mother and child from enrolment until two years postpartum, will be compared to incremental effects measured as prolongation of gestation and health-related quality of life |
From birth to two years post partum
|
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Risk of autism spectrum disorder
Временное ограничение: At two years corrected age
|
Risk of autism spectrum disorder (evaluated by the Modified Checklist for Autism in Toddlers, Revised (M-CHAT/R); 20 questions resulting in score 0-20 where 0-2 indicates no risk, 3-7 moderate risk and 8-20 high risk for autism). |
At two years corrected age
|
|
Cognitive development of the child
Временное ограничение: At two years corrected age
|
Developmental screening (based on parental questionnaire Ages and Stages Questionnaire, Third Edition 24-months (ASQ-3);questions covering five key developmental domains; communication, gross motor, fine motor, problem-solving and personal-social skills; answers scored from 0-60 with age-specific cut-off levels at -2 and -1SD indicating clear or suspect developmental delay) |
At two years corrected age
|
|
Cognitive development of the child
Временное ограничение: At two years corrected age
|
Comprehensive developmental assessment (evaluated by the Bayley Scales of Infant Development-4 (BSID-4), with main scores for motor, language and cognitive function. Results expressed as age-corrected developmental scores in each domain with clear developmental delay at scores < 70 (-2SD) and suspect developmental delay at scores < 85 (-1SD). |
At two years corrected age
|
Соавторы и исследователи
Спонсор
Соавторы
Следователи
- Главный следователь: Lina Bergman, Associate professor, Sahlgrenska University Hospital
Публикации и полезные ссылки
Общие публикации
- Brownfoot FC, Hastie R, Hannan NJ, Cannon P, Tuohey L, Parry LJ, Senadheera S, Illanes SE, Kaitu'u-Lino TJ, Tong S. Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction. Am J Obstet Gynecol. 2016 Mar;214(3):356.e1-356.e15. doi: 10.1016/j.ajog.2015.12.019. Epub 2015 Dec 22.
- Chappell LC, Cluver CA, Kingdom J, Tong S. Pre-eclampsia. Lancet. 2021 Jul 24;398(10297):341-354. doi: 10.1016/S0140-6736(20)32335-7. Epub 2021 May 27.
- Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013 Sep;170(1):1-7. doi: 10.1016/j.ejogrb.2013.05.005. Epub 2013 Jun 7.
- Cluver CA, Hiscock R, Decloedt EH, Hall DR, Schell S, Mol BW, Brownfoot F, Kaitu'u-Lino TJ, Walker SP, Tong S. Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial. BMJ. 2021 Sep 22;374:n2103. doi: 10.1136/bmj.n2103.
- Hu J, Zhang J, Zhu B. Protective effect of metformin on a rat model of lipopolysaccharide-induced preeclampsia. Fundam Clin Pharmacol. 2019 Dec;33(6):649-658. doi: 10.1111/fcp.12501. Epub 2019 Aug 13.
- Wang F, Cao G, Yi W, Li L, Cao X. Effect of Metformin on a Preeclampsia-Like Mouse Model Induced by High-Fat Diet. Biomed Res Int. 2019 Dec 7;2019:6547019. doi: 10.1155/2019/6547019. eCollection 2019.
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Урогенитальные заболевания
- Женские мочеполовые заболевания и осложнения беременности
- Масса тела
- Акушерские роды, преждевременные роды
- Осложнения акушерских родов
- Осложнения беременности
- Гипертония, вызванная беременностью
- Патологические состояния, признаки и симптомы
- Признаки и симптомы
- Преждевременные роды
- Преэклампсия
- Вес при рождении
- Органические химические вещества
- Бигуаниды
- Гуанидины
- Амидины
- Метформин
Другие идентификационные номера исследования
- EU Trial nr: 2022-502707-2-00
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
Metadata and statistical code will be published in public repositories upon release of the trial's primary results. Deidentified data may be shared upon reasonable request following a written application including a research proposal and ethical approval, in accordance with applicable ethical and legal requirements.
We plan to share data with similar ongoing or planned trials in South Africa and The Netherlands.
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
продукт, произведенный в США и экспортированный из США.
Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .