이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

PI4 - 조기 자간전증의 임신 기간을 연장하기 위해 메트포르민을 평가하는 시험 (PI4)

2026년 9월 23일 업데이트: Lina Bergman

자간전증 중재 4 - 조기 자간전증의 임신 기간을 연장하기 위해 메트포르민을 평가하는 삼중 맹검 제3상 무작위 대조 시험

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.

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

294

단계

  • 3단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 연락처 백업

연구 장소

  • 노르웨이
      • Lørenskog, 노르웨이, N-1474
        • 모병
        • Akershus University Hospital
        • 연락하다:
        • 수석 연구원:
          • Camilla Haavaldsen, PhD
      • Oslo, 노르웨이, 0372
        • 모병
        • Oslo University Hospital
        • 연락하다:
          • Trond Michelsen, Professor
          • 전화번호: 0047-23072619
          • 이메일: trmi1@ous-hf.no
        • 수석 연구원:
          • Ingvil Krarup Sørbye, Professor
  • 스웨덴
      • Borås, 스웨덴, 50455
        • 모병
        • Södra Älvsborgs Hospital
        • 연락하다:
        • 수석 연구원:
          • Lina Bergman, Associate Professor
      • Falun, 스웨덴, 79129
      • Gothenburg, 스웨덴, 416 85
      • Linköping, 스웨덴, 581 85
      • Lund, 스웨덴, 221 85
        • 모병
        • Skåne University Hospital
        • 연락하다:
        • 연락하다:
      • Malmö, 스웨덴, 205 02
        • 모병
        • Skåne University Hospital
        • 연락하다:
      • Skövde, 스웨덴, 549 49
        • 모병
        • Skaraborg Hospital
        • 연락하다:
      • Stockholm, 스웨덴, 17176
        • 모병
        • Karolinska University Hospital Solna
        • 연락하다:
        • 연락하다:
      • Stockholm, 스웨덴, 182 88
      • Stockholm, 스웨덴, 14157
        • 모병
        • Karolinska University Hospital Huddinge
        • 연락하다:
        • 연락하다:
      • Trollhättan, 스웨덴, 461 74
        • 모병
        • Norra Älvsborgs County Hospital
        • 수석 연구원:
          • Lina Bergman, Associate Professor
        • 연락하다:
      • Umeå, 스웨덴, 901 85
        • 모병
        • Norrland´s University Hospital
        • 연락하다:
        • 수석 연구원:
          • Marie-Therese Vinnars, PhD
      • Uppsala, 스웨덴, 75237
        • 모병
        • Uppsala University Hospital
        • 연락하다:
      • Västerås, 스웨덴, 72335
        • 모병
        • Västmanlands Hospital Västerås
        • 연락하다:
        • 수석 연구원:
          • Linda Lindström, PhD
  • 핀란드
      • Helsinki, 핀란드, 00290
        • 모병
        • Helsinki University Hospital
        • 연락하다:
        • 수석 연구원:
          • Pia Villa, Associate Professor
      • Tampere, 핀란드, 33520
        • 모병
        • Tampere University Hospital
        • 연락하다:
        • 수석 연구원:
          • Hannele Laivuori, Professor

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

여성

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 삼루타

무기와 개입

참가자 그룹 / 팔
개입 / 치료
활성 비교기: Metformin ER

Metformin ER oral tablet 500 mg three times daily and increased to one gram (two tablets) three times daily as tolerated.
의약품: Metformin ER

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.

다른 이름들:
  • Glucophage SR 500 mg 연장 방출 정제
위약 비교기: Placebo

1 placebo tablet three times daily and increased to 2 placebo tablets three times daily as tolerated.
의약품: Placebo

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.

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Pregnancy prolongation
기간: From randomisation to delivery, measured in days and hours, up to 105 days

Length of pregnancy from diagnosis of preeclampsia to delivery
From randomisation to delivery, measured in days and hours, up to 105 days

2차 결과 측정

결과 측정
측정값 설명
기간
Time for neonatal care
기간: From birth to discharge from neonatal care, measured in days and hours, up to 126 days

Time for neonatal care from birth to discharge
From birth to discharge from neonatal care, measured in days and hours, up to 126 days
Neonatal birth weight
기간: At birth

Birth wight measured in grams
At birth

기타 결과 측정

결과 측정
측정값 설명
기간
Occurrence of maternal death
기간: Registered from inclusion to two month post partum

Occurrence of maternal death
Registered from inclusion to two month post partum
Occurrence of Eclampsia
기간: Registered from inclusion to two month post partum

Occurrence of Eclampsia
Registered from inclusion to two month post partum
Occurrence of Cerebral vascular event
기간: Registered from inclusion to two month post partum

Occurrence of Cerebral vascular event
Registered from inclusion to two month post partum
Occurrence of posterior reversible encephalopathy syndrome
기간: Registered from inclusion to two month post partum

Occurrence of posterior reversible encephalopathy syndrome
Registered from inclusion to two month post partum
Occurrence of pulmonary edema
기간: 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
기간: Registered from inclusion to two month post partum

Occurrence of left ventricular failure
Registered from inclusion to two month post partum
Occurrence of renal dialysis
기간: Registered from inclusion to two month post partum

Occurrence of renal dialysis
Registered from inclusion to two month post partum
Occurrence of renal failure
기간: Registered from inclusion to two month post partum

Occurrence of renal failure:≥ 90 µmol/L or no urinary output for 6 hours
Registered from inclusion to two month post partum
Occurrence of elevated liver transaminases
기간: Registered from inclusion to two month post partum

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
Occurrence of HELLP syndrome
기간: Registered from inclusion to two month post partum

Occurrence of HELLP (Haemolysis, elevated liver enzymes and low platelets) syndrome
Registered from inclusion to two month post partum
Occurrence of thrombocytopenia
기간: Registered from inclusion to two month post partum

Occurrence of thrombocytopenia (platelets <100 X 109/L)
Registered from inclusion to two month post partum
Occurrence of liver haematoma or rupture
기간: Registered from inclusion to two month post partum

Occurrence of liver haematoma or rupture
Registered from inclusion to two month post partum
Occurrence of admission to an intensive care unit
기간: Registered from inclusion to two month post partum

Occurrence of admission to an intensive care unit
Registered from inclusion to two month post partum
Occurrence of severe hypertension
기간: Registered from inclusion to two month post partum

Occurrence of severe hypertension (BP>160/110 mm Hg)
Registered from inclusion to two month post partum
Occurrence of disseminated intravascular coagulation
기간: Registered from inclusion to two month post partum

Occurrence of disseminated intravascular coagulation
Registered from inclusion to two month post partum
Occurrence of caesarean section
기간: At birth

Occurrence of caesarean section
At birth
Occurrence of major postpartum hemorrhage
기간: At birth

Occurrence of major postpartum hemorrhage (>1000 ml)
At birth
Occurrence of thromboembolic disease
기간: 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
Duration of maternal postpartum hospital stay
기간: Registered from birth to hospital discharge

Duration of maternal postpartum hospital stay (days)
Registered from birth to hospital discharge
Number of antihypertensive drugs
기간: At discharge

Number of antihypertensive drugs at discharge after delivery
At discharge
Duration of antihypertensive medication
기간: From inclusion to two month postpartum

Duration of antihypertensive medication (days)
From inclusion to two month postpartum
Occurrence of intrauterine fetal demise
기간: From inclusion to birth

Occurrence of intrauterine fetal demise
From inclusion to birth
Occurrence of neonatal death
기간: From inclusion to two month post partum

Occurrence of neonatal death
From inclusion to two month post partum
Occurrence of growth restriction at birth
기간: At birth

Occurrence of growth restriction at birth (less than 2 standard deviations from median weight from Swedish birth weight growth curves).
At birth
Occurrence of grade 3 or 4 intraventricular hemorrhage
기간: Registered from birth to two month post partum

Occurrence of grade 3 or 4 intraventricular hemorrhage
Registered from birth to two month post partum
Occurrence of necrotizing enterocolitis
기간: Registered from birth to two month post partum

Occurrence of necrotizing enterocolitis
Registered from birth to two month post partum
Occurrence of reversed a-wave in the ductus venosus
기간: 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
Occurrence of persistent reversed flow in the umbilical artery
기간: Registered from inclusion to birth

Occurrence of persistent reversed flow in the umbilical artery
Registered from inclusion to birth
Occurrence of redistribution in the middle cerebral artery
기간: Registered from birth to two month post partum

Occurrence of redistribution in the middle cerebral artery
Registered from birth to two month post partum
Occurrence of low APGAR score
기간: At birth

Occurrence of low APGAR score, defined as less than 4 at 5 minutes
At birth
Occurrence of umbilical artery pH below 7.1
기간: At birth

Occurrence of umbilical artery pH below 7.1
At birth
Occurrence of invasive ventilation, intubation and mechanical ventilation or non-invasive ventilatione outcome
기간: 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
Occurrence of grade III/IV hyaline membrane disease
기간: Registered from birth to two month post partum

Occurrence of grade III/IV hyaline membrane disease
Registered from birth to two month post partum
Occurrence of surfactant use
기간: Registered from birth to two month post partum

Occurrence of surfactant use
Registered from birth to two month post partum
Occurrence of retinopathy of prematurity
기간: Registered from birth to two month post partum

Occurrence of retinopathy of prematurity
Registered from birth to two month post partum
Occurrence of neonatal sepsis
기간: Registered from birth to two month post partum

Occurrence of neonatal sepsis
Registered from birth to two month post partum
Tolerability and safety
기간: 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
Tolerability and safety
기간: From inclusion to birth

Occurrence of lactic acidosis (blood pH< 7.35 or blood lactate> 5 mM)
From inclusion to birth
Tolerability and safety
기간: From inclusion to birth

Drug adherence (measured by treatment diary)
From inclusion to birth
Pre-eclampsia-related biomarkers
기간: 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
Gut and vaginal microbiome composition
기간: From inclusion to two years post partum

Omics-based analysis of the microbiome
From inclusion to two years post partum
Breastfeeding initiation
기간: From birth to two month postpartum

Breastfeeding initiation (measured by unvalidated breastfeeding questionnaire with no score)
From birth to two month postpartum
Depressive symptoms
기간: 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
Self-esteem
기간: 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
Perceived stress
기간: 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
Breastfeeding self-efficacy
기간: 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
Health-related quality of life
기간: 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
Parental-infant bonding
기간: 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
Health economic outcomes
기간: 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
Risk of autism spectrum disorder
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Lina Bergman

협력자

The Swedish Research Council

수사관

  • 수석 연구원: Lina Bergman, Associate professor, Sahlgrenska University Hospital

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2024년 1월 19일

기본 완료 (추정된)

2027년 12월 31일

연구 완료 (추정된)

2029년 12월 31일

연구 등록 날짜

최초 제출

2023년 8월 28일

QC 기준을 충족하는 최초 제출

2023년 9월 10일

처음 게시됨 (실제)

2023년 9월 13일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 28일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 23일

마지막으로 확인됨

2026년 8월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • EU Trial nr: 2022-502707-2-00

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

예

IPD 계획 설명

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.

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

미국에서 제조되어 미국에서 수출되는 제품

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이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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