xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06033131</url>
    </required_header>
    <id_info>
      <org_study_id>EU Trial nr: 2022-502707-2-00</org_study_id>
      <nct_id>NCT06033131</nct_id>
    </id_info>
    <brief_title>PI4 - A Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia</brief_title>
    <acronym>PI4</acronym>
    <official_title>Preeclampsia Intervention 4 - A Triple Blind Phase III Randomised Controlled Trial Assessing Metformin to Prolong Gestation in Preterm Preeclampsia</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Lina Bergman</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>The Swedish Research Council</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Sahlgrenska University Hospital, Sweden</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Preterm preeclampsia is a severe condition for both the mother and the fetus. Currently, the&#xD;
        only treatment available to stop disease progression is termination/delivery of the fetus and&#xD;
        placenta. Therefore, preterm preeclampsia carries the highest rates of neonatal morbidity and&#xD;
        mortality due to iatrogenic preterm birth. There is evidence suggesting metformin, a drug&#xD;
        commonly used to treat diabetes in and outside pregnancy, may be able to counter the&#xD;
        pathophysiology of preeclampsia, raising the possibility that it could be used to treat the&#xD;
        condition. This multi centre double blind randomised controlled trial aims to investigate if&#xD;
        metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a&#xD;
        Swedish setting.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Preeclampsia is globally responsible for 60,000 maternal deaths per year, and far greater&#xD;
        numbers of fetal losses. Preterm preeclampsia is a severe variant with the highest rates of&#xD;
        neonatal morbidity and mortality due to iatrogenic preterm birth (clinicians are forced to&#xD;
        deliver the baby preterm for maternal or fetal health reasons).&#xD;
  &#xD;
        There is preclinical evidence suggesting metformin, a drug commonly used to treat diabetes in&#xD;
        and outside pregnancy, may be able to counter the pathophysiology of preeclampsia, raising&#xD;
        the possibility that it could be used to treat the condition.&#xD;
  &#xD;
        Previous research from the Preeclampsia Intervention 2 trial (PI2) show that metformin was&#xD;
        able to delay delivery in early preterm preeclampsia. Metformin extended release (ER) was&#xD;
        associated with a median 7.6-day prolongation of pregnancy (geometric mean ratio (GMR) 1.39&#xD;
        (95% CI 0.99 to 1.96) P=0.057).Trends towards increased birthweight (mean difference 110gm&#xD;
        (95%CI -80 to 300), a decreased length of stay at the neonatal intensive care unit (median&#xD;
        difference 5.0 days less; GMR 0.86, 95% CI 0.62 to 1.2) and a shorter period of admission in&#xD;
        any neonatal ward (median difference 12.0 days less; GMR 0.82, 95% CI 0.57 to 1.18) in the&#xD;
        metformin ER group were found. Importantly, while gastrointestinal side effects were common,&#xD;
        no serious adverse events related to trial medications were observed.&#xD;
  &#xD;
        The PI 2 trial has shown that metformin may be a disease modifying treatment for preterm&#xD;
        preeclampsia. The trial is being repeated in a larger scale in the PI3 trial in South Africa&#xD;
        to also assess neonatal outcomes. In Sweden, the demographics of the population are different&#xD;
        and expectant management of preeclampsia allows for the women to reach 37 weeks of gestation&#xD;
        as opposed to 34 weeks of gestation in the PI2 trial. This trial aims to investigate if&#xD;
        metformin can prolong gestation, lower neonatal length of stay and increase birthweight in a&#xD;
        Swedish setting.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2027</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Pregnancy prolongation</measure>
      <time_frame>From randomisation to delivery, measured in days and hours, up to 105 days</time_frame>
      <description>Length of pregnancy from diagnosis of preeclampsia to delivery</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Time for neonatal care</measure>
      <time_frame>From birth to discharge from neonatal care, measured in days and hours, up to 126 days</time_frame>
      <description>Time for neonatal care from birth to discharge</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Neonatal birth weight</measure>
      <time_frame>At birth</time_frame>
      <description>Birth wight measured in grams</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">294</enrollment>
    <condition>Preeclampsia</condition>
    <arm_group>
      <arm_group_label>Metformin ER</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Metformin ER oral tablet 500 mg three times daily and increased to one gram (two tablets) three times daily as tolerated.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>1 placebo tablet three times daily and increased to 2 placebo tablets three times daily as tolerated.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Metformin ER</intervention_name>
      <description>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.</description>
      <arm_group_label>Metformin ER</arm_group_label>
      <other_name>Glucophage SR 500 mg prolonged release tablets</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>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.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  A diagnosis of preeclampsia (defined as hypertension in combination with significant&#xD;
               proteinuria (albumin/creatinine ratio &gt;8 mg/mmol, protein/creatinine ratio&gt;30 mg/mmol&#xD;
               or &gt;2+ protein on a urinary dipstick) has been made by the attending clinician&#xD;
  &#xD;
            -  The managing clinicians have made the assessment to proceed with expectant management.&#xD;
  &#xD;
            -  The subject has given written consent to participate in the study.&#xD;
  &#xD;
            -  The woman must be 18 years of age or older&#xD;
  &#xD;
            -  The gestational age is between 22+0 weeks to 33+6 weeks with a viable fetus&#xD;
  &#xD;
            -  The woman carries a singleton pregnancy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Contraindications to treatment with metformin as outlined in SmPC&#xD;
  &#xD;
            -  Contraindications for expectant management of preeclampsia such as an immediate&#xD;
               indication for delivery according to SFOG guidelines for preeclampsia&#xD;
               (https://www.sfog.se/media/338533/pe-riktlinje-230214.pdf).&#xD;
  &#xD;
            -  Type 1 Diabetes Mellitus&#xD;
  &#xD;
            -  Current use of metformin&#xD;
  &#xD;
            -  Concomitant medications that are not compatible with metformin such as glyburide,&#xD;
               furosemide or cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine,&#xD;
               quinine, ranitidine, triamterene, trimethoprim and vancomycin)&#xD;
  &#xD;
            -  Known or suspected allergies against metformin&#xD;
  &#xD;
            -  Reluctance or language difficulties that result in difficulty understanding the&#xD;
               meaning of study participation&#xD;
  &#xD;
            -  Unable to understand the informed consent process&#xD;
  &#xD;
            -  Previous participation in the study&#xD;
  &#xD;
            -  Established fetal compromise that necessitates imminent delivery (including planned&#xD;
               delivery after 48 hours of corticosteroid treatment). This will be decided by the&#xD;
               clinical team before expectant management is offered to the patient.&#xD;
  &#xD;
            -  Suspicion of a major known fetal anomaly or malformation.&#xD;
  &#xD;
            -  Renal disease or dysfunction, suggested by a creatinine level greater than or equal to&#xD;
               125 µmol/L or rapidly declining renal function&#xD;
  &#xD;
            -  Known acute or chronic metabolic acidosis, including diabetic ketoacidosis&#xD;
  &#xD;
            -  Not suitable for inclusion by the opinion of the investigator&#xD;
        </textblock>
      </criteria>
      <gender>Female</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Lina Bergman, Associate Pr</last_name>
      <phone>+463134307</phone>
      <email>lina.bergman@obgyn.gu.se</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Pia Gudmundsson, PhD</last_name>
      <email>pia.gudmundsson@obgyn.gu.se</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Falu Lasarett</name>
        <address>
          <city>Falun</city>
          <zip>79129</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Susanne Hesselman, PhD</last_name>
        <phone>004623492351</phone>
        <email>susanne.hesselman@regiondalarna.se</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Sahlgrenska University Hospital</name>
        <address>
          <city>Gothenburg</city>
          <zip>416 85</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Lina Bergman, Associate professor</last_name>
        <phone>+463134307</phone>
        <email>lina.bergman@obgyn.gu.se</email>
      </contact>
      <contact_backup>
        <last_name>Pia Gudmundsson, PhD</last_name>
        <email>pia.gudmundsson@obgyn.gu.se</email>
      </contact_backup>
    </location>
    <location>
      <facility>
        <name>Malmö University Hospital</name>
        <address>
          <city>Malmö</city>
          <zip>21428</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Simon Timpka, associate Professor</last_name>
        <phone>0046462220000</phone>
        <email>simon.timpka@med.lu.se</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Karolinska University Hospital Huddinge</name>
        <address>
          <city>Stockholm</city>
          <zip>14157</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Anna Sandström, Associate Professor</last_name>
        <phone>0046739829820</phone>
        <email>anna.sandstrom@ki.se</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Karolinska University Hospital Solna</name>
        <address>
          <city>Stockholm</city>
          <zip>17176</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Anna Sandström, Associate Professor</last_name>
        <phone>0046739829820</phone>
        <email>anna.sandstrom@ki.se</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Uppsala University Hospital</name>
        <address>
          <city>Uppsala</city>
          <zip>75237</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <contact>
        <last_name>Anna-Karin Wikström, Professor</last_name>
        <phone>0046184710000</phone>
        <email>anna-karin.wikstrom@kbu.uu.se</email>
      </contact>
    </location>
    <location_countries>
      <country>Sweden</country>
    </location_countries>
    <reference>
      <citation>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.</citation>
      <PMID>34051884</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>23746796</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>34551918</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>26721779</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>31334867</PMID>
    </reference>
    <reference>
      <citation>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.</citation>
      <PMID>31886236</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 28, 2023</study_first_submitted>
    <study_first_submitted_qc>September 10, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Sahlgrenska University Hospital, Sweden</investigator_affiliation>
      <investigator_full_name>Lina Bergman</investigator_full_name>
      <investigator_title>Senior consultant, Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Preeclampsia</keyword>
    <keyword>Metformin</keyword>
    <keyword>Preterm birth</keyword>
    <keyword>Prolongation</keyword>
    <keyword>Birth weight</keyword>
    <keyword>Length of stay in neonatal care</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Pre-Eclampsia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Metformin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We plan to share data with similar ongoing or planned trials in South Africa and The Netherlands.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06033131
  org study id: EU Trial nr: 2022-502707-2-00
  nct id: NCT06033131
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  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
        Swedish setting.
  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 Sweden, 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
        Swedish setting.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: Pregnancy prolongation
  time frame: From randomisation to delivery, measured in days and hours, up to 105 days
  description: Length of pregnancy from diagnosis of preeclampsia to delivery
  measure: Time for neonatal care
  time frame: From birth to discharge from neonatal care, measured in days and hours, up to 126 days
  description: Time for neonatal care from birth to discharge
  measure: Neonatal birth weight
  time frame: At birth
  description: Birth wight measured in grams
  arm group label: Metformin ER
  arm group type: Active Comparator
  description: Metformin ER oral tablet 500 mg three times daily and increased to one gram (two tablets) three times daily as tolerated.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: 1 placebo tablet three times daily and increased to 2 placebo tablets three times daily as tolerated.
  intervention type: Drug
  intervention name: Metformin ER
  description: 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.
  arm group label: Metformin ER
  other name: Glucophage SR 500 mg prolonged release tablets
  intervention type: Drug
  intervention name: Placebo
  description: 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.
  arm group label: Placebo
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lina Bergman, Associate Pr
  phone: +463134307
  email: lina.bergman@obgyn.gu.se
  last name: Pia Gudmundsson, PhD
  email: pia.gudmundsson@obgyn.gu.se
  facility: 
  contact: 
  facility: 
  contact: 
  contact backup: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: Sweden
  citation: 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.
  PMID: 34051884
  citation: 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.
  PMID: 23746796
  citation: 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.
  PMID: 34551918
  citation: 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.
  PMID: 26721779
  citation: 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.
  PMID: 31334867
  citation: 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.
  PMID: 31886236
  responsible party type: Sponsor-Investigator
  investigator affiliation: Sahlgrenska University Hospital, Sweden
  investigator full name: Lina Bergman
  investigator title: Senior consultant, Associate Professor
  mesh term: Pre-Eclampsia
  mesh term: Metformin
  sharing ipd: Yes
  ipd description: We plan to share data with similar ongoing or planned trials in South Africa and The Netherlands.