Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
360
Countries
3
Sites
14
Preeclampsia
To examine whether 3 grams of metformin ER daily can prolong gestation in pregnancies complicated by preterm preeclampsia diagnosed 22+0–33+6 weeks in women undergoing expectant management, compared to placebo.
Key facts
- Sponsor
- Vastra Gotalandsregionen, University Of Gothenburg
- Participant type
- Pediatric, Patients
- Age range
- 0-17 years, 18-64 years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
- Trial duration
- 7 Feb 2024 → ongoing
- Decision date (initial)
- 2026-03-04
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
External identifiers
- EU CT number
- 2022-502707-29-00
- ClinicalTrials.gov
- NCT06033131
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To examine whether 3 grams of metformin ER daily can prolong gestation in pregnancies complicated by preterm preeclampsia diagnosed 22+0–33+6 weeks in women undergoing expectant management, compared to placebo.
Secondary objectives 2
- To determine whether 3 grams of metformin ER daily can reduce the time from birth to discharge from neonatal care in neonates born to women with preterm preeclampsia diagnosed at 22+0–33+6 weeks undergoing expectant management, compared to placebo.
- To determine whether 3 grams of metformin ER daily can increase neonatal birthweight of neonates born to women with preterm preeclampsia diagnosed at 22+0–33+6 weeks undergoing expectant management, compared to placebo.
Conditions and MedDRA coding
Preeclampsia
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 6
- • A diagnosis of preeclampsia has been made by the attending clinician
- • The managing clinicians have made the assessment to proceed with expectant management and that delivery is not expected within 48 hours
- • 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 13
- • There are contraindications to treatment with metformin as outlined in SmPC (Attachment E)
- • 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.
- Diabetes type 1
- • 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
- • Contraindications for expectant management of preeclampsia such as an immediate indication for delivery according to Nordic guidelines.
- Current use of metformin
- • Known or suspected allergies against metformin
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- The primary endpoint is prolongation of gestation, defined as days and hours from randomisation to delivery. Prolongation of gestation in pregnancies with intrauterine fetal demise will be considered as interval censored between time from randomisation to last visit preceding delivery (where the baby was known to be alive) and time from randomisation to delivery.
Secondary endpoints 2
- Length of neonatal stay, defined as days and hours from birth to discharge from neonatal care, including both hospital and home-based care. Length of neonatal stay will be as zero if the infant was not admitted to neonatal care.
- Neonatal birthweight, in grams.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Glucophage SR 500mg prolonged release tablet
PRD338487 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- PROLONGED-RELEASE TABLET
- Route of administration
- ORAL
- Max daily dose
- 3 g gram(s)
- Max total dose
- 315 g gram(s)
- Max treatment duration
- 15 Week(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- PL 11648/0054
- MA holder
- MERCK SERONO LIMITED
- MA country
- United Kingdom
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Repacking of the product
Placebo 1
Glucophage XR 500 mg RM Placebo
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Vastra Gotalandsregionen
- Sponsor organisation
- Vastra Gotalandsregionen
- Address
- Regionens Hus
- City
- Vänersborg
- Postcode
- 462 80
- Country
- Sweden
Scientific contact point
- Organisation
- Vastra Gotalandsregionen
- Contact name
- Lina Bergman
Public contact point
- Organisation
- Vastra Gotalandsregionen
- Contact name
- Lina Bergman
University Of Gothenburg
- Sponsor organisation
- University Of Gothenburg
- Address
- P. O. Box 100
- City
- Gothenburg
- Postcode
- 405 30
- Country
- Sweden
Scientific contact point
- Organisation
- Vastra Gotalandsregionen
- Contact name
- Lina Bergman
Public contact point
- Organisation
- Vastra Gotalandsregionen
- Contact name
- Lina Bergman
Sponsor responsibilities
- Article 77 compliance
- Vastra Gotalandsregionen
- Contact point sponsor
- Vastra Gotalandsregionen
- Article 77 implementation
- Vastra Gotalandsregionen
Locations
3 EU/EEA countries · 14 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Finland | Ongoing, recruiting | 50 | 2 |
| Norway | Authorised, recruitment pending | 16 | 2 |
| Sweden | Ongoing, recruiting | 294 | 10 |
| Rest of world | — | 0 | — |
Investigational sites
Pirkanmaan hyvinvointialue
Gynekologien monityötila, Elamanaukio 2, 33520, Tampere
HUS-yhtymae
Synnytys- ja naistentautien osasto, Haartmaninkatu 2, P. O. Box 140, Helsinki
Akershus University Hospital
Kvinneklinikken, Observasjonsavdelingen, Sykehusveien 25, 1474, Loerenskog
Oslo Universitetssykehus HF
Förlossningsavdelningen, Sognsvannsveien 20, 0372, Oslo
Danderyds Sjukhus AB
Kvinnokliniken, Danderyds sjukhus, Morbygardsvagen 88, 182 88, Danderyd
Region Oestergoetland
Kvinnokliniken, Universitetssjukhuset Linköping, Universitetssjukhuset I, 58185, Linkoping
Uppsala University Hospital
Kvinnosjukvård, Kvinnors och barns hälsa, Akademiska sjukhuset, 75185 Uppsala, Akademiska Sjukhuset, 751 85, Uppsala
Karolinska University Hospital
ME Graviditet och förlossning, Huddinge sjukhus, 14186 Stockholm, Halsovagen, Flemingsberg, Huddinge
Region Skane - Skanes Universitetssjukhus
Kvinnosjukvård, Klinikgatan 12, 22185 Lund, Entregatan 7, Lunds Allhelgonafors, Lund
Region Skane - Skanes Universitetssjukhus
Kvinnosjukvård, Jan Waldenströms gata 47, 20502 Malmö, St. Johns, Fritz Bauers Gata 5, Malmo
Karolinska University Hospital
ME Graviditet och Förlossning, Akademiska Stråket 14, F5:86, 17176 Stockholm, Eugeniavagen 3, 171 64, Solna
Sahlgrenska University Hospital-Vastra Gotalandsregionen
Kvinnosjukvård, Diagnosvägen 15, 41685 Gothenburg, Diagnosvagen 11, Harlanda, Gothenburg
Region Dalarna
Kvinnokliniken, Falu lasarett, Lasarettsvägen 10, 79182 Falun, Vasagatan 27, Falu Kristine, Falun
Region Vaesterbotten
Institutionen för klinisk vetenskap, Obstetrik och Gynekologi, Koksvagen 11, Alidhem, Umea
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Finland | 2026-04-24 | 2026-05-04 | |||
| Sweden | 2024-02-07 | 2024-02-07 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 25 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol appendix A_2022_502707_29_00 | 4.1 |
| Protocol (for publication) | D1_Protocol appendix B_2022_502707_29_00 | 2 |
| Protocol (for publication) | D1_Protocol appendix C_2022_502707_29_00 | 4 |
| Protocol (for publication) | D1_Protocol appendix D_2022_502707_29_00 | 4 |
| Protocol (for publication) | D1_Protocol appendix E_2022_502707_29_00 | 2 |
| Protocol (for publication) | D1_Protocol appendix F_2022_502707_29_00 | 4 |
| Protocol (for publication) | D1_Protocol_2022_502707_29_00 | 7.1 |
| Protocol (for publication) | D2_Protocol_appendix H_2022_502707_29_00_FIN | 1 |
| Protocol (for publication) | D4_Protocol_appendix G_2022_502707_29_00 | 1 |
| Recruitment arrangements (for publication) | K1_ Rekryteringsforfarande_2022_502707_29_00 | 1 |
| Recruitment arrangements (for publication) | K1_ Rekryteringsmaterial_2022_502707_29_00 | 3 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_FI_2022_502707_29_00 | 1 |
| Recruitment arrangements (for publication) | K1_Rekryteringsforfarande_NO_2022_502707_29_00 | 2 |
| Recruitment arrangements (for publication) | K2_Rekryteringmaterial_NO_2022_502707_29_00 | 1 |
| Subject information and informed consent form (for publication) | K2_Forsokspersonsinformation och samtycke uppfoljning av barn_2022_502707_29_00 | 5 |
| Subject information and informed consent form (for publication) | K2_Forsokspersonsinformation och samtycke_2022_502707_29_00 | 5.1 |
| Subject information and informed consent form (for publication) | L1_Forskspersoninformasjon og samtykke - barn_NO_2022_502707_29_00 | 8 |
| Subject information and informed consent form (for publication) | L1_Forskspersoninformasjon og samtykke for fremtidig forskning_NO_2022_502707_29_00 | 1 |
| Subject information and informed consent form (for publication) | L1_Forskspersoninformasjon og samtykke for fremtidig forskning-Barn_NO_2022_502707_29_00 | 1 |
| Subject information and informed consent form (for publication) | L1_Forskspersoninformasjon og samtykke_NO_2022_502707_29_00 | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_study participant_FI_2022_502707_29_00_public | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_study participant_FI_sv_2022_502707_29_00_public | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | G2_SmPC Glucophage SR UK | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol_synopsis_SE_2022_502707_29_00 | 4 |
| Synopsis of the protocol (for publication) | D2_Protocol_synopsis_NO_2022_502707_29_00 | 1 |
Application history
12 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-03-10 | Sweden | Acceptable 2023-05-23
|
2023-05-31 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-09-26 | Sweden | Acceptable 2023-10-24
|
2023-11-08 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-01-09 | Sweden | Acceptable 2024-03-20
|
2024-03-21 |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-03-28 | Sweden | Acceptable | 2024-05-13 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2024-11-06 | Sweden | Acceptable 2024-12-12
|
2024-12-17 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-02-03 | Sweden | Acceptable 2025-02-25
|
2025-03-17 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2025-11-20 | Sweden | Acceptable 2025-12-17
|
2025-12-17 |
| 8 | SUBSEQUENT ADDITION OF MSC | APP-8 | 2025-12-19 | 2026-03-04 | ||
| 9 | SUBSEQUENT ADDITION OF MSC | APP-9 | 2025-12-19 | 2026-03-27 | ||
| 10 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-03-30 | Sweden | 2026-03-30 | |
| 11 | SUBSTANTIAL MODIFICATION | SM-7 | 2026-04-09 | Acceptable | 2026-05-22 | |
| 12 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2026-05-26 | 2026-05-26 |