Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruiting
Participants planned
180
Countries
1
Sites
8
HELLP syndrome
To assess whether metformin, compared to placebo, prolongs gestation (for at least 5 more days) in pregnant individuals with preterm PE.
Key facts
- Sponsor
- Amsterdam UMC
- Participant type
- Patients
- Age range
- 18-64 years
- Gender
- Female
- Therapeutic area
- Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
- Trial duration
- 25 Aug 2025 → ongoing
- Decision date (initial)
- 2024-09-24
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- ZonMw
External identifiers
- EU CT number
- 2023-510382-10-00
- WHO UTN
- U1111-1303-8616
- ClinicalTrials.gov
- NCT06452498
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy
To assess whether metformin, compared to placebo, prolongs gestation (for at least 5 more days) in pregnant individuals with preterm PE.
Secondary objectives 1
- To determine whether metformin, compared to placebo, can improve composite maternal, fetal, and neonatal outcomes.
Conditions and MedDRA coding
HELLP syndrome
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | LLT | 10036488 | Pre-eclampsia or eclampsia superimposed on pre-existing hypertension complicating pregnancy childb | 10036585 |
| 20.0 | HLT | 10020776 | Hypertension associated disorders of pregnancy | 10036585 |
| 20.0 | LLT | 10071421 | Fetal exposure during pregnancy | 10022117 |
| 20.0 | PT | 10036485 | Pre-eclampsia | 100000004868 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Treatment phase Metformin vs placebo
|
Randomised Controlled | Double | [{"id":186707,"code":5,"name":"Carer"},{"id":186705,"code":1,"name":"Subject"},{"id":186706,"code":2,"name":"Investigator"}] | Arm 1: Metformin Arm 2: Placebo |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 8
- Aged 18 years or older
- Singleton pregnancy
- Gestational age between 23+0 and 31+6 weeks
- Estimated fetal weight >400 grams
- There is no clear indication (maternal or fetal) or intention, by both the treating multidisciplinary team and the patient after counseling, to immediately deliver (or directly after corticosteroid administration) or to terminate the pregnancy otherwise
- A diagnosis of PE, according to PI-NL criteria
- Ability to understand English or Dutch
- Ability and willingness to provide written informed consent
Exclusion criteria 8
- Aged <18 years
- Multiple pregnancy
- Current use of metformin or a clinical indication for the use of metformin
- A decision for immediate delivery (including cases where corticosteroids are administered with planned delivery directly after completion of treatment) or termination of pregnancy (e.g., due to disease severity in the patient combined with a dismal prognosis for the fetus), as made by the treating multidisciplinary team and the parent(s)
- Contraindication(s) for use of metformin
- Use of drugs that might interact with metformin
- Suspicion of a major fetal anomaly and/or chromosomal abnormality
- Unable or unwilling to (completely) understand or provide informed consent, due to language, culture, or other barriers
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Gestational prolongation (in days)
Secondary endpoints 3
- Combined endpoint of maternal adverse outcome, consisting of maternal death (death during pregnancy or within 42 days of delivery), eclampsia, pulmonary edema, severe renal impairment, cerebrovascular accident, placental abruption, and/or liver hematoma or rupture.
- Combined endpoint of fetal adverse outcome, consisting of intrauterine fetal death (IUFD, including intrapartum death), suboptimal fetal condition based on the heart rate pattern on the CTG (as judged by the treating clinician), and/or fetal growth restriction (FGR)
- Combined endpoint of neonatal adverse outcome, consisting of neonatal death (within 28 days of birth), intraventricular hemorrhage (grade III or IV), retinopathy of prematurity requiring treatment, necrotizing enterocolitis (grade II or higher), bronchopulmonary dysplasia, neonatal sepsis, and/or cystic periventricular leukomalacia (grade II or higher)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Metformine HCl 500 mg Teva, filmomhulde tabletten
PRD2381266 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 3000 mg milligram(s)
- Max total dose
- 294000 mg milligram(s)
- Max treatment duration
- 98 Day(s)
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- RVG 111960
- MA holder
- TEVA NEDERLAND B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Overencapsulation for blinding purposes
Placebo 1
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
Amsterdam UMC
- Sponsor organisation
- Amsterdam UMC
- Address
- De Boelelaan 1117
- City
- Amsterdam
- Postcode
- 1081 HV
- Country
- Netherlands
Scientific contact point
- Organisation
- Amsterdam UMC
- Contact name
- PI-NL Research Team
Public contact point
- Organisation
- Amsterdam UMC
- Contact name
- PI-NL Research Team
Locations
1 EU/EEA country · 8 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruiting | 180 | 8 |
| Rest of world | — | 0 | — |
Investigational sites
Academisch Ziekenhuis Maastricht
Verloskunde & Gynaecologie, P Debyelaan 25, 6229 HX, Maastricht
Universitair Medisch Centrum Utrecht
Verloskunde & Gynaecologie, Heidelberglaan 100, 3584 CX, Utrecht
Isala Klinieken Stichting
Verloskunde & Gynaecologie, Dokter Van Heesweg 2, 8025 AB, Zwolle
Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
Verloskunde & Gynaecologie, Dr. Molewaterplein 60, 3015 GJ, Rotterdam
Universitair Medisch Centrum Groningen
Verloskunde & Gynaecologie, Hanzeplein 1, 9713 GZ, Groningen
Maxima Medisch Centrum
Verloskunde & Gynaecologie, De Run 4600, 5504 DB, Veldhoven
Radboud universitair medisch centrum / RADBOUDUMC
Verloskunde & Gynaecologie, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen
Amsterdam UMC Stichting
Verloskunde & Gynaecologie, De Boelelaan 1117, 1081 HV, Amsterdam
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 |
|---|---|---|---|---|---|
| Netherlands | 2025-08-25 | 2025-09-19 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 8 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2023-510382-10-00 | 1.2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Leaflet | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Movie | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment material Text | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF | 3.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Metformin | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis NL 2023-510382-10-00 | 1 |
Application history
3 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-06-20 | Netherlands | Acceptable with conditions 2024-09-20
|
2024-09-24 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-05-08 | Netherlands | Acceptable 2025-08-06
|
2025-08-06 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-05-18 | Netherlands | Acceptable 2025-08-06
|
2026-05-18 |