Pre-Eclampsia Onset Less Than 37 WeeksPhase 3PI-NLNCT06452498
Preeclampsia Intervention Netherlands
A Phase 3 study testing Metformin Hydrochloride in people with Pre-Eclampsia Onset Less Than 37 Weeks and Pre-Eclampsia, run by Amsterdam UMC.
Trial summary
The goal of this study is to find out if pregnant individuals with preterm preeclampsia (PE) who are treated with metformin can stay pregnant for longer, and if this is safe(r) for the mother and child. Preterm PE affects about 1 in 100 pregnant individuals in the Netherlands. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Pre-Eclampsia Onset Less Than 37 Weeks, Pre-Eclampsia, Pre-Eclampsia; Complicating Pregnancy
- What is being tested?
- Metformin Hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- No sites listed yet
- Study dates
- Aug 2024to Jul 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- All of the following:
- Aged 18 years or older
- Singleton pregnancy
- Gestational age between 23+0 and 31+6 weeks
- A diagnosis of preterm preeclampsia, defined according to modified International Society for the Study of Hypertension in Pregnancy (ISSHP) classification, including only those who have proteinuria (≥300 mg of protein in a 24-hour urine specimen or a protein-creatinine-ratio >50 in a single urine sample)
- Estimated fetal weight >400 grams
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- 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.
- Ability to understand English or Dutch
- Ability and willingness to provide written informed consent
Who cannot join
- Any of the following:
- 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 the use of metformin (e.g., severe renal insufficiency, acute metabolic acidosis, severe liver insufficiency)
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Metformin for the Prolongation of Pregnancy in Preterm Preeclampsia
The goal of this study is to find out if pregnant individuals with preterm preeclampsia (PE) who are treated with metformin can stay pregnant for longer, and if this is safe(r) for the mother and child. Preterm PE affects about 1 in 100 pregnant individuals in the Netherlands. Signs of preterm PE can be high blood pressure and protein in the urine in the second half of pregnancy (but before 32-34 weeks of pregnancy). Other symptoms can develop, such as problems with blood clotting and how well the blood cells, liver, lungs, and brain work. The disease can lead to serious complications for both the mother and child. The only way to cure preterm PE is to make sure the child is born, and many times, children have to be delivered (very) early (before 37 weeks). Children born (very) early can suffer from infections, breathing difficulties, and problems in their development.
Metformin is a medicine used to treat high blood sugar during and outside of pregnancy. In a previous study in South Africa, women with preterm PE that used metformin were able to safely remain pregnant for an extra week. Similarly, the main goal of the Preeclampsia Intervention NetherLands (PI-NL) study is to see if patients with preterm PE in the Netherlands that use metformin can remain pregnant for a longer time than patients taking a placebo. A placebo is a look-a-like capsule that contains no active ingredients. Researchers, the treating medical team, and participants will not know which participant gets which treatment. In addition, all participants will receive the standard care that all preterm PE patients get.
Read the detailed description
Preterm preeclampsia (PE) is a severe hypertensive disorder of pregnancy and a major cause of maternal and perinatal morbidity and mortality. Currently, the only treatment to halt disease progression is delivery of the dysfunctional placenta and thereby the child. This often happens prematurely. Being able to safely (for mother and child) extend pregnancy, even by a few days, is expected to reduce the short- and long-term risks associated with (severe) prematurity. Preclinical and recent clinical evidence presents metformin, a drug commonly used to treat diabetes in and outside of pregnancy, as a promising treatment candidate for preterm PE. Metformin might reduce inflammation, oxidative stress, and anti-angiogenesis, and improve endothelial function. In a recent South African trial, use of metformin was associated with a safe median 7.6 day prolongation of pregnancy in women with preterm PE, compared to placebo. There was a nonsignificant increase in the neonatal birthweight and a decrease in the length of stay in any neonatal nursery. Metformin did not lead to any serious adverse events.
The goal of this multicenter, triple-blind, randomized placebo-controlled trial is to investigate whether metformin can safely prolong gestation in patients with preterm PE in the Dutch population. Secondary outcomes include composite adverse maternal, fetal, and neonatal outcomes. Cost-effectiveness of the treatment will be evaluated.
- Conditions
- Pre-Eclampsia Onset Less Than 37 Weeks, Pre-Eclampsia, Pre-Eclampsia; Complicating Pregnancy, Pre-Eclampsia as Antepartum Condition, Pre-eclampsia or Eclampsia With Pre-existing Hypertension, Pre-Eclampsia; Affecting Fetus
- Being tested
- Metformin Hydrochloride, Placebo
- Keywords
- Preterm Preeclampsia, Metformin, RCT, Placebo, Gestational Prolongation, Treatment, Pregnancy, Multicenter, Preterm, HELLP Syndrome, Hypertensive disorders of pregnancy, Preeclampsia, Randomized controlled trial
- Medical subject headings
- Pre-Eclampsia, Pregnancy Complications, HELLP Syndrome, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin HydrochlorideDrug
Also called Metformin, Metformin HCl
Metformin Hydrochloride encapsulated immediate-release tablet of 500 mg, backfilled with cellulose.
PlaceboDrug
Capsule filled with cellulose.
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Metformin 3000 mg divided by three daily doses (3 times 2 capsules of 500 mg; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care. Receives: Drug: Metformin Hydrochloride |
| Placebo | Placebo comparator | Placebo, divided by three daily doses (3 times 2 capsules; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of days between randomization and delivery
Prolongation of gestation
Measured: Time between randomization and delivery (up to 37 weeks of gestation)
Secondary outcomes (3)
Number of participants reaching a composite maternal adverse outcome
Combined endpoint of maternal death (during pregnancy or within 42 days postpartum), eclampsia, pulmonary edema, severe renal impairment, cerebrovascular accident, placental abruption, and/or liver hematoma or rupture.
Measured: Randomization till 90 days postpartum (unless otherwise specified)
Number of participants reaching a composite fetal adverse outcome
Combined endpoint of intrauterine fetal demise, suboptimal fetal condition based on CTG, and fetal growth restriction.
Measured: Randomization till delivery (up to 37 weeks of gestation)
Number of participants reaching a composite neonatal adverse outcome
Combined endpoint of neonatal death (within 28 days after birth), grade 3 or 4 intraventricular hemorrhage, retinopathy of prematurity requiring treatment, necrotizing enterocolitis (grade II or higher), bronchopulmonary dysplasia, neonatal sepsis, and cystic periventricular leukomalacia (grade II or higher)
Measured: Birth till 90 days after birth (unless otherwise specified)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2024
- Study startAug 2024 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pre-Eclampsia Onset Less Than 37 WeeksStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Two-arm trial with intervention arm (metformin) and comparator arm (placebo), aside from usual care for all patients.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 180 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC
- Sponsor type
- University, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Responsible party
- Principal investigator, Dr Rebecca C. Painter, Amsterdam UMC
- Investigators
- R.C. Painter, Prof, MD, PhD, Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06452498
- Sponsor's protocol ID
- PI-NL trial
- Other IDs
- 2023-510382-10-00, 2023
- Acronym
- PI-NL
- Status last verified
- Jun 2024
- First submitted
- 31 May 2024
- Last updated
- 11 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The investigators plan to collaborate with researchers doing similar Preeclampsia Intervention (PI) trials.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin for the Prolongation of Pregnancy in Preterm Preeclampsia
- ClinicalTrials.gov ID
- NCT06452498
- Acronym / sponsor ID
- PI-NL / PI-NL trial
- Conditions
- Pre-Eclampsia Onset Less Than 37 Weeks, Pre-Eclampsia, Pre-Eclampsia; Complicating Pregnancy, Pre-Eclampsia as Antepartum Condition, Pre-eclampsia or Eclampsia With Pre-existing Hypertension, Pre-Eclampsia; Affecting Fetus
- Keywords
- Preterm Preeclampsia, Metformin, RCT, Placebo, Gestational Prolongation, Treatment, Pregnancy, Multicenter
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 180 participants (estimated)
- Lead sponsor
- Amsterdam UMCUniversity, hospital or other
- Collaborators
- ZonMw: The Netherlands Organisation for Health Research and Development
- Study start
- Aug 2024 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 11 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to find out if pregnant individuals with preterm preeclampsia (PE) who are treated with metformin can stay pregnant for longer, and if this is safe(r) for the mother and child. Preterm PE affects about 1 in 100 pregnant individuals in the Netherlands. Signs of preterm PE can be high blood pressure and protein in the urine in the second half of pregnancy (but before 32-34 weeks of pregnancy). Other symptoms can develop, such as problems with blood clotting and how well the blood cells, liver, lungs, and brain work. The disease can lead to serious complications for both the mother and child. The only way to cure preterm PE is to make sure the child is born, and many times, children have to be delivered (very) early (before 37 weeks). Children born (very) early can suffer from infections, breathing difficulties, and problems in their development.
Metformin is a medicine used to treat high blood sugar during and outside of pregnancy. In a previous study in South Africa, women with preterm PE that used metformin were able to safely remain pregnant for an extra week. Similarly, the main goal of the Preeclampsia Intervention NetherLands (PI-NL) study is to see if patients with preterm PE in the Netherlands that use metformin can remain pregnant for a longer time than patients taking a placebo. A placebo is a look-a-like capsule that contains no active ingredients. Researchers, the treating medical team, and participants will not know which participant gets which treatment. In addition, all participants will receive the standard care that all preterm PE patients get.
Detailed description
Preterm preeclampsia (PE) is a severe hypertensive disorder of pregnancy and a major cause of maternal and perinatal morbidity and mortality. Currently, the only treatment to halt disease progression is delivery of the dysfunctional placenta and thereby the child. This often happens prematurely. Being able to safely (for mother and child) extend pregnancy, even by a few days, is expected to reduce the short- and long-term risks associated with (severe) prematurity. Preclinical and recent clinical evidence presents metformin, a drug commonly used to treat diabetes in and outside of pregnancy, as a promising treatment candidate for preterm PE. Metformin might reduce inflammation, oxidative stress, and anti-angiogenesis, and improve endothelial function. In a recent South African trial, use of metformin was associated with a safe median 7.6 day prolongation of pregnancy in women with preterm PE, compared to placebo. There was a nonsignificant increase in the neonatal birthweight and a decrease in the length of stay in any neonatal nursery. Metformin did not lead to any serious adverse events.
The goal of this multicenter, triple-blind, randomized placebo-controlled trial is to investigate whether metformin can safely prolong gestation in patients with preterm PE in the Dutch population. Secondary outcomes include composite adverse maternal, fetal, and neonatal outcomes. Cost-effectiveness of the treatment will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two-arm trial with intervention arm (metformin) and comparator arm (placebo), aside from usual care for all patients.
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: Metformin HydrochlorideMetformin 3000 mg divided by three daily doses (3 times 2 capsules of 500 mg; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, divided by three daily doses (3 times 2 capsules; following a step-up schedule) from randomization till delivery, aside from usual preterm preeclampsia care. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Aged 18 years or older
- Singleton pregnancy
- Gestational age between 23+0 and 31+6 weeks
- A diagnosis of preterm preeclampsia, defined according to modified International Society for the Study of Hypertension in Pregnancy (ISSHP) classification, including only those who have proteinuria (≥300 mg of protein in a 24-hour urine specimen or a protein-creatinine-ratio >50 in a single urine sample)
- Estimated fetal weight >400 grams
Key exclusion criteria (7 listed)
- 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 the use of metformin (e.g., severe renal insufficiency, acute metabolic acidosis, severe liver insufficiency)
- Use of drugs that might interact with metformin
- Suspicion of a major fetal anomaly and/or chromosomal abnormality
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin HydrochlorideAlso: Metformin, Metformin HClMetformin Hydrochloride encapsulated immediate-release tablet of 500 mg, backfilled with cellulose. | Drug | Metformin |
| PlaceboCapsule filled with cellulose. | Drug | Placebo |
Primary outcome
Number of days between randomization and delivery
Time frame: Time between randomization and delivery (up to 37 weeks of gestation)
Prolongation of gestation
3 secondary outcomes
Number of participants reaching a composite maternal adverse outcome
Time frame: Randomization till 90 days postpartum (unless otherwise specified)
Number of participants reaching a composite fetal adverse outcome
Time frame: Randomization till delivery (up to 37 weeks of gestation)
Number of participants reaching a composite neonatal adverse outcome
Time frame: Birth till 90 days after birth (unless otherwise specified)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Individual participant dataSharing planned: Yes. The investigators plan to collaborate with researchers doing similar Preeclampsia Intervention (PI) trials.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
R.C. Painter, Prof, MD, PhD principal investigator
Amsterdam UMC
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Metformin Hydrochloride in people with Pre-Eclampsia Onset Less Than 37 Weeks and Pre-Eclampsia, run by Amsterdam UMC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact M. Khelil, MD (+31 20 566 9111, PI_NL@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of days between randomization and delivery (time frame: Time between randomization and delivery (up to 37 weeks of gestation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024.