Preeclampsia Intervention Netherlands

NCT06452498 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: PI-NL trial2023-510382-10-00
• Study Type: interventional
• Target: 180
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

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; HELLP Syndrome Complicating Pregnancy; HELLP Syndrome; HELLP

Keywords

Preterm Preeclampsia; Metformin; RCT; Placebo; Gestational Prolongation; Treatment; Pregnancy; Multicenter; Preterm; HELLP Syndrome; Hypertensive disorders of pregnancy; Preeclampsia; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Number of days between randomization and delivery

  Prolongation of gestation

  Time between randomization and delivery (up to 37 weeks of gestation)

Secondary Outcomes (3)

• Number of participants reaching a composite maternal adverse outcome

  Randomization till 90 days postpartum (unless otherwise specified)

• Number of participants reaching a composite fetal adverse outcome

  Randomization till delivery (up to 37 weeks of gestation)

• Number of participants reaching a composite neonatal adverse outcome

  Birth till 90 days after birth (unless otherwise specified)

Other Outcomes (11)

• Maternal individual exploratory outcomes

  Randomization till 90 days postpartum (unless otherwise specified)

• Fetal individual exploratory outcomes

  Randomization till 90 days postpartum (unless otherwise specified)

• Neonatal individual exploratory outcomes

  Randomization till 90 days postpartum (unless otherwise specified)

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Metformin Hydrochloride DRUG

Metformin Hydrochloride encapsulated immediate-release tablet of 500 mg, backfilled with cellulose.

Also known as: Metformin, Metformin HCl

Metformin

Placebo DRUG

Capsule filled with cellulose.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC: lead
• ZonMw: The Netherlands Organisation for Health Research and Development: collaborator

MeSH Terms

Conditions

Pre-Eclampsia; Pregnancy Complications; HELLP Syndrome; Premature Birth

Interventions

Metformin

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• R.C. Painter, Prof, MD, PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M. Khelil, MD

CONTACT

+31 20 566 9111; PI_NL@amsterdamumc.nl

R.C. Painter, Prof, MD, PhD

CONTACT

+31 20 566 9111; PI_NL@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subjects, treating clinicians, and trial investigators will be blinded to the allocated treatment. Masking will be removed once the database has been locked, after which data analysis will be undertaken.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: Two-arm trial with intervention arm (metformin) and comparator arm (placebo), aside from usual care for all patients.

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 11, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: June 11, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE