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Usefulness of Extracorporeal Removal of sFLT-1 in Women With Very Early Severe Preeclampsia (ADENA)

A

Assistance Publique - Hôpitaux de Paris

Status and phase

Terminated
Phase 2

Conditions

Preeclampsia

Treatments

Device: Apheresis for extracorporal removal of sFlt-1

Study type

Interventional

Funder types

Other

Identifiers

NCT02286284
P130928/ N°IDRCB2014-A01044-43

Details and patient eligibility

About

Introduction Preeclampsia is a multifactorial disease that is responsible of important adverse maternal and perinatal outcomes. Recently, it has been suggested that soluble fms-like tyrosine kinase 1, s-Flt1, induces preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia.

The aim of our study is to see whether removal of s-Flt1 may improve perinatal death in women with very early severe preeclampsia at less than 26 weeks' gestation Patients and methods Phase II trial. Women with singleton pregnancy having severe preeclampsia at 23-256/7 weeks' gestation. Women under 18 years, with multiples, or severe fetal growth restriction (less than 5th centile), or abnormal fetal heart rate, or maternal complications (abruption, eclampsia, HELLP syndrome, pulmonary edema, DIC, liver hematoma) are excluded from the study. After blood pressure and maternal stabilization, women are approached for information and if they agree, to sign the trial consent.

Women have twice weekly extracorporeal removal of s-Flt1 until 34 weeks' gestation.

Primary endpoint or success of the procedure: baby alive or alive at 6 months if hospitalized Statistical procedure Simon minimax plan; P0: 60%, P1, 90%, alpha error: 5%, beta power; 90%. First step: number 8 patients. If success equal or less than 5, the study is stopped.

Second step: if success of 6 or more, the study is continued for 9 more patients.

Overall, a maximum of 17 patients will be included. The final success of extracorporeal removal of s-Flt1 will be considered if 14 or more babies will be alive or alive at 6 months if hospitalized.

Full description

Introduction Preeclampsia is a multifactorial disease that is responsible of important adverse maternal and perinatal outcomes. Recently, it has been suggested that soluble fms-like tyrosine kinase 1, s-Flt1, induces preeclampsia-like phenotype in experimental models and circulates at elevated levels in human preeclampsia.

The aim of our study is to see whether removal of s-Flt1 may improve perinatal death in women with very early severe preeclampsia at less than 26 weeks' gestation Patients and methods Phase II trial. Women with singleton pregnancy having severe preeclampsia at 23-256/7 weeks' gestation. Women under 18 years, with multiples, or severe fetal growth restriction (less than 5th centile), or abnormal fetal heart rate, or maternal complications (abruption, eclampsia, HELLP syndrome, pulmonary edema, DIC, liver hematoma) are excluded from the study. After blood pressure and maternal stabilization, women are approached for information and if they agree, to sign the trial consent.

They will then be admitted to the department of Renal intensive care of Tenon Hospital. LDL apheresis will be performed twice weekly, during 90 minutes per session, using the DALI 750 Kit and the ART device (Fresenius). sFlt1 will be measured in peripheral blood before and after each session. The treatment will end when delivery is indicated (whether because of threatening complications or because a viable term of pregnancy is achieved).

Primary endpoint or success of the procedure: a live born baby alive at 6 month after birth.

Secondary endpoints: days of pregnancy prolongation, blood pressure during apheresis, fetal heart rate monitoring after apheresis, maternal levels of s-Flt1, PlGF, and s-endoglin.

Maternal adverse outcomes: eclampsia, HELLP syndrome, DIC, pulmonary edema, abruption placentae, renal failure.

Neonatal outcome: gestational age at delivery, birth weight, Apgar score, patent ductus arteriosus, RDS, PVL, IVH, NEC, days in NICU.

Statistical procedure Simon minimax plan; P0: 60%, P1, 90%, alpha error: 5%, beta power; 90%. First step: number 8 patients. If success equal or less than 5, the study is stopped.

Second step: if success of 6 or more, the study is continued for 9 more patients.

Overall, a maximum of 17 patients will be included. The final success of extracorporeal removal of s-Flt1 will be considered if 14 or more babies will be alive at 6 months after birth

Enrollment

2 patients

Sex

Female

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Severe preeclampsia at less than 26 weeks' gestation
  • Singleton pregnancy
  • Signed consent

Exclusion criteria

  • Multiple pregnancy
  • Gestational age at 26 or above weeks' gestation
  • Estimated foetal weight at diagnosis <5th percentile
  • Abnormal fetal heart rate at entry, where feasible (>24 weeks' gestation)
  • Maternal complications at diagnosis: Uncontrolled blood pressure, HELLP syndrome, abruption, eclampsia pulmonary edema, renal failure, liver hematoma

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

2 participants in 1 patient group

Apheresis arm
Experimental group
Description:
Apheresis for extracorporal removal of sFlt-1
Treatment:
Device: Apheresis for extracorporal removal of sFlt-1

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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