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

December 21, 2015 updated by: Assistance Publique - Hôpitaux de Paris

Usefulness of Extracorporeal Removal of sFlt-1 in Women With Severe Preeclampsia at Less Than 26 Weeks' Gestation

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed 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

Study Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Créteil, France
        • CHIC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Apheresis arm
Apheresis for extracorporal removal of sFlt-1
Device: Apheresis for extracorporal removal of sFlt-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Baby discharged alive or alive at 6 months if hospitalized
Time Frame: 6 months
During the first step (inclusion of 8 patients) analysis is done continuously, and if 3 women have unsuccess primary endpoint, first step and the study are stopped, with a conclusion of failure of the procedure of lipapheresis.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pregnancy prolongation and preeclampsia related adverse outcomes
Time Frame: 15 weeks
The data will be measured during the participation of the patient : 15 weeks = 11 weeks of pregnancy monitoring (from 23 to 34 weeks' gestation) + 4 weeks postpartum
15 weeks
Immunoadsorption tolerance for the mother during the session of lipapheresis
Time Frame: 11 weeks
A description of the following variables will be used: blood pressure during the session, infectious or hemorrhagic events subsequent infusion and / or technique. The time frame is 11 weeks as a maximum : 11 weeks of pregnancy monitoring (from 23 to 34 weeks' gestation)
11 weeks
Foetal immunoadsorption tolerance during the session of lipapheresis
Time Frame: 11 weeks
Measuring of the heart monitoring's data will be used. The time frame is 11 weeks as a maximum : 11 weeks of pregnancy monitoring (from 23 to 34 weeks' gestation)
11 weeks
Circulating levels of sFlt1, the placental growth factor (PlGF) and soluble endoglin (sEng) until deliverance
Time Frame: 12 weeks
For the measure of the maternal adsorptive efficiency, the following parameters will be described: circulating levels of sFlt1, the placental growth factor (PlGF) and soluble endoglin (sEng). The time frame is 12 weeks : 11 weeks of pregnancy monitoring (from 23 to 34 weeks' gestation) + until deliverance
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Bassam HADDAD, CHIC Créteil

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

November 3, 2014

First Submitted That Met QC Criteria

November 6, 2014

First Posted (Estimate)

November 7, 2014

Study Record Updates

Last Update Posted (Estimate)

December 22, 2015

Last Update Submitted That Met QC Criteria

December 21, 2015

Last Verified

June 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P130928/ N°IDRCB2014-A01044-43

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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