Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis

Reduced criteria! Phase 0 Inclusion Criteria: * Age ≥18 and ≤45 years; * Male or female; * Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and practice two reliable methods of contraception throughout the study. Exclusion Criteria: * Dysfunction of cerebral nervous system and/or heart disease; * History of preexisting chronic renal disease; * Treatment with ACE inhibitors; * Therapeutic full anticoagulation therapy prior to trial entry; * Liver abnormalities; * Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia; * Active hepatitis B, C, or tuberculosis infection or HIV infection * Hypersensitivity to heparin and/or citrate; * Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions; * Known intolerance to extracorporeal procedures in general or towards one of the individual excipients or towards other supporting agents; * Drug or alcohol abuse within the last 2 years; * Lack of compliance of subject; * History or diagnosis of severe periodontitis; Phase A and B Inclusion Criteria: * Age \>18 and ≤45 years ; * Pregnant woman with pre-term preeclampsia * sFlt-1/PlGF ratio ≥85 ; * sFlt-1 level of ≥ 8000pg/mL Exclusion Criteria: Maternal exclusion criteria * History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valve disease; * History of preexisting chronic renal disease (CKD stage \>3a, eGFR ≤45ml/min/1.73m²); * Treatment with ACE inhibitors; * Therapeutic full anticoagulation therapy prior to trial entry; * Signs or history of clinically significant cerebral nervous system dysfunction; * History of clinically significant liver abnormalities; * Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia; * Active hepatitis B, C, tuberculosis infection or HIV-positive status; * Any condition that the investigator deems a risk to the patient or fetus in completing the trial; * Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions; * Drug or alcohol abuse within the last 2 years; * Lack of compliance of patient; * Known intolerance to extracorporeal procedures in general or to one of the excipients or other supporting agents; * Hypersensitivity to heparin and/or citrate; * \< 30 0/7 weeks of gestation and abnormal CTG and/or abnormal Ductus venosus Doppler flow, * ≥30 0/7 weeks of gestation and Doppler evidence of umbilical artery Absent or Reversed End-Diastolic Velocity (AREDV); * Various Placental exclusion criteria; * Multiple pregnancy * History or diagnosis of severe periodontitis Fetal exclusion criteria * Any known trisomy; * Amniotic fluid index \<5cm (greatest single pocket \<2cm); * Estimated fetal weight \<3rd percentile for gestational age; * Fetus which are at high risk of heart disease; * Fetus with congenital heart defect; * Fetal signs of bleeding; * Hydrops fetalis; * Pathological fetal Doppler flow of the ductus venosus (absent A-wave in two measurements); * Evidence of severe fetal malformations; * Known infection of fetus; * Known severe anemia.