Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis (SAVE)
Preeclampsia
About this trial
This is an interventional treatment trial for Preeclampsia focused on measuring apheresis, pregnancy, pre-eclampsia, PE, sFlt-1, Pre-term
Eligibility Criteria
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.
Sites / Locations
- Universitätsklinikum KölnRecruiting
- Universitätsklinikum LeipzigRecruiting
- Cambridge Clinical Trials Unit, Addenbrooke's Hospital
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Experimental
Experimental
Phase 0 - healthy volunteers
Phase A - preeclampsia patients
Phase B - preeclampsia patients
Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
Phase A is a safety and dose-finding phase during which pregnant women diagnosed with preeclampsia will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
Phase B is a safety and efficacy phase during which pregnant women diagnosed with preeclampsia will undergo TheraSorb sFlt-1 adsorber apheresis procedures up to twice weekly.