Proof-of-Concept Trial on Selective Removal of SFlt-1 in Pregnant Women with Preeclampsia Via Apheresis
Not Applicable
Active, not recruiting
- Conditions
- Preeclampsia
- Interventions
- Device: TheraSorb sFlt-1 adsorber
- Registration Number
- NCT02923206
- Lead Sponsor
- Miltenyi Biomedicine GmbH
- Brief Summary
This clinical investigation is a medical device trial to examine the safety and efficacy of TheraSorb sFlt-1 adsorber treatment of pregnant patients with preeclampsia.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 21
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase 0 - healthy volunteers TheraSorb sFlt-1 adsorber Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure. Phase A - preeclampsia patients TheraSorb sFlt-1 adsorber 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 - preeclampsia patients TheraSorb sFlt-1 adsorber 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.
- Primary Outcome Measures
Name Time Method Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0) until 2 weeks post treatment Occurrence of AEs and SAEs in pregnant subjects and the fetus or infant until the 6 weeks post-delivery visit is reached (Phase A-B). until 6 weeks post delivery
- Secondary Outcome Measures
Name Time Method Phase 0: Concentration of antibody leaching during an apheresis procedure During an apheresis procedure (1 day) Phase 0: Change of HAMA levels in pre- and post apheresis blood until 2 weeks post treatment Phase 0: Evaluate blood pressure values until 2 weeks post treatment Phase 0: Complement activation levels pre-, during and post apheresis. Before, during and directly following the performance of the single apheresis treatment (1 day) Phase 0: Determine changes of sFlt-1 levels. until 2 weeks post treatment Phase 0: Evaluate spot urine values until 2 weeks post treatment Phase A/B: Occurrence of SAEs in the one year follow-up period until end of FU, (1 year) Phases A/B: Time and method of delivery, and anesthesia administered at birth Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization. Following birth up to one year Phases A/B: Evaluate antibody leaching in phase A. During the performance of the single apheresis treatment in Phase A (1 day) as well as pre and 3hrs post apheresis Phases A and B: Evaluate maternal sFlt-1 levels. Constant measures throughout the trial until delivery (up to 19 weeks) Phases A/B: Evaluate the sFlt-1/PlGF ratio. Constant measures throughout the trial until delivery (up to 19 weeks) Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth. at birth Phases A/B: Evaluate standard markers of fetal development throughout pregnancy. From start of trial until delivery (up to 19 weeks) Phases A/B: Evaluate standard markers of neonatal development. Directly following delivery until end of FU (1 year) Phases A/B: Determine HAMA levels until 6 week FU visit
Trial Locations
- Locations (4)
Universitätsklinikum Köln
🇩🇪Cologne, Germany
Universitätsklinikum Leipzig
🇩🇪Leipzig, Germany
Cambridge Clinical Trials Unit, Addenbrooke's Hospital
🇬🇧Cambridge, United Kingdom
Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
🇬🇧Oxford, United Kingdom