Clinical trial NCT02923206: Proof-of-Concept Trial on Selective Removal of SFlt-1 in Pregnant Women with Preeclampsia Via Apheresis
Official title: Proof-of-Concept Trial on Selective Removal of the Antiangiogenic Factor Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) in Pregnant Women with Preeclampsia Via Apheresis Utilizing the Flt-1 Adsorption Column
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Preeclampsia
Keywords: apheresis
pregnancy
pre-eclampsia
PE
sFlt-1
Pre-term
Lead sponsor: Miltenyi Biomedicine GmbH
Sponsor class: INDUSTRY
Collaborators: name: Cromsource
First posted: 2016-10-04
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0)
timeFrame: until 2 weeks post treatment
measure: 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).
timeFrame: until 6 weeks post delivery
Secondary outcomes:
measure: Phase 0: Determine changes of sFlt-1 levels.
timeFrame: until 2 weeks post treatment
measure: Phase 0: Complement activation levels pre-, during and post apheresis.
timeFrame: Before, during and directly following the performance of the single apheresis treatment (1 day)
measure: Phase 0: Concentration of antibody leaching during an apheresis procedure
timeFrame: During an apheresis procedure (1 day)
measure: Phase 0: Change of HAMA levels in pre- and post apheresis blood
timeFrame: until 2 weeks post treatment
measure: Phase 0: Evaluate blood pressure values
timeFrame: until 2 weeks post treatment
measure: Phase 0: Evaluate spot urine values
timeFrame: until 2 weeks post treatment
measure: Phase A/B: Occurrence of SAEs in the one year follow-up period
timeFrame: until end of FU, (1 year)
measure: Phases A/B: Evaluate antibody leaching in phase A.
timeFrame: During the performance of the single apheresis treatment in Phase A (1 day) as well as pre and 3hrs post apheresis
measure: Phases A and B: Evaluate maternal sFlt-1 levels.
timeFrame: Constant measures throughout the trial until delivery (up to 19 weeks)
measure: Phases A/B: Evaluate the sFlt-1/PlGF ratio.
timeFrame: Constant measures throughout the trial until delivery (up to 19 weeks)
measure: Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth.
timeFrame: at birth
measure: Phases A/B: Determine HAMA levels
timeFrame: until 6 week FU visit
measure: Phases A/B: Time and method of delivery, and anesthesia administered
timeFrame: at birth
measure: Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization.
timeFrame: Following birth up to one year
measure: Phases A/B: Evaluate standard markers of fetal development throughout pregnancy.
timeFrame: From start of trial until delivery (up to 19 weeks)
measure: Phases A/B: Evaluate standard markers of neonatal development.
timeFrame: Directly following delivery until end of FU (1 year)
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Universitätsklinikum Köln
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Cambridge
country: United Kingdom
facility: Cambridge Clinical Trials Unit, Addenbrooke's Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
Study officials:
affiliation: University Clinic Cologne
name: Thomas Benzing, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: