A Feasibility Study to Evaluate the Safety of the KNP-1000 Apheresis System in Severe Preeclampsia

Official title

A Feasibility Study to Evaluate the Safety of the KNP-1000 Apheresis System in Patients With Preeclampsia With Severe Features

Overview

The study will primarily evaluate safety of the KNP-1000 apheresis system for pregnant women and their fetuses diagnosed with preeclampsia with severe features between 23- and 32-weeks' gestation (very preterm).

Interventions

• Device KNP-1000 Apheresis System
  sFlt-1 is removed from the participants' plasma through treatment.

Primary outcome measures

• Antepartum maternal and fetal device-related serious adverse events [Time frame: Until date of delivery]
• Postpartum maternal and neonatal device-related serious adverse events [Time frame: Following delivery until end of follow-up (2 years)]
• Maternal, fetal, and neonatal mortality [Time frame: Until end of follow-up (2 years)]
• Obstetric complication [Time frame: Until discharge or 6 weeks after delivery, whichever occurs first]
• Fetal complications [Time frame: Until date of delivery]
• Neonatal morbidities associated with premature delivery [Time frame: Following delivery until discharge or 6 weeks after delivery, whichever occurs first]
• Neonatal intensive care unit (NICU) admissions [Time frame: From date of NICU admission until the date of NICU discharge, assessed up to 24 months]

Secondary outcome measures (12)

• Prolongation of pregnancy [Time frame: Until date of delivery]
• Maternal systolic blood pressure [Time frame: Until discharge or 6 weeks after delivery, whichever occurs first]
• Maternal diastolic blood pressure [Time frame: Until discharge or 6 weeks after delivery, whichever occurs first]
• Maternal proteinuria [Time frame: Until discharge or 6 weeks after delivery, whichever occurs first, an average of 4 months]
• Gestational age of the neonate at delivery [Time frame: At date of delivery]
• Weight of neonate at delivery [Time frame: At date of delivery]
• Amniotic fluid volume [Time frame: Until the date of delivery, an average of 3 months]
• Fetal umbilical artery flow [Time frame: Until the date of delivery, an average of 3 months]
• Uterine artery flow [Time frame: Until the date of delivery, an average of 3 months]
• Maternal low-density lipoprotein cholesterol (LDL-C) levels [Time frame: Until discharge or 6 weeks after delivery, whichever occurs first, an average of 4 months]
• Fetal growth restriction [Time frame: Until date of delivery]
• APGAR scores [Time frame: At date of delivery]

Eligibility criteria

Inclusion criteria

A participant is deemed suitable for inclusion in the investigation if she meets the following criteria:

• Pregnant woman ≥ 23 0/7 and \< 32 0/7 weeks gestation, aged 18 to 45 years, hospitalized for preeclampsia at time of enrollment.
• Severe hypertension ever defined by resting systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 110 mm Hg on two occasions measured at least 4 hours apart.
• Proteinuria, defined as ≥ 300 mg protein in a 24-hour urine collection or ≥ 0.3 protein/creatinine ratio.
• Provision of signed and dated informed consent form.

Exclusion criteria

A participant will be excluded from the investigation if any of the following maternal or fetal criteria are met.

Maternal Exclusion Criteria:

• Documented history of chronic hypertension, defined as systolic BP ≥ 140mmHg and/or systolic BP ≥ 90 mmHg before pregnancy or prior to 20 weeks of gestation.
• Documented history of proteinuria prior to pregnancy or prior to 20 weeks of gestation.
• Taking any form of angiotensin cascade blocker or angiotensin-converting enzyme (ACE) inhibitor at time of enrollment.
• Documented history of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure, or valvular disease.
• Actively receiving therapeutic anticoagulation therapy or within the therapeutic window after ceasing anticoagulation therapy at the time of enrollment.
• Any condition which, in the opinion of the Investigator, would necessitate immediate delivery within 24 hours.
• Signs or history of cerebral nervous system dysfunction, including seizures, cerebral edema (previously confirmed by computed tomography scan or magnetic resonance imaging per medical records).
• Confirmed or suspected diagnosis of pulmonary edema at time of enrollment.
• Diagnosis of HELLP syndrome.
• Thrombocytopenia (platelet count \< 100,000/mm3) at time of enrollment.
• Anemia defined as hemoglobin \< 8 g/dL at time of enrollment.
• Absent or reverse flow on umbilical Doppler ultrasound exam at the time of screening, or documented history of negative or reverse flow during the current gestation period.
• Diagnosis of placenta previa during the current gestation period.
• Preterm labor at or before time of screening.
• Documented medical history of active hepatitis B virus, hepatitis C virus (HCV), syphilis, tuberculosis infection, or human immunodeficiency virus (HIV) positive status.
• Any condition that the Investigator deems a risk to the study participant or fetus in completing the investigation.
• Hypersensitivity to dextran sulfate cellulose or heparin.
• Multiple gestation.
• Documented history of familial hypercholesterolemia.
• Suspicion or diagnosis of placental abruption during the current gestation.
• Patients who have received the drug treatment not recommended by the American College of Obstetricians and Gynecologists (ACOG) practice bulletin Gestational Hypertension and Preeclampsia (the clinical management guidelines) within 6 months prior to enrollment.
• Patients who have participated in another clinical trial within 6 months prior to enrollment.

Fetal Exclusion Criteria:

• Documented record of chromosomal anomalies.
• Identifiable structural fetal abnormalities present at time of screening or a record of such abnormalities prior to enrollment.
• Oligohydramnios, defined as Amniotic fluid index (AFI) less than 5 cm when measured using the four-quadrant method at time of enrollment.
• Fetal growth restriction (FGR) defined as estimated fetal weight (EFW) below the 5th percentile for gestational age.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06580405 · KNP-1000-US01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗