Clinical trial NCT05647096: Safety, Tolerability and Performance of the NucleoCapture Device in the Reduction of Circulating CfDNA/NETs in Subjects with Sepsis
Official title: Safety, Tolerability and Performance of the NucleoCapture Extracorporeal Therapeutic Apheresis Device in the Reduction of Circulating CfDNA/NETs in Subjects with Sepsis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Sepsis
Respiratory Failure
Keywords: Sepsis
Respiratory failure
Lead sponsor: Santersus AG
Sponsor class: INDUSTRY
Collaborators: name: ISS AG
First posted: 2022-12-12
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomly assigned to either the interventional treatment arm (SOC plus NucleoCapture) or the SOC treatment arm in a 2:1
Primary purpose: TREATMENT

Brief summary: This is a prospective, multinational, multicentre, randomised, parallel-group, open-label study to assess the safety, tolerability and performance of the NucleoCapture extracorporeal apheresis device in the reduction of circulating cell-free DNA (cfDNA)/Neutrophil Extracellular Traps (NETs) in sepsis patients.

Detailed description: This study investigates the safety, tolerability and performance of the NucleoCapture extracorporeal apheresis device in patients with sepsis and respiratory failure. Sepsis is a common condition in hospital settings and is associated with high rates of morbidity and mortality and despite ongoing development in the treatment and supportive care of sepsis, mortality remains considerable.

cfDNA/NET therapeutic apheresis with NucleoCapture is indicated for the treatment of sepsis and for the treatment/prevention of septic shock. Participants will be randomised to receive either standard of care (SOC) or SOC plus NucleoCapture treatment, SOC will be according to the current guidelines described by the Surviving Sepsis Campaign: international guidelines for the management of sepsis and septic shock. Participants in the SOC plus NucleoCapture arm will receive one treatment session with NucleoCapture per day, for the first three days. Each treatment session with NucleoCapture will last for up 6 hours, aiming to treat 4.5 plasma volumes. Treatment sessions with NucleoCapture treating less than 3.5 plasma volumes will be counted as incomplete and the treatment session will be repeated on the following day, up to day 5 maximum.

Assessments and tests will take place for all participants whilst in Intensive Care Unit (ICU) on days 1 to 5, day 7, day 14, day 21 and day 28. Participants transferred to ward-based care before day 28 will receive no further study assessment visits from the point of transfer to ward-based care, apart from day 28 in which participants will receive a final study assessment visit.

Eligibility criteria: Inclusion Criteria:

* Adult patients aged 18-75
* Proven or suspected respiratory sepsis aetiology
* Acute respiratory failure currently requiring invasive mechanical ventilation for not more than 48 hours duration
* Horowitz Index for Lung Function (Pa02/Fi02 Ratio) ≤200mmHg or ≤26.6kPa
* Sequential organ failure assessment score (SOFA) ≥4 and ≤ 14
* Have provided written informed consent or consent is given by the patient's legally designated representative or an independent physician (if possible, according to local law).

Exclusion Criteria:

* Expected duration of invasive mechanical ventilation less than 48 hours
* The use of other non-routine extracorporeal sepsis treatments such as very high flux renal replacement therapy (\>60ml/kg/h total exchange), use of high cut off filters or other non-routine extracorporeal treatment columns such as Cytosorb, Toramyxcin, etc).
* Presence of severe multiple organ failure at the point of enrolment as evidenced by:

  * Severe refractory vasoplegic failure

    * Norepinephrine dose \> 0.60 μg/kg/min
    * Use of epinephrine
  * Concomitant cardiogenic shock, clinically suspected or CI\<2.2 if measured

    * Use of dobutamine, epinephrine, phosphodiesterase inhibitors or levosimendan
  * Coagulopathy as defined by platelet count \<50
* Calculated Plasma Volume greater than 5000ml as determined by an estimation of total blood volume (according to Nadler's formula, incorporating height, weight and sex) multiplied by (1- Haematocrit). A total blood volume calculator is available at https://www.omnicalculator.com/health/blood-volume
* Long term oxygen therapy or home oxygen use
* Liver cirrhosis (histologically proven or clinically suspected)
* Active bleeding
* Citrate intolerance if citrate is required for therapeutic apheresis
* Heparin allergy if heparin is required for therapeutic apheresis
* Metastatic disease with life expectancy of \<12 months and ECOG score of at least 2
* Haematological malignancy if not in remission
* Solid organ transplant and concomitant use of immunosuppression
* Dialysis dependent Chronic Kidney Disease (CKD Stage 5-D)
* Prior use of cardiopulmonary resuscitation (CPR) in index admission
* Requirement for extracorporeal membrane oxygenation (ECMO)
* Patient expected to die within 48 hours of admission to ICU
* Known allergy to components of NucleoCapture
* Current Participation in another interventional clinical trial
* Pregnancy (as established by the presence of beta human chorionic gonadotropin in urine or blood)

Primary outcomes:
measure: To demonstrate the NucleoCapture column reduces the amount of cfDNA/NETs in the plasma of participants with sepsis and respiratory failure
timeFrame: Within 6 hours from the baseline (pre-column) plasma
Secondary outcomes:
measure: Mean reduction in circulating cfDNA/NETs measured by circulating blood levels of nucleosomes (H.3.1)
timeFrame: Before and after treatment with the NucleoCapture column and at the start and end of a 6 hour period in the SOC treatment arm
measure: The clinical benefit of the NucleoCapture column in participants with sepsis and respiratory failure
timeFrame: From date of randomisation to day 21 for organ support and day 28 for survival
Other outcomes:
measure: The biological efficacy and performance of NucleoCapture will be assessed using routine biomarkers
timeFrame: At baseline, days 1 to 5, day 7 and day 14
measure: The biological efficacy and performance of NucleoCapture will be assessed using non-routine biomarkers
timeFrame: At baseline, days 1 to 5, day 7 and day 14
measure: Device handling and usability
timeFrame: Day 1 up to day 5
Locations:
city: Bonn
country: Germany
facility: University of Bonn
city: Dresden
country: Germany
facility: Technical University Dresden
city: Hannöver
country: Germany
facility: Hannover Medical School
city: Zürich
country: Switzerland
facility: University of Zurich
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: University College London
Study officials:
affiliation: Santersus AG
name: Andrew Aswani
role: PRINCIPAL_INVESTIGATOR
References: