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Safety, Tolerability and Performance of the NucleoCapture Device in the Reduction of Circulating cfDNA/NETs in Subjects With Sepsis (NUC-CAP)

Primary Purpose

Sepsis, Respiratory Failure

Status
Not yet recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
NucleoCapture device
Sponsored by
Santersus AG
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis focused on measuring Sepsis, Respiratory failure

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of Bonn
  • Technical University Dresden
  • Hannover Medical School
  • University of Zurich
  • Queen Elizabeth Hospital Birmingham
  • Royal Infirmary of Edinburgh
  • Liverpool University Hospital
  • Guy's and St Thomas' Hospital
  • University College London

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

NucleoCapture Treatment

Standard of Care

Arm Description

Participants in the NucleoCapture treatment arm will receive Standard of Care plus three treatment sessions with the NucleoCapture treatment device. The device consists of 100ml NucleoCapture selective adsorber.

Participants in the Standard of Care arm will receive standard medical care alone.

Outcomes

Primary Outcome Measures

To demonstrate the NucleoCapture column reduces the amount of cfDNA/NETs in the plasma of participants with sepsis and respiratory failure
The mean reduction of an expected ≥50% of the net amount of cfDNA/NETs across the NucleoCapture column at the end of each NuceoCapture treatment session

Secondary Outcome Measures

Mean reduction in circulating cfDNA/NETs measured by circulating blood levels of nucleosomes (H.3.1)
Mean relative reduction of circulating blood cfDNA/NETs at the end of a complete treatment session with NucleoCapture compared to the change in the mean levels of cfDNA/NETs over a 6 hour period in the SOC treatment arm
The clinical benefit of the NucleoCapture column in participants with sepsis and respiratory failure
Change in organ support and survival

Full Information

First Posted
December 3, 2022
Last Updated
April 11, 2023
Sponsor
Santersus AG
Collaborators
ISS AG
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1. Study Identification

Unique Protocol Identification Number
NCT05647096
Brief Title
Safety, Tolerability and Performance of the NucleoCapture Device in the Reduction of Circulating cfDNA/NETs in Subjects With Sepsis
Acronym
NUC-CAP
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

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
August 1, 2023 (Anticipated)
Primary Completion Date
May 5, 2025 (Anticipated)
Study Completion Date
May 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Santersus AG
Collaborators
ISS AG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Respiratory Failure
Keywords
Sepsis, Respiratory failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NucleoCapture Treatment
Arm Type
Experimental
Arm Description
Participants in the NucleoCapture treatment arm will receive Standard of Care plus three treatment sessions with the NucleoCapture treatment device. The device consists of 100ml NucleoCapture selective adsorber.
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Participants in the Standard of Care arm will receive standard medical care alone.
Intervention Type
Device
Intervention Name(s)
NucleoCapture device
Intervention Description
100ml NucleoCapture selective DNA adsorber
Primary Outcome Measure Information:
Title
To demonstrate the NucleoCapture column reduces the amount of cfDNA/NETs in the plasma of participants with sepsis and respiratory failure
Description
The mean reduction of an expected ≥50% of the net amount of cfDNA/NETs across the NucleoCapture column at the end of each NuceoCapture treatment session
Time Frame
Within 6 hours from the baseline (pre-column) plasma
Secondary Outcome Measure Information:
Title
Mean reduction in circulating cfDNA/NETs measured by circulating blood levels of nucleosomes (H.3.1)
Description
Mean relative reduction of circulating blood cfDNA/NETs at the end of a complete treatment session with NucleoCapture compared to the change in the mean levels of cfDNA/NETs over a 6 hour period in the SOC treatment arm
Time Frame
Before and after treatment with the NucleoCapture column and at the start and end of a 6 hour period in the SOC treatment arm
Title
The clinical benefit of the NucleoCapture column in participants with sepsis and respiratory failure
Description
Change in organ support and survival
Time Frame
From date of randomisation to day 21 for organ support and day 28 for survival
Other Pre-specified Outcome Measures:
Title
The biological efficacy and performance of NucleoCapture will be assessed using routine biomarkers
Description
Routine organ function, haematology, coagulation and inflammation biomarkers will be measured
Time Frame
At baseline, days 1 to 5, day 7 and day 14
Title
The biological efficacy and performance of NucleoCapture will be assessed using non-routine biomarkers
Description
Non-routine biomarkers of inflammation and coagulation will be measured
Time Frame
At baseline, days 1 to 5, day 7 and day 14
Title
Device handling and usability
Description
Usability and handling of the device will be assessed in the intervention arm
Time Frame
Day 1 up to day 5

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Emma Barsoum
Phone
+447806820434
Email
eb@santersus.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew Aswani
Organizational Affiliation
Santersus AG
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Bonn
City
Bonn
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Bode
Facility Name
Technical University Dresden
City
Dresden
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Spieth
Facility Name
Hannover Medical School
City
Hannöver
Country
Germany
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Klaus Stahl
First Name & Middle Initial & Last Name & Degree
Julius Schmidt
Facility Name
University of Zurich
City
Zürich
Country
Switzerland
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sascha David
Facility Name
Queen Elizabeth Hospital Birmingham
City
Birmingham
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mansoor Bangash
Facility Name
Royal Infirmary of Edinburgh
City
Edinburgh
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Craven
Facility Name
Liverpool University Hospital
City
Liverpool
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ben Morton
Facility Name
Guy's and St Thomas' Hospital
City
London
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marlies Ostermann
First Name & Middle Initial & Last Name & Degree
Duncan Wyncoll
Facility Name
University College London
City
London
Country
United Kingdom
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Brealey
First Name & Middle Initial & Last Name & Degree
Mervyn Singer

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Safety, Tolerability and Performance of the NucleoCapture Device in the Reduction of Circulating cfDNA/NETs in Subjects With Sepsis

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