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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Respiratory Failure
• Intervention / Treatment: Device: NucleoCapture device

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.

• Study Type: Interventional
• Enrollment (Estimated): 73
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Emma Barsoum; Phone Number: +447806820434; Email: eb@santersus.com

Study Locations

• Germany
  • Bonn, Germany
    • University of Bonn
    • Contact: Christian Bode
  • Dresden, Germany
    • Technical University Dresden
    • Contact: Peter Spieth
  • Hannöver, Germany
    • Hannover Medical School
    • Contact: Klaus Stahl
    • Sub-Investigator: Julius Schmidt
• Switzerland
  • Zürich, Switzerland
    • University of Zurich
    • Contact: Sascha David
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital Birmingham
    • Contact: Mansoor Bangash
  • Edinburgh, United Kingdom
    • Royal Infirmary of Edinburgh
    • Contact: Thomas Craven
  • Liverpool, United Kingdom
    • Liverpool University Hospital
    • Contact: Ben Morton
  • London, United Kingdom
    • University College London
    • Contact: David Brealey
    • Sub-Investigator: Mervyn Singer
  • London, United Kingdom
    • Guy's and St Thomas' Hospital
    • Contact: Marlies Ostermann
    • Sub-Investigator: Duncan Wyncoll

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NucleoCapture Treatment; 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.	Device: NucleoCapture device; 100ml NucleoCapture selective DNA adsorber
No Intervention: Standard of Care; Participants in the Standard of Care arm will receive standard medical care alone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Within 6 hours from the baseline (pre-column) plasma

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Before and after treatment with the NucleoCapture column and at the start and end of 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	From date of randomisation to day 21 for organ support and day 28 for survival

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The biological efficacy and performance of NucleoCapture will be assessed using routine biomarkers	Routine organ function, haematology, coagulation and inflammation biomarkers will be measured	At baseline, days 1 to 5, day 7 and day 14
The biological efficacy and performance of NucleoCapture will be assessed using non-routine biomarkers	Non-routine biomarkers of inflammation and coagulation will be measured	At baseline, days 1 to 5, day 7 and day 14
Device handling and usability	Usability and handling of the device will be assessed in the intervention arm	Day 1 up to day 5

Collaborators and Investigators

• Sponsor: Santersus AG
• Collaborators: ISS AG
• Investigators: Principal Investigator: Andrew Aswani, Santersus AG

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): May 5, 2026
• Study Completion (Estimated): May 28, 2026

Study Registration Dates

• First Submitted: December 3, 2022
• First Submitted That Met QC Criteria: December 3, 2022
• First Posted (Actual): December 12, 2022

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Sepsis; Respiratory failure
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Respiratory Insufficiency
• Other Study ID Numbers: SAN/01/2022

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No