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

Sepsis Clinical Trial

— 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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05647096
• Other study ID #: SAN/01/2022
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 1, 2024
• Est. completion date: May 28, 2026

Study information

• Verified date: April 2023
• Source: Santersus AG
• Contact: Emma Barsoum
• Phone: +447806820434
• Email: eb[@]santersus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 73
• Est. completion date: May 28, 2026
• Est. primary completion date: May 5, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Respiratory Failure
• Respiratory Insufficiency
• Sepsis
• Toxemia

Intervention

Device:
• NucleoCapture device
100ml NucleoCapture selective DNA adsorber

Locations

Country	Name	City	State
Germany	University of Bonn	Bonn
Germany	Technical University Dresden	Dresden
Germany	Hannover Medical School	Hannöver
Switzerland	University of Zurich	Zürich
United Kingdom	Queen Elizabeth Hospital Birmingham	Birmingham
United Kingdom	Royal Infirmary of Edinburgh	Edinburgh
United Kingdom	Liverpool University Hospital	Liverpool
United Kingdom	Guy's and St Thomas' Hospital	London
United Kingdom	University College London	London

Sponsors (2)

Lead Sponsor	Collaborator
Santersus AG	ISS AG

Countries where clinical trial is conducted

Germany,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Device handling and usability	Usability and handling of the device will be assessed in the intervention arm	Day 1 up to day 5
Primary	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	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
Secondary	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