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

Overview

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.

Interventions

• Device NucleoCapture device
  100ml NucleoCapture selective DNA adsorber

Primary outcome measures

• To demonstrate the NucleoCapture column reduces the amount of cfDNA/NETs in the plasma of participants with sepsis and respiratory failure [Time frame: Within 6 hours from the baseline (pre-column) plasma]

Secondary outcome measures (2)

• Mean reduction in circulating cfDNA/NETs measured by circulating blood levels of nucleosomes (H.3.1) [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]
• The clinical benefit of the NucleoCapture column in participants with sepsis and respiratory failure [Time frame: From date of randomisation to day 21 for organ support and day 28 for survival]

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)

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United Kingdom · 5 centers

• Queen Elizabeth Hospital Birmingham — Birmingham
• Royal Infirmary of Edinburgh — Edinburgh
• Liverpool University Hospital — Liverpool
• Guy's and St Thomas' Hospital — London
• University College London — London

Germany · 3 centers

• University of Bonn — Bonn
• Technical University Dresden — Dresden
• Hannover Medical School — Hannover

Switzerland · 1 center

• University of Zurich — Zurich

Identifiers

NCT: NCT05647096 · SAN/01/2022

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗