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

Обзор

This is a single-centre, randomised-controlled, open-label, feasibility 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 patients with severe acute pancreatitis.

Подробное описание

This study investigates the safety, tolerability and performance of the NucleoCapture extracorporeal apheresis device in patients with acute pancreatitis. Acute pancreatitis is one of the leading gastrointestinal disorders that require urgent clinical care and is increasing in incidence.

cfDNA/NET therapeutic apheresis with NucleoCapture is indicated for the treatment of diseases in which excessive levels of cfDNA/NETs are found, such as acute pancreatitis. Participants will be randomised to receive either standard of care (SOC) alone or SOC plus NucleoCapture treatment. SOC will be according to the current guidelines described by the European Society of Intensive Medicine (ESICM). 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 will take place for all participants whilst in the Intensive Care Unit (ICU) on days 1 to 5, 7, 14, 21 and 28, and at 90 days post discharge to ward-based care. 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 and a patient reported outcome assessment (PROM) 90 days post discharge to ward-based care.

Вмешательства

• Устройство NucleoCapture device
  100ml NucleoCapture selective DNA adsorber.

Первичные конечные точки

• The amount of cfDNA/NETs in the plasma of patients with severe acute pancreatitis after each NucleoCapture treatment. [Срок оценки: Within 6 hours from the baseline once 4.5 plasma volumes has been treated.]

Вторичные конечные точки (5)

• The amount of cfDNA/NETs in the circulating blood in patients after treatment with NucleoCapture compared to standard of care. [Срок оценки: Within 6 hours from the baseline once 4.5 plasma volumes has been treated.]
• Change in organ in support [Срок оценки: From date of randomisation to Day 5]
• 28-day survival [Срок оценки: 28 days]
• ICU length of stay [Срок оценки: Up to 28 days.]
• Hospital length of stay [Срок оценки: Up to 28 days]

Критерии участия

Критерии включения

• Adult patients aged 18 or over
• Acute pancreatitis (following revised Atlanta definition of 2 out of typical pain, serum amylase >3x normal range and/or CT/MRI imaging consistent with pancreatitis)
• Any aetiology
• Acute respiratory (PaO2/FiO2 <300), cardiovascular (systolic BP <90 or any inotropic therapy) or renal failure (serum creatinine >170 µmol/l, or deterioration of >50% eGFR if pre-existing renal disease or urine output <0.5ml/kg/hr for 3 consecutive hours) presenting at any point during the index admission and persistent after 12 h of fluid resuscitation, but for not more than 72 hours
• 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).

Критерии исключения

• The use of other non-routine extracorporeal 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 cardiac index <2.2 L/min/m2 if measured

• Use of dobutamine, epinephrine, phosphodiesterase inhibitors or levosimendan
• Coagulopathy as defined by Platelet count <50x10\^9/L
• Calculated Plasma Volume greater than 5000ml as determined by the following formula:

Vplasma = Vblood x (1 - haematocrit)

Where:

Vplasma = PV Vblood = an estimation of total blood volume (TBV; according to Nadler's formula, incorporating height, weight and sex).

A TBV calculator is available at https://www.omnicalculator.com/health/blood-volume

• Known liver cirrhosis (histologically proven or clinically suspected)
• Active bleeding
• Known citrate intolerance if citrate is required for therapeutic apheresis
• Known heparin allergy if heparin is required for therapeutic apheresis
• Known metastatic disease with life expectancy of <12 months and ECOG score of at least 2
• Known haematological malignancy if not in remission
• Known solid organ transplant and concomitant use of immunosuppression
• Known long term oxygen therapy or Home oxygen use
• Dialysis dependent Chronic Kidney Disease (CKD Stage 5-D)
• Planned or impending dialysis
• Prior use of cardiopulmonary resuscitation (CPR) in current admission
• Requirement for extracorporeal membrane oxygenation (ECMO)
• Patient expected to die within 48 hours of admission to ICU
• Known allergy to components of NucleoCapture (Sepharose beads and linker histone H1.3)
• Pre-existing disease of the exocrine pancreas including chronic pancreatitis, recurrent acute pancreatitis, pancreatic malignancy and/or history of pancreatic surgery
• Chronic neuromuscular disease affected breathing
• Current Participation in another interventional clinical study
• Pregnancy (as established by the presence of beta human chorionic gonadotropin in urine or blood)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 1 центр

• Liverpool University Hospitals NHS Foundation Trust — Liverpool

Идентификаторы

NCT: NCT06566638 · LHS0096

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗