Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients.
In sepsis, the release of 'neutrophil extracellular traps' (NETs) by activated neutrophils may contribute to organ damage by acting as scaffolds that trap blood cells and fibrin clots. Excessive NET formation can occlude the vasculature, promoting thrombosis and tissue hypoperfusion. This is a trial on a novel IV therapy for septic patients that shows promise in multiple animal models of sepsis. The therapy, DNase I, is an enzyme that helps to dismantle NETs by digesting cell-free DNA (cfDNA), the major structural component of NETs. The objective of this study is to conduct a Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients. The results of this study may justify a future Phase II trial of the efficacy and safety of DNase I for critically ill patients with sepsis. This trial proposes 1. \- To determine the safety, feasibility and maximum tolerated dose (MTD) of using DNase I in septic patients 2. \- To evaluate clinical endpoints common in the critically ill such as organ dysfunction severity and trajectory, ICU length of stay, and mortality. 3. \- To describe the effects of DNase I on blood coagulation and NETs release 4. \- To collect samples for future studies on coagulation and immune function in sepsis.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Dose-escalating intravenous infusion of DNase I
Hamilton Health Sciences
Hamilton, Ontario, Canada
RECRUITINGNumber of patients recruited per month from the start of the study
Number of patients recruited per month
Time frame: up to 24 months
Number of patients who completed the protocol
The ability to complete study infusion and blood collection as prescribed
Time frame: up to 7 days
Sequential Organ Failure Assessment (SOFA) score
Quantitative variable: Maximal score of SOFA (Sequential Organ Failure Assessment) will be recorded; Value range 0-24 points * Delta SOFA score, defined as maximum versus minimum SOFA during ICU stay * Change in SOFA score within 48 hours
Time frame: Baseline to Day 10
Organ support free days
Increase of three or more days free from vasopressor therapy, invasive mechanical ventilation or renal replacement therapy.
Time frame: at Day 28
Duration of ICU admission
Number of days since admission to discharge from the ICU
Time frame: up to 9 months
Time to Hospital discharge
Time elapsed between enrolment into the study (at admission), and discharge
Time frame: up to 90 days
Mortality at Day 90
Number of patients alive at day 90
Time frame: up to day 90
European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score
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Average or median EQ-5D-5L score
Time frame: At day 90
Collection of Research Biomarkers related to inflammation and coagulation
Number of patients with all sets of biomarkers
Time frame: up to day 14