Clinical trial NCT05453695: Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI)
Official title: Intravenous DNase I for the Treatment of Sepsis: A Phase I Safety and Feasibility Study in ICU Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Sepsis
Critical Illness
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2022-07-12
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Phase I dose-escalation safety and feasibility of IV DNase I in ICU septic patients.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age of ≥18 years
2. Admitted to the ICU in the last 48 hours
3. Suspected or proven infection as the admitting diagnosis
4. A sequential (sepsis) organ function assessment (SOFA) score of ≥2 above baseline
5. Expected to remain in the ICU for ≥ 72 hours

Exclusion Criteria:

1. No consent/inability to obtain consent from a substitute decision-maker
2. Have other forms of clinically apparent shock, including cardiogenic, obstructive (massive pulmonary embolism, cardiac tamponade, tension pneumothorax), hemorrhagic, neurogenic, or anaphylactic shock
3. Have a significant risk of bleeding as evidenced by one of the following:

   * Surgery requiring general or spinal anesthesia within 24 hours before enrolment
   * The potential need for surgery in the next 24 hours
   * Evidence of active bleeding
   * A history of severe head trauma requiring hospitalization
   * Intracranial surgery, or stroke within three months before the study
   * Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or mass lesions of the central nervous system
   * A history of congenital bleeding diatheses
   * Gastrointestinal bleeding within five weeks before the study unless corrective surgery had been performed
   * Trauma is considered to increase the risk of bleeding
   * Presence of an epidural catheter
   * Need for therapeutic anticoagulation
4. Receiving DNase I by inhalation
5. Terminal illness with a life expectancy of fewer than three months
6. Pregnant and/or breastfeeding

Primary outcomes:
measure: Number of patients recruited per month from the start of the study
timeFrame: up to 24 months
measure: Number of patients who completed the protocol
timeFrame: up to 7 days
Secondary outcomes:
measure: Sequential Organ Failure Assessment (SOFA) score
timeFrame: Baseline to Day 10
measure: Organ support free days
timeFrame: at Day 28
measure: Duration of ICU admission
timeFrame: up to 9 months
measure: Time to Hospital discharge
timeFrame: up to 90 days
measure: Mortality at Day 90
timeFrame: up to day 90
measure: European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score
timeFrame: At day 90
measure: Collection of Research Biomarkers related to inflammation and coagulation
timeFrame: up to day 14
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
Study officials:
References: