Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI)

Phase 1

Recruiting

• Conditions: Sepsis; Critical Illness
• Interventions: Drug: Intravenous DNase I

• Registration Number: NCT05453695
• Lead Sponsor: McMaster University

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.

Study Timeline

• Study First Submitted: 2022-06-24
• Study First Submitted QC: 2022-07-11
• Study First Posted: 2022-07-12
• Study Start: 2023-01-17
• Status Verified: 2025-04
• Primary Completion: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Intravenous DNase I	Intravenous DNase I	We will enroll up to 36 Participants; each is receiving repeated unit doses of DNase I, BID, delivered by IV infusion over 3 or 7 consecutive days (12 +/- 1 hour apart) according to the following dose-escalation schedule with up to 6 Participants per dose panel. * Panel 1: 25 µg/kg, BID for 3 days (cumulative dose: 150 µg/kg) * Panel 2: 25 µg/kg, BID for 7 days (cumulative dose: 350 µg/kg) * Panel 3: 125 µg/kg, BID for 3 days (cumulative dose: 750 µg/kg) * Panel 4: 125 µg/kg, BID for 7 days (cumulative dose: 1750 µg/kg)

Primary Outcome Measures

Name	Time	Method
Number of patients recruited per month from the start of the study	up to 24 months	Number of patients recruited per month
Number of patients who completed the protocol	up to 7 days	The ability to complete study infusion and blood collection as prescribed

Secondary Outcome Measures

Name	Time	Method
Time to Hospital discharge	up to 90 days	Time elapsed between enrolment into the study (at admission), and discharge
European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score	At day 90	Average or median EQ-5D-5L score
Collection of Research Biomarkers related to inflammation and coagulation	up to day 14	Number of patients with all sets of biomarkers
Duration of ICU admission	up to 9 months	Number of days since admission to discharge from the ICU
Sequential Organ Failure Assessment (SOFA) score	Baseline to Day 10	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
Organ support free days	at Day 28	Increase of three or more days free from vasopressor therapy, invasive mechanical ventilation or renal replacement therapy.
Mortality at Day 90	up to day 90	Number of patients alive at day 90

Trial Locations

Locations (1)

Hamilton Health Sciences; 🇨🇦 Hamilton, Ontario, Canada