Intravenous DNase I for the Treatment of Sepsis (IDEALSepsisI)

Sepsis Clinical Trial

— IDEALSepsisI  

Official title:

Intravenous DNase I for the Treatment of Sepsis: A Phase I Safety and Feasibility Study in ICU Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05453695
• Other study ID #: IDEALSepsisI
• Status: Recruiting
• Phase: Phase 1
• Start date: January 17, 2023
• Est. completion date: September 2025

Study information

• Verified date: March 2024
• Source: McMaster University
• Contact: Alison Fox-Robichaud, MD
• Phone: 905 521 2100
• Email: afoxrob[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: September 2025
• Est. primary completion date: April 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Illness
• Sepsis
• Toxemia

Intervention

Drug:
• Intravenous DNase I
Dose-escalating intravenous infusion of DNase I

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences	Hamilton	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients recruited per month from the start of the study	Number of patients recruited per month	up to 24 months
Primary	Number of patients who completed the protocol	The ability to complete study infusion and blood collection as prescribed	up to 7 days
Secondary	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	Baseline to Day 10
Secondary	Organ support free days	Increase of three or more days free from vasopressor therapy, invasive mechanical ventilation or renal replacement therapy.	at Day 28
Secondary	Duration of ICU admission	Number of days since admission to discharge from the ICU	up to 9 months
Secondary	Time to Hospital discharge	Time elapsed between enrolment into the study (at admission), and discharge	up to 90 days
Secondary	Mortality at Day 90	Number of patients alive at day 90	up to day 90
Secondary	European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D-5L) Utility Score	Average or median EQ-5D-5L score	At day 90
Secondary	Collection of Research Biomarkers related to inflammation and coagulation	Number of patients with all sets of biomarkers	up to day 14